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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -73 مورد

Risk factors for gastric cancer

Risk factors for gastric cancer
Authors:
Annie On On Chan, MD
Benjamin CY Wong, DSc, MD, PhD
Section Editor:
Rachna T Shroff, MD, MS, FASCO
Deputy Editor:
Sonali M Shah, MD
Literature review current through: Apr 2025. | This topic last updated: Jan 06, 2025.

INTRODUCTION — 

Gastric cancer has significant geographic, ethnic, and socioeconomic differences in distribution. This topic review will discuss risk factors for gastric cancer. Epidemiologic aspects are presented separately. (See "Epidemiology of gastric cancer".)

There are two main histologic variants of gastric adenocarcinoma. The most frequent is the "intestinal type," so called because of its morphologic similarity to adenocarcinomas arising in the intestinal tract. The less common "diffuse type" gastric cancers are characterized by a lack of intercellular adhesions, which leaves them unable to form glandular structures. In patients with the inherited form of diffuse-type gastric cancer, the absence of intercellular adhesions is caused by a germline pathogenic variant in the cadherin-1 (CDH1) or alpha-1 catenin (CTNNA1) genes. (See 'Diffuse gastric and lobular breast cancer syndrome' below.)

Although several risk factors are described, Helicobacter pylori infection and family history of gastric cancer are the two main risk factors for gastric cancer. This topic will review the major risk factors for gastric cancer. A more in-depth discussion on the link between H. pylori and gastrointestinal tract malignancy is provided separately. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Gastric malignancy'.)

PRECURSOR LESIONS — 

The sequence of molecular events that underlies intestinal type gastric cancer and its well-defined precursor lesions is incompletely understood. In comparison, much more is known about the molecular pathogenesis of diffuse-type gastric cancers, which display a prominent molecular abnormality in the cadherin-1 (CDH1) gene. (See "Gastric cancer: Pathology and molecular pathogenesis", section on 'The preneoplastic cascade'.)

Intestinal-type cancer — One model for intestinal type gastric cancer describes a progression from chronic gastritis to chronic atrophic gastritis, to intestinal metaplasia, to dysplasia, and eventually, to adenocarcinoma [1,2].

●Longstanding chronic superficial gastritis caused by chronic H. pylori infection, pernicious anemia, or possibly, a high-salt diet leads eventually to chronic atrophic gastritis and intestinal metaplasia.

●Gastric atrophy is accompanied by a loss of parietal cell mass and therefore a reduction in acid production (hypochlorhydria or achlorhydria), a decrease in luminal ascorbic acid (vitamin C) levels, and a compensatory increase in serum gastrin, a potent inducer of gastric epithelial cell proliferation.

Similarly, gastric resection results in hypochlorhydria or achlorhydria, secondary hypergastrinemia, and bile reflux, especially after a Billroth II anastomosis. The increase in gastric pH would permit colonization of bacteria capable of converting dietary nitrates into potent mutagenic N-nitroso compounds.

●Chronic inflammation results in epithelial cell damage with increased free radical generation, a further reduction in luminal ascorbic acid levels, and increased cell turnover.

Atrophic gastritis — Atrophic gastritis is an autoimmune disorder that is characterized by progressive atrophy of the glandular epithelium with loss of parietal and chief cells. The loss of the normal exocrine glands of the gastric mucosa causes hypochlorhydria (a decrease in hydrochloric acid) and a resultant increase in gastric pH. An abnormally high pH in the stomach permits microbial colonization, some of which possess nitrate reductase, allowing nitrosation that is genotoxic. In addition, there is a loss of endocrine cells, which normally secrete epidermal and transforming growth factors, thereby aiding the stomach in regenerating damaged tissue. Populations with a high prevalence of atrophic gastritis also have a high prevalence of gastric cancer and vice versa [3].

Atrophic gastritis and other conditions that cause gastric atrophy are associated with an increased risk of both cardia and noncardia gastric adenocarcinomas (figure 1). The magnitude of the risk is variable in the literature, with estimates ranging from 3 to 18 times greater than an age-matched population. This subject is discussed in detail separately. (See "Metaplastic (chronic) atrophic gastritis", section on 'Gastric adenocarcinomas'.)

Intestinal metaplasia and dysplasia — Metaplasia is a potentially reversible change from one fully differentiated cell type to another, a process of adaptation to environmental stimuli. The most common form of metaplasia in the stomach is the intestinal type (picture 1). It occurs as a result of H. pylori infection or bile reflux, or it can be induced experimentally with irradiation [4,5]. Intestinal metaplasia is more frequent in countries with a higher incidence of gastric carcinoma [6], and at least in experimental animal models, it precedes the development of gastric carcinoma [7]. (See "Gastric cancer: Pathology and molecular pathogenesis", section on 'Intestinal metaplasia' and "Gastric cancer: Pathology and molecular pathogenesis", section on 'Gastric dysplasia'.)

An approach to patients with intestinal metaplasia is presented separately. (See "Metaplastic (chronic) atrophic gastritis".)

Data from humans also provide support for the concept of intestinal metaplasia as a precursor lesion for intestinal type gastric cancer. A study from Japan found that the presence of intestinal metaplasia was the only criterion associated with the development of intestinal type gastric cancer [8]. In China, intestinal metaplasia was found in 33 percent of the population in a high-prevalence area of gastric cancer, and dysplasia, common in the lesser curvature of the body and in the incisura, was found in 20 percent [9].

Most patients diagnosed with high-grade dysplasia of the gastric mucosa either already have or will soon develop gastric cancer. In gastrectomy specimens for gastric cancer, 20 to 40 percent of patients have associated dysplasia [10]. Rates of progression from dysplasia to gastric cancer have been estimated at 21, 33, and 57 percent of cases of mild, moderate, and severe dysplasia, respectively [10].

The absolute magnitude of risk conferred by intestinal metaplasia and dysplasia was addressed in a report from Sweden that included 405,172 patients with gastric biopsy samples taken for a non-malignant indication between 1979 and 2011 [11]. The risk of gastric cancer was significantly increased in the presence of intestinal metaplasia (hazard ratio [HR] 6.2, 95% CI 4.7-8.2) and dysplasia (HR 10.9, 95% CI 7.7-15.4). It was estimated that approximately 1 in 39 patients with intestinal metaplasia and 1 in 19 with dysplasia would develop gastric cancer within 20 years.

Diffuse-type cancers — In contrast to intestinal type gastric cancers, diffuse-type gastric cancers have no clearly defined precancerous lesion. Diffuse-type gastric cancer is discussed separately. (See "Gastric cancer: Pathology and molecular pathogenesis", section on 'Intestinal versus diffuse types'.)

ENVIRONMENTAL RISK FACTORS — 

There are geographic and ethnic differences in the incidence of gastric cancer around the world, as well as trends in each population over time. Emigrants from high-incidence to low-incidence countries often experience a decreased risk of developing gastric carcinoma. Such findings strongly suggest that environmental factors have an important role in the etiology of gastric cancer and that exposure to risk factors occurs early in life. (See "Epidemiology of gastric cancer".)

Helicobacter pylori — The World Health Organization's International Agency for Research on Cancer (IARC) classified H. pylori as a group 1 or definite carcinogen [12]. As noted above, intestinal-type gastric carcinoma is believed to evolve as a progression from atrophy to metaplasia, to dysplasia, and then to carcinoma. The most common cause of gastritis is H. pylori (picture 2).

Four sources of evidence support an association between H. pylori infection and gastric cancer: epidemiologic studies comparing prevalence rates of gastric cancer and H. pylori infection, cross-sectional studies evaluating H. pylori infection in patients with gastric cancer, prospective studies associating H. pylori infection with gastric cancer, and clinical trials demonstrating a significantly reduced incidence of gastric cancer after eradication of H. pylori. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Gastric malignancy'.)

It is thought that H. pylori infection triggers inflammation at the corpus mucosa, which results in atrophy and intestinal metaplasia. H. pylori infection has been associated with an approximately sixfold increase in the risk of adenocarcinomas distal to the cardia, including both the intestinal and diffuse types. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Gastric malignancy' and "Gastric cancer: Pathology and molecular pathogenesis", section on 'Helicobacter pylori'.)

A paradox in H. pylori infection is that divergent clinical outcomes occur: some patients develop a duodenal ulcer or gastric cancer, while the majority have no significant clinical symptoms. Bacterial virulence factors alone have not adequately explained why the ulcer or the gastric cancer phenotype develops. Ongoing studies are helping to elucidate the basis for these varying outcomes. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Pathophysiology and immune response'.)

Diet

Salt and salt-preserved foods — Substantial evidence from ecologic, case-control, and cohort studies strongly suggests that the risk of gastric cancer increases with a high intake of salt and various traditional salt-preserved foods, such as salted fish, cured meat, and salted or pickled vegetables [13-22]. In 2007, salt and salted/salty foods were classified as probable risk factors for gastric cancer [23].

A potential synergistic effect of salt and H. pylori has also been described [17,20,22,24], although not in all studies [18]. High salt intake damages stomach mucosa and increases the susceptibility to carcinogenesis in rodents [25-27]. The induced proliferative change may act to promote the effect of food-derived carcinogens.

The declining incidence of gastric cancer worldwide over the last 50 years has been attributed, at least in part, to the spread of refrigeration [28], the use of which would inversely correlate with salting and other salt-based methods of preservation, such as curing, smoking, and pickling, and with the overall volume of salt in the diet. (See "Epidemiology of gastric cancer".)

Nitroso compounds — Humans are exposed to N-nitroso compounds (compounds containing an -NO group) from diet, tobacco smoke, and other environmental sources, as well as from endogenous synthesis, which contributes to 40 to 75 percent of total exposure [29]. N-nitroso compounds are generated after consumption of nitrates, which are natural components of foods like vegetables and potatoes and are used as a food additive in some cheeses and cured meats. Dietary nitrates are absorbed in the stomach and secreted in saliva in a concentrated form, where they are reduced to nitrites by oral bacteria. Nitrites can also react with nitrosatable compounds, such as amines, amides, and amino acids, to form N-nitroso compounds.

The evidence linking N-nitroso compounds to gastric cancer is as follows:

●Elevated levels of gastric nitrite, particularly in a high-pH environment, have been linked to advanced precancerous gastric lesions [30].

●The risk of gastric cancer associated with dietary intake of nitrites and nitrosodimethylamine (NDMA), and endogenous formation of nitroso compounds was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study [31]. While there was no association between intake of nitrites/NMDA and gastric cancer risk, endogenous production of N-nitroso compounds was significantly associated with noncardia cancer risk (hazard ratio [HR] 1.42, 95% CI 1.14-1.78).

●Diets that are high in fried food, processed meat, fish, and alcohol (and low in vegetables, fruits, milk, and vitamin A) have been associated with an increased risk of gastric carcinoma in several epidemiologic studies [16,32,33]. A meta-analysis estimated that the relative risk of gastric cancer associated with consumption of 30 g of processed meat per day (approximately one-half of an average serving) was 1.15 (95% CI 1.04-1.27) [34]. The risk of noncardia gastric cancer was particularly increased by red and processed meat consumption among H. pylori-positive individuals in a large, prospective nutrition survey [32].

In 2015, the World Health Organization's IARC reviewed the evidence linking intake of processed meat with a variety of cancer sites and concluded that there was a positive association between consumption of processed meat and stomach cancer [35]. A majority of the working group concluded that there was sufficient evidence in human beings for the carcinogenicity of consuming processed meat. Processed meats (eg, sausages, bacon, ham, beef jerky, corned beef, and other smoked, salted, fermented, or cured meats) were classified as group 1 carcinogens, placing these foods in the same risk category for cancer as asbestos, cigarettes, and alcohol (although the amount of increased risk is nowhere near the same).

Low folate levels — A meta-analysis of epidemiology studies found an inconsistent association between low levels of folate and the risk of gastric cancer [36].

Obesity — Excess body weight is associated with an increased risk of gastric cancer [37-39]. In a meta-analysis of cohort studies identifying 9492 gastric cancer cases, excess body weight (defined as a body mass index [BMI] ≥25 kg/m2) was associated with an increased risk of gastric cancer (odds ratio [OR] 1.22, 95% CI 1.06-1.41) [37]. The strength of the association increased with increasing BMI. Whether this risk extends to all stomach sites is not clear. An updated 2016 analysis of observational studies on cancer risk and excess body fat conducted by a working group of the IARC concluded that the data were sufficient for gastric cardia cancers (relative risk for the highest BMI category evaluated versus a normal BMI 1.8, 95% CI 1.3-2.5) but not for gastric noncardia cancers [39].

Smoking — Several studies have examined the relationship between tobacco smoking and gastric cancer. A meta-analysis of 42 studies estimated that the risk was increased approximately 1.53-fold and was higher in men [40]. A prospective study from Europe (EPIC) found a similar magnitude of risk, which diminished after 10 years of smoking cessation [41]. Approximately 18 percent of gastric cancer cases were attributed to smoking. Smoking tobacco increases the risk of gastric cancer, in part, by potentiating the carcinogenic effect of infection with CagA-positive H. pylori [42-45].

Occupational exposures — There is some evidence that occupations in coal and tin mining, metal processing (particularly steel and iron), and rubber manufacturing industries lead to an increased risk of gastric cancer; however, the data are disparate [46-49].

Influence of salt and intake of salted foods — As noted above, there is a link between intake of salt and highly salted foods and gastric cancer risk; high salt intake damages stomach mucosa and increases the susceptibility to carcinogenesis.

The consumption of salted food appears to increase the possibility of persistent infection with H. pylori [50,51]. In addition, a synergistic interaction between H. pylori infection and salted food intake that increases the risk of gastric cancer has also been reported in some [17,52,53], but not all [18], case-control studies. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Acquisition'.)

There may be a protective effect of nonsteroidal anti-inflammatory drug (NSAID) use. (See 'NSAIDs' below.)

Epstein-Barr virus — Infection with Epstein-Barr virus (EBV) is associated with a number of malignancies, especially nasopharyngeal carcinoma. (See "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma", section on 'Epstein-Barr virus' and "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma", section on 'Etiology and risk factors'.)

A possible role in gastric cancer was initially suggested in a study from Korea in which evidence of EBV was found in the tumor cells of 12 of 89 (13 percent) gastric carcinoma patients compared with none of 27 controls with a benign ulcer or any of the benign tissues from the cases [54]. Some of the tumor cells had a histologic appearance similar to that of nasopharyngeal carcinoma.

Since then, it has been estimated that between 5 and 10 percent of gastric cancers worldwide are associated with EBV [55,56]. EBV-associated gastric cancers are characterized by DNA methylation of the promoter region of various cancer-associated genes, which silences the expression of these genes [57-62]. How this leads to gastric cancer is unclear, but silencing the expression of certain genes may modulate the latent-lytic switch of EBV infection, allowing the virus to escape immune detection and remain dormant within the host cells [63].

EBV-associated gastric cancers have distinct clinicopathologic characteristics, including male predominance, preferential location in the gastric cardia or postsurgical gastric stump, lymphocytic infiltration, a lower frequency of lymph node metastasis, perhaps a more favorable prognosis [57,59,64-67], and a diffuse type of histology in most [57,59,60,67,68], but not all [63-65], series. (See "Gastric cancer: Pathology and molecular pathogenesis", section on 'Epstein-Barr virus-associated gastric cancer'.)

Alcohol — A consistent association between alcohol consumption and the risk of gastric cancer has not been demonstrated [69-72]. A strong correlation between alcohol consumption (especially beer) and gastric cancer risk has been reported [73]. At least one European study suggests that daily intake of wine may be protective [69].

Socioeconomic status — The risk of distal gastric cancer is increased by approximately twofold in populations with low socioeconomic status [74-77]. By contrast, proximal gastric cancers have been associated with higher socioeconomic class [78].

Gastric surgery — There is an increased risk of gastric cancer after gastric surgery, with reported frequency ranging from less than 1 to 9 percent [79-81]. Both the risk and the interval between initial gastric surgery and the development of remnant gastric cancer depends on the reason for the initial surgery and the type of reconstruction [82-85]:

●The Billroth II procedure (gastrojejunostomy) carries a higher risk than the Billroth I procedure (gastroduodenostomy) [81,83,85,86]. Although the exact cause of the increased risk is unknown, it is thought to be due to regurgitation of alkaline bile and pancreatic juice (which is greater after a Billroth II procedure compared with a Billroth I procedure). (See "Partial gastrectomy and gastrointestinal reconstruction", section on 'Gastrointestinal reconstruction'.)

●The risk of gastric cancer also increases with longer duration of follow-up after gastric surgery (typically 15 to 25 years) [81,83,85-89].

●The interval between initial gastric surgery and the development of remnant gastric cancer is longer if the original surgery was done for benign disease versus gastric cancer (mean 30 versus 12 years in one series [85]) and if the gastric reconstruction is a Billroth II versus a Billroth I procedure (mean 32 versus 12 years in the same series).

Cancer survivors who received abdominal irradiation — An elevated risk of gastric cancer has been reported in adult survivors of testicular cancer and Hodgkin lymphoma and in childhood cancer survivors who received abdominal radiation therapy [90]. An especially high risk has been noted in Hodgkin lymphoma survivors who received both subdiaphragmatic radiation therapy and high-dose procarbazine (OR 77.5, 95% CI 14.7-1452) [91]. (See "Second malignancies after treatment of classic Hodgkin lymphoma", section on 'Gastrointestinal cancers'.)

Possible protective factors

Fruits, vegetables, and fiber — Consumption of fruits and vegetables (particularly fruit) is probably protective against gastric cancer [13]. Case-control studies from Europe, Asia, and North America and a pooled analysis of multiple such studies have consistently found intake of fruits and vegetables to be protective against gastric cancer, reducing the risk by approximately 30 to 40 percent for both fruits and vegetables for the highest versus lowest categories of intake [92-97]. Some studies suggest that diets low in citrus fruit show the strongest association with gastric carcinoma [98].

Cohort studies have been less consistent. A meta-analysis of 17 studies found a weaker overall association in the reduction of gastric cancer risk from high intake of fruits (summary relative risk 0.90, 95% CI 0.83-0.98), but there was no discernible protective effect from vegetables (summary relative risk 0.96, 95% CI 0.88-1.06) [99].

The protection afforded by vegetables and fruits is most likely related to their vitamin C content, which is thought to reduce the formation of carcinogenic N-nitroso compounds inside the stomach. Cooked vegetables do not show the same protective effect as uncooked vegetables [100].

Dietary fiber may reduce the risk of gastric cancer. In a meta-analysis, the summary OR for the highest versus lowest intake of dietary fiber was 0.58 (95% CI 0.49-0.67) [101]. The association was similar for different fiber sources and types, and for diffuse-type (OR 0.62, 95% CI 0.42-0.92) and intestinal-type gastric cancer (OR 0.63, 95% CI 0.45-0.89). In contrast to these results, the prospective EPIC-EURGAST study found that cereal fiber (but not other types of fiber) had a strong protective role for diffuse-type gastric cancer but not intestinal type gastric cancer [102]. Further study on different food sources of fiber in relation to gastric cancer risk is warranted to confirm these relationships.

NSAIDs — Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with the risk of distal gastric adenocarcinoma [103,104], and there may be an interaction between NSAID use and H. pylori infection. (See 'Helicobacter pylori' above.)

A retrospective study looked at 52,161 patients who had been hospitalized with peptic ulcer disease [103]. On multivariate analysis, regular NSAID use was an independent protective factor against the development of gastric cancer (HR 0.79 for each year of NSAID use), and the protective effect was most pronounced in patients with a history of H. pylori infection (HR 0.52 for each incremental year).

Reproductive hormones — Gastric cancer incidence rates are consistently lower in women than in men in both high- and low-risk regions worldwide. There are data that support the hypothesis that reproductive hormones may have a protective role in gastric cancer risk in women [105-107]. One study found that there were associations between age of menopause (HR 0.80 per five-year increase in menopausal age, 95% CI 0.66-0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30 to 36 years of fertility, HR 1.90, 95% CI 1.25-2.90), years since menopause (HR 1.26 per each five years, 95% CI 1.03-1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08-2.39) [105].

HOST-RELATED FACTORS

Familial predisposition — Although most gastric cancers are sporadic, aggregation within families occurs in approximately 10 percent of cases. Truly hereditary (familial) gastric cancer accounts for 1 to 3 percent of the global burden of gastric cancer and comprises several major syndromes: diffuse gastric and lobular breast cancer syndrome (DGLBCS), previously known as hereditary diffuse gastric cancer (HDGC); gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS); and familial intestinal gastric cancer (FIGC). The risk of developing gastric cancer is high in these families [108]. (See 'Diffuse gastric and lobular breast cancer syndrome' below.)

Diffuse gastric and lobular breast cancer syndrome — DGLBCS is an autosomal dominant inherited form of diffuse-type gastric cancer, a highly invasive form of gastric cancer that is characterized by late presentation and a poor prognosis. DGLBCS is characterized by germline pathogenic variant in either the cadherin 1 (CDH1) or alpha-1 catenin (CTNNA1) genes in an isolated individual with diffuse gastric cancer or in a family with one or more cases of diffuse gastric cancer in first- or second-degree relatives [109]. CDH1-related DGLBCS may also be associated with lobular breast cancer and nonsyndromic cleft lip/palate. For patients with CTNNA1-related DGLBCS, the association with breast cancer is less certain, but the term "DGBLCS" is still preferred. (See "Diffuse gastric and lobular breast cancer syndrome", section on 'Terminology'.)

For individuals with (or at risk for) diffuse gastric cancer, guidelines are available for genetic testing for CDH1 and CTNNA1 mutations from the International Gastric Cancer Linkage Consortium. Further details are discussed separately. (See "Diffuse gastric and lobular breast cancer syndrome", section on 'Criteria for genetic testing'.)

GAPPS — Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant cancer predisposition syndrome with a significant risk of gastric adenocarcinoma [110]. The finding of inherited point mutations in exon 1B of the adenomatous polyposis coli (APC) gene reveals this to be a variant of familial adenomatous polyposis (FAP) [111]. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis".)

GAPPS result in fundic gland polyposis (including dysplastic lesions, intestinal-type gastric adenocarcinoma, or both) that is restricted to the proximal stomach, with no evidence of duodenal or colorectal polyposis or another hereditary gastrointestinal cancer syndrome [110,112,113]. Specific pathologic findings associated with GAPPS are discussed separately. (See "Gastric cancer: Pathology and molecular pathogenesis", section on 'Genetic predisposition and hereditary syndromes'.)

This condition is characterized by incomplete penetrance. Very few families with GAPPS have been reported worldwide [110-113]. The age of onset of gastric cancer is variable, and fundic gland polyposis with multifocal dysplasia has been detected as early as 10 years of age [110,113]. The youngest patient with generalized gastric adenocarcinoma presented at the age of 26 years [113].

Familial intestinal gastric cancer — FIGC is a potential diagnosis when histopathologic reports denote intestinal type gastric cancers that segregate within families without gastric polyposis. An autosomal dominant inheritance pattern has been noted in many such families [114]. The genetic cause is unknown, and few recommendations are available for the clinical management of these patients [115].

Other hereditary cancer syndromes — Gastric cancer has also been described in association with certain other inherited cancer syndrome, such as:

●Lynch syndrome (hereditary nonpolyposis colorectal cancer) (see "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Extracolonic manifestations')

●Familial adenomatous polyposis (FAP) (see "Clinical manifestations and diagnosis of familial adenomatous polyposis", section on 'Extracolonic manifestations')

●Li-Fraumeni syndrome (see "Li-Fraumeni syndrome", section on 'Spectrum of malignancies and age at onset')

●Peutz-Jeghers syndrome (see "Peutz-Jeghers syndrome: Clinical manifestations, diagnosis, and management", section on 'Gastrointestinal cancers')

●Juvenile polyposis syndrome (see "Juvenile polyposis syndrome", section on 'Gastrointestinal cancer risk')

●Hereditary breast and ovarian cancer syndrome (see "Overview of hereditary breast and ovarian cancer syndromes" and "Cancer risks in BRCA1/2 carriers", section on 'Other solid tumors')

●Phosphatase and tensin homolog (PTEN) hamartoma tumor (Cowden) syndrome (see "PTEN hamartoma tumor syndromes, including Cowden syndrome", section on 'Gastrointestinal')

●Ataxia-telangiectasia (see "Ataxia-telangiectasia")

These inherited cancer syndromes are rare causes of gastric cancer. However, there is an increased risk of gastric cancer among people with pathogenic variants associated with specific inherited cancer syndromes who are also infected with H. pylori [116]. In an observational cohort study of over 10,000 patients with gastric cancer in Japan, germline pathogenic variants in certain cancer-predisposing genes were associated with an increased risk of gastric cancer [116]; these genes and associated syndromes included APC (FAP), ATM (ataxia-telangiectasia), BRCA1, BRCA2, and PALB2 (hereditary breast and ovarian cancer syndrome), CDH1 (DGLBCS, previously known as HDGC), and MLH1, MSH2, and MSH6 (Lynch syndrome). H. pylori infection also significantly modified the association between these pathogenic variants and the risk of gastric cancer, both for these specific cancer-predisposing genes overall (relative excess risk due to interaction 14.22) and the homologous-recombination genes (ATM, BRCA1, BRCA2, and PALB2; relative excess risk due to interaction 16.01). Carriers of these pathogenic variants who were also infected with H. pylori had a higher lifetime risk of gastric cancer (46 percent) compared with non-carriers infected with H. pylori (14 percent) and carriers not infected with H. pylori (less than 5 percent).

These data suggest that individuals with these pathogenic variants should be tested for H. pylori infection and offered eradication treatment if present. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults".)

Other associations — In some families who appear to have a familial aggregation of gastric cancers but no identifiable inherited syndrome, certain risk factors may explain the association:

●Some of the observed familial risk may be due to clustering of H. pylori infection within families [117]. However, a case-control study found that a family history increased the risk of gastric cancer independently of H. pylori infection [118]. Another case-control study found that a positive history of gastric cancer in one or more first-degree relatives was associated with an increased risk of gastric cancer in women (odds ratio [OR] 5.1) but not in men after controlling for H. pylori infection and other confounding variables [119].

●A genetic predisposition for chronic atrophic gastritis, a precursor of gastric carcinoma, has been described and may account for at least some cases of familial gastric cancer [120]. The genetic segregation analysis showed Mendelian transmission of a recessive autosomal gene, with penetrance dependent on age and the status of chronic atrophic gastritis in the mother. Significantly more patients were affected whose mothers were also affected (48 versus 7 percent).

Importance of Helicobacter pylori infection — There may be a role for screening selected asymptomatic individuals for H. pylori (eg, individuals who are both first-generation immigrants from areas of high gastric cancer incidence and have a first-degree relative with gastric cancer). However, further studies are needed before it can be recommended.

Infection with H. pylori is an important and potentially modifiable risk factor for gastric cancer. (See 'Helicobacter pylori' above.)

In several regions of high gastric cancer incidence, routine screening and eradication of H. pylori has been implemented or is being evaluated to decrease rates of gastric cancer. Limited data suggest that screening for H. pylori in asymptomatic, healthy individuals in areas of high gastric cancer incidence may decrease the risk of gastric cancer. (See "Gastric cancer screening".)

Successful eradication of H. pylori infection in first-degree relatives with gastric cancer has been demonstrated to significantly reduce the risk of a subsequent gastric cancer in areas of high cancer incidence [121]. This was illustrated in a randomized trial in South Korea in which 1838 individuals with H. pylori infection and a first-degree relative with gastric cancer were assigned to receive either eradication therapy or placebo. During a median follow-up of 9.2 years, gastric cancer developed in significantly fewer patients in the H. pylori treatment group as compared with the placebo group, although the overall incidence of gastric cancer in both groups was low (2.7 versus 1.2 percent; hazard ratio [HR] 0.45). Trial participants were not evaluated for genetic susceptibility to gastric cancer or the bacterial virulence of the H. pylori.

In general, in areas of low gastric cancer incidence, there is no role for routine screening of asymptomatic, average-risk, healthy individuals for H. pylori in order to decrease the risk of gastric cancer. There might be a role for screening individuals who are both first-generation immigrants from areas of high gastric cancer incidence and have a first-degree relative with gastric cancer, but additional data are needed. This subject is discussed in more detail separately. (See "Gastric cancer screening", section on 'Helicobacter pylori eradication'.)

Genetic polymorphisms — Certain polymorphisms have been associated with gastric cancer:

●The human interleukin 1 beta (IL-1B) gene is the most important candidate gene in the host that could affect the clinical outcome of H. pylori infection because it is upregulated by infection, profoundly proinflammatory, and the most powerful acid inhibitor known. Polymorphisms in the IL-1B gene (carriers of IL-1B-511*T) and in the IL-1 receptor antagonist gene (IL-1RN*2/*2) have been associated with an increased risk of gastric cancer [122]. Another study showed that polymorphisms (IL-1B-511*T carriers [IL-1B-511*T/*T or IL-1B-511*T/*C]) and H. pylori virulence factors (vacAs1, vacAm1, and cagA positive) were additive in increasing the risk of gastric cancer [123].

●Interferon gamma (IFN-gamma) signaling has an essential role in human H. pylori infection. The IFNGR1 gene encodes chain 1 of the IFN-gamma receptor. Sequencing of IFNGR1 revealed a close association between the 56C>T, H318P, and L450P variants and high H. pylori antibody concentrations [124]. These variants were more prevalent among individuals from a study population from Senegal compared with a study population from Germany. However, as the incidence rates of gastric cancer in individuals from Africa are generally lower than other geographic regions, further clinical data are necessary to explain how variants in IFNGR1 influence H. pylori infection and gastric cancer risk. (See "Epidemiology of gastric cancer", section on 'Global incidence'.)

●Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been associated with gastric cancer, mainly among individuals from Eastern Asia [125].

Gastric polyps — Gastric polyps are typically found incidentally when an upper gastrointestinal endoscopy is performed for an unrelated indication; only rarely do they cause symptoms or other clinical signs. Nevertheless, their discovery can be important since many polyps have malignant potential. (See "Gastric polyps".)

Blood group — The role of genetic factors was first suggested by the study of blood groups and determinants of chronic gastritis [126]. Individuals of blood group A have been known for decades to show an approximately 20 percent excess of gastric cancer compared with those of group O, B, or AB [127-129]. They also show a similar increase in the rate of pernicious anemia. Some data suggest that group A may be particularly associated with diffuse-type gastric cancer [126]. It is possible that the observed associations are not due to the blood group antigens themselves but to the effects of genes closely associated with them.

Hypertrophic gastropathy and immunodeficiency syndromes — Hypertrophic gastropathy (including Ménétrier's disease) [81] and various immunodeficiency syndromes [130,131] have been linked with gastric cancer. However, the strength of these associations remains undefined. (See "Approach to the patient with large gastric folds".)

Gastric ulcer — An association between benign gastric ulcers and gastric cancers probably reflects common risk factors (ie, mainly H. pylori infection) [132-135]. The largest cohort study followed (for an average of nine years) almost 60,000 Swedish patients who had been hospitalized for a gastric or duodenal ulcer [136]. The risk of gastric cancer was increased among patients with benign gastric ulcers (incidence ratio 1.8), was unchanged among patients with prepyloric ulcers, and was decreased among patients with benign duodenal ulcers (incidence ratio 0.6).

In a study from Japan, 1120 patients with peptic ulcer disease who had H. pylori eradication therapy were followed for a mean of 3.4 years [137]. Gastric cancer developed only in patients with a gastric ulcer but not in patients with duodenal ulcers. Patients who developed gastric cancer were significantly more likely to have persistent H. pylori infection (HR 3.4). A follow-up study from the same group showed that in patients with peptic ulcer diseases, the risk of gastric cancer was significantly increased with persistent H. pylori infection, a higher grade of baseline gastric mucosal atrophy, and older age [138].

Pernicious anemia — Pernicious anemia, a sequela of autoimmune chronic atrophic gastritis directed against hydrogen-potassium ATPase in the gastric parietal cells, is associated with an increased risk of intestinal type gastric cancer. A two- to sixfold excess risk has been reported [139-143], but as with other predisposing conditions, the actual degree of risk varies with the duration of disease and geographic location. Pernicious anemia is also associated with an increased risk of gastric neuroendocrine tumors, presumably due to prolonged achlorhydria resulting from parietal cell loss, compensatory hypergastrinemia, and argyrophilic cell hyperplasia [144]. (See "Metaplastic (chronic) atrophic gastritis", section on 'Gastric neuroendocrine (carcinoid) tumors' and "Metaplastic (chronic) atrophic gastritis", section on 'Gastric adenocarcinomas' and "Causes and pathophysiology of vitamin B12 and folate deficiencies", section on 'Pernicious anemia'.)

On the other hand, "iatrogenic" achlorhydria induced by long-term use of histamine 2 receptor antagonists or proton pump inhibitors has not been associated with an increased risk of either gastric adenocarcinomas or neuroendocrine tumors [145-149]. An association between maintenance therapy with omeprazole and the development of atrophic gastritis in individuals with H. pylori infection has been suggested, but the data are inconclusive. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Atrophic gastritis'.)

Although the benefit of screening or surveillance endoscopy in patients with pernicious anemia has not been established, a guideline issued by the American Society for Gastrointestinal Endoscopy (ASGE) recommends the following [150]:

●A single endoscopy should be performed to identify prevalent lesions (carcinoid tumors and gastric cancer).

●There are insufficient data to support subsequent surveillance endoscopy in patients without these findings.

Despite these recommendations, the cost-effectiveness of initial screening endoscopy in patients with pernicious anemia is uncertain. This subject is addressed in detail separately. (See "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency", section on 'Determining the underlying cause of vitamin B12 deficiency'.)

INTERPLAY BETWEEN HOST AND ENVIRONMENTAL FACTORS — 

Several observations have described interplay between host and environmental factors.

●As noted above, higher salt intake correlates with a higher prevalence of persistent H. pylori infection and with a higher risk of gastric cancer in those infected with H. pylori. A possible explanation is that mucosal damage caused by high salt intake facilitates H. pylori infection. The resultant hypochlorhydria and bacterial overgrowth, with the subsequent conversion of nitrites into the mutagenic N-nitrosamines, may then lead to metaplasia, dysplasia, and cancer. (See 'Influence of salt and intake of salted foods' above.)

●The gastric juice of H. pylori-positive individuals had a lower concentration of vitamin C than that of H. pylori-negative individuals, but the concentration returned to normal when the H. pylori was eradicated [151]. As a result, vitamin C may have an important role in preventing the damage caused by H. pylori through its antioxidant effect [151].

●Beta-carotene and ascorbic acid are believed to interfere with progression to cancer through their antinitrosation and antioxidant effects, and thus act as protective factors [152].

●A model of gastric carcinogenesis recognizes the interplay between exogenous risk factors (such as H. pylori or nitroso compounds), endogenous protective factors (such as the ability to repair DNA damage), and exogenous protective factors (such as antioxidants). H. pylori infection in early life leads to chronic inflammation. The resulting cellular proliferation increases the likelihood of mitotic error. Dietary mutagens may also increase the risk of mutation while dietary antioxidants act as protective factors. Because some DNA damage can be self-corrected, H. pylori-related mutations only rarely lead to malignant transformation. Thus, a longer duration of infection, especially infection acquired during childhood and continuing until old age, increases the risk of significant DNA damage with subsequent malignant transformation [152].

●The H. pylori genotype and host genetic polymorphisms have a role in determining the clinical consequences of H. pylori infection and thus the risk of developing gastric cancer. It has been suggested that combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.

SCREENING GUIDELINES — 

Approaches to screening patients for gastric cancer are discussed separately. (See "Gastric cancer screening".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastric cancer".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Stomach polyps (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Risk factors – Several risk factors for gastric cancer have been identified, the most important of which are infection with H. pylori and family history. (See 'Introduction' above.)

●Molecular events leading to gastric cancer and precursor lesions – The sequence of molecular events that underlies intestinal-type gastric cancer and its precursor lesions is incompletely understood. In comparison, much more is known about the molecular pathogenesis of diffuse-type gastric cancers, which display a prominent molecular abnormality in the cadherin-1 (CDH1) and alpha-1 catenin (CTNNA1) genes. (See 'Precursor lesions' above.)

●Interplay between host and environmental factors – Gastric cancer that develops in patients at average risk involves an interplay of bacterial, host, and environmental factors. Dietary (nitroso compounds, high-salt diet with few vegetables) and lifestyle factors (smoking and alcohol consumption) probably account for one-third to one-half of all gastric cancers. Helicobacter pylori infection, especially certain genotypes (vacAs1, vacAm1, and cagA positive), remains an important risk factor. The risk is increased further in hosts who possess specific types of cytokine polymorphisms (IL-1B-511*T/*T or IL-1B-511*T/*C). (See 'Interplay between host and environmental factors' above.)

●Hereditary gastric cancer – Although most gastric cancers are sporadic, aggregation within families occurs in approximately 10 percent of cases. Truly hereditary (familial) gastric cancer accounts for 1 to 3 percent of the global burden of gastric cancer and comprises several major syndromes: diffuse gastric and lobular breast cancer syndrome (DGLBCS), previously known as hereditary diffuse gastric cancer (HDGC), which is due to germline mutations in the CDH1 and CTNNA1 genes; gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS); and familial intestinal gastric cancer (FIGC). The risk of developing gastric cancer is high in these families. (See "Diffuse gastric and lobular breast cancer syndrome".)

Gastric cancer has also been described in association with certain other inherited cancer syndromes, including Lynch syndrome (hereditary nonpolyposis colorectal cancer), familial adenomatous polyposis, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, juvenile polyposis, hereditary breast and ovarian cancer syndrome, and possibly, phosphatase and tensin homolog (PTEN) hamartoma tumor (Cowden) syndrome, but these are all fairly rare causes of gastric cancer. Nevertheless, guidelines for management of individuals affected by these syndromes generally recommend screening for gastric cancer. (See 'Familial predisposition' above.)

ACKNOWLEDGMENT — 

We are saddened by the death of Mark Feldman, MD, MACP, AGAF, FACG, who passed away in March 2024. UpToDate gratefully acknowledges Dr. Feldman's role as Section Editor on this topic and his dedicated and longstanding involvement with the UpToDate program.

  1. Correa P. The gastric precancerous process. Cancer Surv 1983; 2:437.
  2. Correa P. A human model of gastric carcinogenesis. Cancer Res 1988; 48:3554.
  3. Genta RM. Acid suppression and gastric atrophy: sifting fact from fiction. Gut 1998; 43 Suppl 1:S35.
  4. Sobala GM, O'Connor HJ, Dewar EP, et al. Bile reflux and intestinal metaplasia in gastric mucosa. J Clin Pathol 1993; 46:235.
  5. Watanabe H. Experimentally induced intestinal metaplasia in Wistar rats by X-ray irradiation. Gastroenterology 1978; 75:796.
  6. Correa P, Cuello C, Duque E. Carcinoma and intestinal metaplasia of the stomach in Colombian migrants. J Natl Cancer Inst 1970; 44:297.
  7. Sasajima K, Kawachi T, Matsukura N, et al. Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N-propyl-N'-nitro-N-nitrosoguanidine. J Cancer Res Clin Oncol 1979; 94:201.
  8. Shimoyama T, Fukuda S, Tanaka M, et al. Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori. Virchows Arch 2000; 436:585.
  9. You WC, Blot WJ, Li JY, et al. Precancerous gastric lesions in a population at high risk of stomach cancer. Cancer Res 1993; 53:1317.
  10. Rugge M, Farinati F, Baffa R, et al. Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia. Gastroenterology 1994; 107:1288.
  11. Song H, Ekheden IG, Zheng Z, et al. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population. BMJ 2015; 351:h3867.
  12. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Schistosomes, Liver Flukes and Helicobacter pylori. Vol 61 of IARC monographs on the evaluation of carcinogenic risks to humans. International Agency for Research on Cancer, Lyon, 1994.
  13. Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer 2007; 10:75.
  14. World Health Organization. Diet, nutrition, and the prevention of chronic diseases. WHO technical report series 916. Geneva; World Health Organization; 2003.
  15. Joossens JV, Hill MJ, Elliott P, et al. Dietary salt, nitrate and stomach cancer mortality in 24 countries. European Cancer Prevention (ECP) and the INTERSALT Cooperative Research Group. Int J Epidemiol 1996; 25:494.
  16. Kono S, Hirohata T. Nutrition and stomach cancer. Cancer Causes Control 1996; 7:41.
  17. Shikata K, Kiyohara Y, Kubo M, et al. A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study. Int J Cancer 2006; 119:196.
  18. Peleteiro B, Lopes C, Figueiredo C, Lunet N. Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type. Br J Cancer 2011; 104:198.
  19. Kronsteiner-Gicevic S, Thompson AS, Gaggl M, et al. Adding salt to food at table as an indicator of gastric cancer risk among adults: a prospective study. Gastric Cancer 2024; 27:714.
  20. Phukan RK, Narain K, Zomawia E, et al. Dietary habits and stomach cancer in Mizoram, India. J Gastroenterol 2006; 41:418.
  21. Ren JS, Kamangar F, Forman D, Islami F. Pickled food and risk of gastric cancer--a systematic review and meta-analysis of English and Chinese literature. Cancer Epidemiol Biomarkers Prev 2012; 21:905.
  22. Raei N, Behrouz B, Zahri S, Latifi-Navid S. Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer. Asian Pac J Cancer Prev 2016; 17:917.
  23. World Cancer Research Fund/American Institute for Cancer Research (2007). Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. World Cancer Research Fund/American Institute for Cancer Research: Washington DC.
  24. Collatuzzo G, Pelucchi C, Negri E, et al. Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project. Int J Cancer 2021; 149:1228.
  25. Tatematsu M, Takahashi M, Fukushima S, et al. Effects in rats of sodium chloride on experimental gastric cancers induced by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. J Natl Cancer Inst 1975; 55:101.
  26. Takahashi M, Kokubo T, Furukawa F, et al. Effects of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. Gan 1984; 75:494.
  27. Hanawa K, Yamada S, Suzuki H, et al. Effects of sodium chloride on gastric cancer induction by N-methyl-N-Nitro-N-nitrogoguanidine (MNNG) in rats. Proceedings of the Thirty-ninth Annual Meeting of the Japanese Cancer Association, Tokyo: Japanese Cancer Association, 1980. p.49.
  28. Park B, Shin A, Park SK, et al. Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer. Cancer Causes Control 2011; 22:1497.
  29. Tricker AR. N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids. Eur J Cancer Prev 1997; 6:226.
  30. You WC, Zhang L, Yang CS, et al. Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions. Cancer Epidemiol Biomarkers Prev 1996; 5:47.
  31. Jakszyn P, Bingham S, Pera G, et al. Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study. Carcinogenesis 2006; 27:1497.
  32. González CA, Jakszyn P, Pera G, et al. Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006; 98:345.
  33. Zhu H, Yang X, Zhang C, et al. Red and processed meat intake is associated with higher gastric cancer risk: a meta-analysis of epidemiological observational studies. PLoS One 2013; 8:e70955.
  34. Larsson SC, Orsini N, Wolk A. Processed meat consumption and stomach cancer risk: a meta-analysis. J Natl Cancer Inst 2006; 98:1078.
  35. Bouvard V, Loomis D, Guyton KZ, et al. Carcinogenicity of consumption of red and processed meat. Lancet Oncol 2015; 16:1599.
  36. Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006; 131:1271.
  37. Yang P, Zhou Y, Chen B, et al. Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur J Cancer 2009; 45:2867.
  38. Turati F, Tramacere I, La Vecchia C, Negri E. A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Ann Oncol 2013; 24:609.
  39. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med 2016; 375:794.
  40. Ladeiras-Lopes R, Pereira AK, Nogueira A, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control 2008; 19:689.
  41. González CA, Pera G, Agudo A, et al. Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer 2003; 107:629.
  42. Brenner H, Arndt V, Bode G, et al. Risk of gastric cancer among smokers infected with Helicobacter pylori. Int J Cancer 2002; 98:446.
  43. Simán JH, Forsgren A, Berglund G, Florén CH. Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals. Scand J Gastroenterol 2001; 36:208.
  44. Zaridze D, Borisova E, Maximovitch D, Chkhikvadze V. Alcohol consumption, smoking and risk of gastric cancer: case-control study from Moscow, Russia. Cancer Causes Control 2000; 11:363.
  45. Ferro A, Morais S, Pelucchi C, et al. Smoking and Helicobacter pylori infection: an individual participant pooled analysis (Stomach Cancer Pooling- StoP Project). Eur J Cancer Prev 2019; 28:390.
  46. Raj A, Mayberry JF, Podas T. Occupation and gastric cancer. Postgrad Med J 2003; 79:252.
  47. Straif K, Chambless L, Weiland SK, et al. Occupational risk factors for mortality from stomach and lung cancer among rubber workers: an analysis using internal controls and refined exposure assessment. Int J Epidemiol 1999; 28:1037.
  48. Jenkins WD, Christian WJ, Mueller G, Robbins KT. Population cancer risks associated with coal mining: a systematic review. PLoS One 2013; 8:e71312.
  49. Pang D, Burges DC, Sorahan T. Mortality study of nickel platers with special reference to cancers of the stomach and lung, 1945-93. Occup Environ Med 1996; 53:714.
  50. Tsugane S, Tei Y, Takahashi T, et al. Salty food intake and risk of Helicobacter pylori infection. Jpn J Cancer Res 1994; 85:474.
  51. Fox JG, Dangler CA, Taylor NS, et al. High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res 1999; 59:4823.
  52. Lee SA, Kang D, Shim KN, et al. Effect of diet and Helicobacter pylori infection to the risk of early gastric cancer. J Epidemiol 2003; 13:162.
  53. Machida-Montani A, Sasazuki S, Inoue M, et al. Association of Helicobacter pylori infection and environmental factors in non-cardia gastric cancer in Japan. Gastric Cancer 2004; 7:46.
  54. Shin WS, Kang MW, Kang JH, et al. Epstein-Barr virus-associated gastric adenocarcinomas among Koreans. Am J Clin Pathol 1996; 105:174.
  55. Takada K. Epstein-Barr virus and gastric carcinoma. Mol Pathol 2000; 53:255.
  56. Boysen T, Mohammadi M, Melbye M, et al. EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma. Br J Cancer 2009; 101:530.
  57. Chang MS, Uozaki H, Chong JM, et al. CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res 2006; 12:2995.
  58. Sakuma K, Chong JM, Sudo M, et al. High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 2004; 112:273.
  59. Kusano M, Toyota M, Suzuki H, et al. Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus. Cancer 2006; 106:1467.
  60. Kaneda A, Kaminishi M, Yanagihara K, et al. Identification of silencing of nine genes in human gastric cancers. Cancer Res 2002; 62:6645.
  61. Etoh T, Kanai Y, Ushijima S, et al. Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol 2004; 164:689.
  62. Fukayama M. Epstein-Barr virus and gastric carcinoma. Pathol Int 2010; 60:337.
  63. Zhao J, Jin H, Cheung KF, et al. Zinc finger E-box binding factor 1 plays a central role in regulating Epstein-Barr virus (EBV) latent-lytic switch and acts as a therapeutic target in EBV-associated gastric cancer. Cancer 2012; 118:924.
  64. Murphy G, Pfeiffer R, Camargo MC, Rabkin CS. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology 2009; 137:824.
  65. van Beek J, zur Hausen A, Klein Kranenbarg E, et al. EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol 2004; 22:664.
  66. Wu MS, Shun CT, Wu CC, et al. Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations. Gastroenterology 2000; 118:1031.
  67. Lee JH, Kim SH, Han SH, et al. Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol 2009; 24:354.
  68. Fukayama M, Chong JM, Uozaki H. Pathology and molecular pathology of Epstein-Barr virus-associated gastric carcinoma. Curr Top Microbiol Immunol 2001; 258:91.
  69. Barstad B, Sørensen TI, Tjønneland A, et al. Intake of wine, beer and spirits and risk of gastric cancer. Eur J Cancer Prev 2005; 14:239.
  70. Tramacere I, Negri E, Pelucchi C, et al. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol 2012; 23:28.
  71. Wang S, Freedman ND, Loftfield E, et al. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric noncardia adenocarcinoma: A 16-year prospective analysis from the NIH-AARP diet and health cohort. Int J Cancer 2018; 143:2749.
  72. Wang PL, Xiao FT, Gong BC, Liu FN. Alcohol drinking and gastric cancer risk: a meta-analysis of observational studies. Oncotarget 2017; 8:99013.
  73. Fang X, Wei J, He X, et al. Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies. Eur J Cancer 2015; 51:2820.
  74. HAENSZEL W. Variation in incidence of and mortality from stomach cancer, with particular reference to the United States. J Natl Cancer Inst 1958; 21:213.
  75. WYNDER EL, KMET J, DUNGAL N, SEGI M. AN EPIDEMIOLOGICAL INVESTIGATION OF GASTRIC CANCER. Cancer 1963; 16:1461.
  76. Berndt H, Wildner GP, Klein K. Regional and social differences in cancer incidence of the digestive tract in the German Democratic Republic. Neoplasma 1968; 15:501.
  77. Barker DJ, Coggon D, Osmond C, Wickham C. Poor housing in childhood and high rates of stomach cancer in England and Wales. Br J Cancer 1990; 61:575.
  78. Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer 1990; 62:440.
  79. Viste A, Bjørnestad E, Opheim P, et al. Risk of carcinoma following gastric operations for benign disease. A historical cohort study of 3470 patients. Lancet 1986; 2:502.
  80. Sitarz R, Maciejewski R, Polkowski WP, Offerhaus GJ. Gastroenterostoma after Billroth antrectomy as a premalignant condition. World J Gastroenterol 2012; 18:3201.
  81. Tersmette AC, Offerhaus GJ, Tersmette KW, et al. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions. Cancer Res 1990; 50:6486.
  82. Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol 1996; 23:281.
  83. Takeno S, Hashimoto T, Maki K, et al. Gastric cancer arising from the remnant stomach after distal gastrectomy: a review. World J Gastroenterol 2014; 20:13734.
  84. Ahn HS, Kim JW, Yoo MW, et al. Clinicopathological features and surgical outcomes of patients with remnant gastric cancer after a distal gastrectomy. Ann Surg Oncol 2008; 15:1632.
  85. Komatsu S, Ichikawa D, Okamoto K, et al. Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy. World J Gastroenterol 2012; 18:2832.
  86. Stalnikowicz R, Benbassat J. Risk of gastric cancer after gastric surgery for benign disorders. Arch Intern Med 1990; 150:2022.
  87. Caygill CP, Hill MJ, Hall CN, et al. Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer. Gut 1987; 28:924.
  88. Toftgaard C. Gastric cancer after peptic ulcer surgery. A historic prospective cohort investigation. Ann Surg 1989; 210:159.
  89. Safatle-Ribeiro AV, Ribeiro U Jr, Reynolds JC. Gastric stump cancer: what is the risk? Dig Dis 1998; 16:159.
  90. Henderson TO, Oeffinger KC, Whitton J, et al. Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med 2012; 156:757.
  91. Morton LM, Dores GM, Curtis RE, et al. Stomach cancer risk after treatment for hodgkin lymphoma. J Clin Oncol 2013; 31:3369.
  92. Lunet N, Valbuena C, Vieira AL, et al. Fruit and vegetable consumption and gastric cancer by location and histological type: case-control and meta-analysis. Eur J Cancer Prev 2007; 16:312.
  93. Liu C, Russell RM. Nutrition and gastric cancer risk: an update. Nutr Rev 2008; 66:237.
  94. Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr 2003; 78:559S.
  95. Larsson SC, Bergkvist L, Wolk A. Fruit and vegetable consumption and incidence of gastric cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 2006; 15:1998.
  96. Ferro A, Costa AR, Morais S, et al. Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project. Int J Cancer 2020; 147:3090.
  97. Epplein M, Nomura AM, Hankin JH, et al. Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii. Cancer Causes Control 2008; 19:869.
  98. La Vecchia C, Negri E, Decarli A, et al. A case-control study of diet and gastric cancer in northern Italy. Int J Cancer 1987; 40:484.
  99. Wang Q, Chen Y, Wang X, et al. Consumption of fruit, but not vegetables, may reduce risk of gastric cancer: results from a meta-analysis of cohort studies. Eur J Cancer 2014; 50:1498.
  100. Buiatti E, Palli D, Decarli A, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer 1989; 44:611.
  101. Zhang Z, Xu G, Ma M, et al. Dietary fiber intake reduces risk for gastric cancer: a meta-analysis. Gastroenterology 2013; 145:113.
  102. M A M, Pera G, Agudo A, et al. Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study. Int J Cancer 2007; 121:1618.
  103. Wu CY, Wu MS, Kuo KN, et al. Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori-infected patients. J Clin Oncol 2010; 28:2952.
  104. Epplein M, Nomura AM, Wilkens LR, et al. Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study. Am J Epidemiol 2009; 170:507.
  105. Freedman ND, Chow WH, Gao YT, et al. Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women. Gut 2007; 56:1671.
  106. Duell EJ, Travier N, Lujan-Barroso L, et al. Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol 2010; 172:1384.
  107. Wang Z, Butler LM, Wu AH, et al. Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study. Int J Cancer 2016; 138:2837.
  108. Oliveira C, Pinheiro H, Figueiredo J, et al. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol 2015; 16:e60.
  109. Blair VR, McLeod M, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol 2020; 21:e386.
  110. Worthley DL, Phillips KD, Wayte N, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut 2012; 61:774.
  111. Li J, Woods SL, Healey S, et al. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am J Hum Genet 2016; 98:830.
  112. Yanaru-Fujisawa R, Nakamura S, Moriyama T, et al. Familial fundic gland polyposis with gastric cancer. Gut 2012; 61:1103.
  113. Repak R, Kohoutova D, Podhola M, et al. The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature. Gastrointest Endosc 2016; 84:718.
  114. Caldas C, Carneiro F, Lynch HT, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet 1999; 36:873.
  115. Corso G, Roncalli F, Marrelli D, et al. History, pathogenesis, and management of familial gastric cancer: original study of John XXIII's family. Biomed Res Int 2013; 2013:385132.
  116. Usui Y, Taniyama Y, Endo M, et al. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. N Engl J Med 2023; 388:1181.
  117. Dominici P, Bellentani S, Di Biase AR, et al. Familial clustering of Helicobacter pylori infection: population based study. BMJ 1999; 319:537.
  118. Brenner H, Arndt V, Stürmer T, et al. Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma. Cancer 2000; 88:274.
  119. Yatsuya H, Toyoshima H, Tamakoshi A, et al. Individual and joint impact of family history and Helicobacter pylori infection on the risk of stomach cancer: a nested case-control study. Br J Cancer 2004; 91:929.
  120. Bonney GE, Elston RC, Correa P, et al. Genetic etiology of gastric carcinoma: I. Chronic atrophic gastritis. Genet Epidemiol 1986; 3:213.
  121. Choi IJ, Kim CG, Lee JY, et al. Family History of Gastric Cancer and Helicobacter pylori Treatment. N Engl J Med 2020; 382:427.
  122. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000; 404:398.
  123. Figueiredo C, Machado JC, Pharoah P, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 2002; 94:1680.
  124. Thye T, Burchard GD, Nilius M, et al. Genomewide linkage analysis identifies polymorphism in the human interferon-gamma receptor affecting Helicobacter pylori infection. Am J Hum Genet 2003; 72:448.
  125. Zintzaras E. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis. J Hum Genet 2006; 51:618.
  126. Langman MJS. Genetic influences upon gastric cancer frequency. In: Gastric carcinogenesis, Reed PI, Hill MJ (Eds), Excerpta Medica, Amsterdam 1988. p.81.
  127. Hoskins LC, Loux HA, Britten A, Zamcheck N. Distribution of ABO blood groups in patients with pernicious anemia, gastric carcinoma and gastric carcinoma associated with pernicious anemia. N Engl J Med 1965; 273:633.
  128. Arid I, Bentall HH, Robert JAF. A relationship between cancer of the stomach and the ABO blood groups. Br Med J 1953; i:799.
  129. Edgren G, Hjalgrim H, Rostgaard K, et al. Risk of gastric cancer and peptic ulcers in relation to ABO blood type: a cohort study. Am J Epidemiol 2010; 172:1280.
  130. Menetrier P. Des polyadenomas gastriques et de leurs rapports avec le cancer de l'estomac. Arch Physiol Norm Pathol 1888; 1:322.
  131. Kinlen LJ, Webster AD, Bird AG, et al. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet 1985; 1:263.
  132. IHRE BJ, BARR H, HAVERMARK G. ULCER-CANCER OF THE STOMACH. A FOLLOW-UP STUDY OF 473 CASES OF GASTRIC ULCER. Gastroenterologia 1964; 102:78.
  133. Hirohata T. Mortality from gastric cancer and other causes after medical or surgical treatment for gastric ulcer. J Natl Cancer Inst 1968; 41:895.
  134. Rollag A, Jacobsen CD. Gastric ulcer and risk of cancer. A five-year follow-up study. Acta Med Scand 1984; 216:105.
  135. Lee S, Iida M, Yao T, et al. Risk of gastric cancer in patients with non-surgically treated peptic ulcer. Scand J Gastroenterol 1990; 25:1223.
  136. Hansson LE, Nyrén O, Hsing AW, et al. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N Engl J Med 1996; 335:242.
  137. Take S, Mizuno M, Ishiki K, et al. The effect of eradicating helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol 2005; 100:1037.
  138. Take S, Mizuno M, Ishiki K, et al. Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases. J Gastroenterol 2007; 42 Suppl 17:21.
  139. Brinton LA, Gridley G, Hrubec Z, et al. Cancer risk following pernicious anaemia. Br J Cancer 1989; 59:810.
  140. Hsing AW, Hansson LE, McLaughlin JK, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer 1993; 71:745.
  141. Landgren AM, Landgren O, Gridley G, et al. Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans. Cancer 2011; 117:1163.
  142. Vannella L, Lahner E, Osborn J, et al. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther 2013; 37:375.
  143. Song M, Camargo MC, Katki HA, et al. Association of Antiparietal Cell and Anti-Intrinsic Factor Antibodies With Risk of Gastric Cancer. JAMA Oncol 2022; 8:268.
  144. Harvey RF, Bradshaw MJ, Davidson CM, et al. Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia. Lancet 1985; 1:951.
  145. La Vecchia C, Negri E, D'Avanzo B, Franceschi S. Histamine-2-receptor antagonists and gastric cancer risk. Lancet 1990; 336:355.
  146. Colin-Jones DG, Langman MJ, Lawson DH, et al. Postmarketing surveillance of the safety of cimetidine: 10 year mortality report. Gut 1992; 33:1280.
  147. Møller H, Nissen A, Mosbech J. Use of cimetidine and other peptic ulcer drugs in Denmark 1977-1990 with analysis of the risk of gastric cancer among cimetidine users. Gut 1992; 33:1166.
  148. Klinkenberg-Knol EC, Festen HP, Jansen JB, et al. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med 1994; 121:161.
  149. Liu P, McMenamin ÚC, Johnston BT, et al. Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies. Br J Cancer 2020; 123:307.
  150. Guidelines from the ASGE available online at http://www.asge.org/assets/0/71542/71544/db54732efefe4808b65e317ea6e4e5ee.pdf (Accessed on January 29, 2013).
  151. Schorah CJ, Sobala GM, Sanderson M, et al. Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. Am J Clin Nutr 1991; 53:287S.
  152. Parsonnet J. Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am 1993; 22:89.
Topic 2617 Version 69.0

References

1 : The gastric precancerous process

2 : A human model of gastric carcinogenesis.

3 : Acid suppression and gastric atrophy: sifting fact from fiction.

4 : Bile reflux and intestinal metaplasia in gastric mucosa.

5 : Experimentally induced intestinal metaplasia in Wistar rats by X-ray irradiation.

6 : Carcinoma and intestinal metaplasia of the stomach in Colombian migrants.

7 : Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N-propyl-N'-nitro-N-nitrosoguanidine.

8 : Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori.

9 : Precancerous gastric lesions in a population at high risk of stomach cancer.

10 : Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia.

11 : Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population.

12 : Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population.

13 : Diet and the risk of gastric cancer: review of epidemiological evidence.

14 : Diet and the risk of gastric cancer: review of epidemiological evidence.

15 : Dietary salt, nitrate and stomach cancer mortality in 24 countries. European Cancer Prevention (ECP) and the INTERSALT Cooperative Research Group.

16 : Nutrition and stomach cancer.

17 : A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study.

18 : Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type.

19 : Adding salt to food at table as an indicator of gastric cancer risk among adults: a prospective study.

20 : Dietary habits and stomach cancer in Mizoram, India.

21 : Pickled food and risk of gastric cancer--a systematic review and meta-analysis of English and Chinese literature.

22 : Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer.

23 : Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer.

24 : Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project.

25 : Effects in rats of sodium chloride on experimental gastric cancers induced by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide.

26 : Effects of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

27 : Effects of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

28 : Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer.

29 : N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids.

30 : Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

31 : Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

32 : Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC).

33 : Red and processed meat intake is associated with higher gastric cancer risk: a meta-analysis of epidemiological observational studies.

34 : Processed meat consumption and stomach cancer risk: a meta-analysis.

35 : Carcinogenicity of consumption of red and processed meat.

36 : Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis.

37 : Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies.

38 : A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma.

39 : Body Fatness and Cancer--Viewpoint of the IARC Working Group.

40 : Smoking and gastric cancer: systematic review and meta-analysis of cohort studies.

41 : Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).

42 : Risk of gastric cancer among smokers infected with Helicobacter pylori.

43 : Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals.

44 : Alcohol consumption, smoking and risk of gastric cancer: case-control study from Moscow, Russia.

45 : Smoking and Helicobacter pylori infection: an individual participant pooled analysis (Stomach Cancer Pooling- StoP Project).

46 : Occupation and gastric cancer.

47 : Occupational risk factors for mortality from stomach and lung cancer among rubber workers: an analysis using internal controls and refined exposure assessment.

48 : Population cancer risks associated with coal mining: a systematic review.

49 : Mortality study of nickel platers with special reference to cancers of the stomach and lung, 1945-93.

50 : Salty food intake and risk of Helicobacter pylori infection.

51 : High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice.

52 : Effect of diet and Helicobacter pylori infection to the risk of early gastric cancer.

53 : Association of Helicobacter pylori infection and environmental factors in non-cardia gastric cancer in Japan.

54 : Epstein-Barr virus-associated gastric adenocarcinomas among Koreans.

55 : Epstein-Barr virus and gastric carcinoma.

56 : EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma.

57 : CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus.

58 : High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma.

59 : Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus.

60 : Identification of silencing of nine genes in human gastric cancers.

61 : Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers.

62 : Epstein-Barr virus and gastric carcinoma.

63 : Zinc finger E-box binding factor 1 plays a central role in regulating Epstein-Barr virus (EBV) latent-lytic switch and acts as a therapeutic target in EBV-associated gastric cancer.

64 : Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location.

65 : EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement.

66 : Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations.

67 : Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis.

68 : Pathology and molecular pathology of Epstein-Barr virus-associated gastric carcinoma.

69 : Intake of wine, beer and spirits and risk of gastric cancer.

70 : A meta-analysis on alcohol drinking and gastric cancer risk.

71 : Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric noncardia adenocarcinoma: A 16-year prospective analysis from the NIH-AARP diet and health cohort.

72 : Alcohol drinking and gastric cancer risk: a meta-analysis of observational studies.

73 : Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies.

74 : Variation in incidence of and mortality from stomach cancer, with particular reference to the United States.

75 : AN EPIDEMIOLOGICAL INVESTIGATION OF GASTRIC CANCER.

76 : Regional and social differences in cancer incidence of the digestive tract in the German Democratic Republic.

77 : Poor housing in childhood and high rates of stomach cancer in England and Wales.

78 : Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites.

79 : Risk of carcinoma following gastric operations for benign disease. A historical cohort study of 3470 patients.

80 : Gastroenterostoma after Billroth antrectomy as a premalignant condition.

81 : Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions.

82 : Epidemiology of gastric cancer.

83 : Gastric cancer arising from the remnant stomach after distal gastrectomy: a review.

84 : Clinicopathological features and surgical outcomes of patients with remnant gastric cancer after a distal gastrectomy.

85 : Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy.

86 : Risk of gastric cancer after gastric surgery for benign disorders.

87 : Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer.

88 : Gastric cancer after peptic ulcer surgery. A historic prospective cohort investigation.

89 : Gastric stump cancer: what is the risk?

90 : Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study.

91 : Stomach cancer risk after treatment for hodgkin lymphoma.

92 : Fruit and vegetable consumption and gastric cancer by location and histological type: case-control and meta-analysis.

93 : Nutrition and gastric cancer risk: an update.

94 : Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk.

95 : Fruit and vegetable consumption and incidence of gastric cancer: a prospective study.

96 : Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project.

97 : Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii.

98 : A case-control study of diet and gastric cancer in northern Italy.

99 : Consumption of fruit, but not vegetables, may reduce risk of gastric cancer: results from a meta-analysis of cohort studies.

100 : A case-control study of gastric cancer and diet in Italy.

101 : Dietary fiber intake reduces risk for gastric cancer: a meta-analysis.

102 : Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study.

103 : Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori-infected patients.

104 : Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study.

105 : Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women.

106 : Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition.

107 : Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study.

108 : Familial gastric cancer: genetic susceptibility, pathology, and implications for management.

109 : Hereditary diffuse gastric cancer: updated clinical practice guidelines.

110 : Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome.

111 : Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

112 : Familial fundic gland polyposis with gastric cancer.

113 : The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature.

114 : Familial gastric cancer: overview and guidelines for management.

115 : History, pathogenesis, and management of familial gastric cancer: original study of John XXIII's family.

116 : Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer.

117 : Familial clustering of Helicobacter pylori infection: population based study.

118 : Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma.

119 : Individual and joint impact of family history and Helicobacter pylori infection on the risk of stomach cancer: a nested case-control study.

120 : Genetic etiology of gastric carcinoma: I. Chronic atrophic gastritis.

121 : Family History of Gastric Cancer and Helicobacter pylori Treatment.

122 : Interleukin-1 polymorphisms associated with increased risk of gastric cancer.

123 : Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma.

124 : Genomewide linkage analysis identifies polymorphism in the human interferon-gamma receptor affecting Helicobacter pylori infection.

125 : Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis.

126 : Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis.

127 : Distribution of ABO blood groups in patients with pernicious anemia, gastric carcinoma and gastric carcinoma associated with pernicious anemia.

128 : A relationship between cancer of the stomach and the ABO blood groups

129 : Risk of gastric cancer and peptic ulcers in relation to ABO blood type: a cohort study.

130 : Des polyadenomas gastriques et de leurs rapports avec le cancer de l'estomac

131 : Prospective study of cancer in patients with hypogammaglobulinaemia.

132 : ULCER-CANCER OF THE STOMACH. A FOLLOW-UP STUDY OF 473 CASES OF GASTRIC ULCER.

133 : Mortality from gastric cancer and other causes after medical or surgical treatment for gastric ulcer.

134 : Gastric ulcer and risk of cancer. A five-year follow-up study.

135 : Risk of gastric cancer in patients with non-surgically treated peptic ulcer.

136 : The risk of stomach cancer in patients with gastric or duodenal ulcer disease.

137 : The effect of eradicating helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease.

138 : Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases.

139 : Cancer risk following pernicious anaemia.

140 : Pernicious anemia and subsequent cancer. A population-based cohort study.

141 : Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans.

142 : Systematic review: gastric cancer incidence in pernicious anaemia.

143 : Association of Antiparietal Cell and Anti-Intrinsic Factor Antibodies With Risk of Gastric Cancer.

144 : Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia.

145 : Histamine-2-receptor antagonists and gastric cancer risk.

146 : Postmarketing surveillance of the safety of cimetidine: 10 year mortality report.

147 : Use of cimetidine and other peptic ulcer drugs in Denmark 1977-1990 with analysis of the risk of gastric cancer among cimetidine users.

148 : Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety.

149 : Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.

150 : Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.

151 : Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis.

152 : Helicobacter pylori and gastric cancer.