Risk Of Distal Gastric Cancer Research Articles

Diabetic biomarkers and the risk of proximal or distal gastric cancer.

The role of diabetes mellitus as a risk factor for gastric cancer has been controversial. We studied the association between diabetic biomarkers and the risk of gastric cancer and whether these associations depend on cancer location. In this retrospective cohort study with subjects with negative initial esophagogastroduodenoscopy findings (n = 23 218) during a routine health checkup, we measured fasting glucose and insulin levels, calculated the homeostatic model assessment insulin resistance (HOMA-IR) values, and analyzed the risk of gastric cancer in relation to diabetic biomarker tertiles and the presence of diabetes mellitus. The incidence rate of gastric cancer was 9.7 per 10 000 person-years during the mean 6.8-year follow up. Patients with diabetes, higher fasting glucose levels, or higher HOMA-IR levels were older; men, current smokers, and heavy alcohol consumers represented larger proportions of these groups. They also had high body mass index and hemoglobin A1c more often. In the multivariate-adjusted Cox regression analyses, the incidence of gastric cancer was not significantly associated with diabetes mellitus or higher diabetic biomarker levels. Compared with normal glucose levels, lower glucose levels were significantly associated with an increased risk of distal gastric cancer. The hazard ratio for fasting glucose level tertile 1 was 2.39 (95% confidence interval, 1.48-3.85) (reference, tertile 2). Lower glucose levels were not associated with a risk of proximal gastric cancer, compared with a normal glucose level. Our findings suggest that fasting glucose levels have a different effect on distal and proximal gastric cancers.

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies

Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men.

Intake of Specific Nonfermented Soy Foods May Be Inversely Associated with Risk of Distal Gastric Cancer in a Chinese Population

Because the association between soy consumption and gastric cancer is inconsistent, we evaluated the putative preventive effect of soy food on gastric cancer risk in the Shanghai Women's and Men's Health Studies, comprising a total of 128,687 participants. Intake of nonfermented soy foods was estimated using 2 validated food-frequency questionnaires. HRs were calculated with 95% CIs for intake amounts of total nonfermented soy food intake, soy protein, and isoflavones as well as individual soy food groups using Cox proportional hazards regression. A total of 493 distal gastric cancer cases were identified by 2010. Although all risk estimates for summary measures of soy food intake above the lowest quartile (quartile 1) were suggestive of a protective effect, no statistically significant associations with risk of distal gastric cancer were found. Among the separate soy food groups, significant reductions in risk of distal gastric cancer by increasing intake of tofu were found in men in quartile 2 (HR: 0.59; 95% CI: 0.40, 0.86), quartile 3 (HR: 0.62; 95% CI: 0.44, 0.88), and quartile 4 (HR: 0.64; 95% CI: 0.42, 0.99), resulting in a significant trend (P-trend = 0.02). Dry bean intake was also inversely associated with decreased risk of gastric cancer, but in postmenopausal women only [quartile 2 (HR: 0.54; 95% CI: 0.30, 0.96); quartile 3 (HR: 0.90; 95% CI: 0.64, 1.27); and quartile 4 (HR: 0.63; 95% CI: 0.43, 0.91)], resulting in a significant trend (P-trend = 0.03). Overall, our study found no statistically significant association between nonfermented soy food intake and distal gastric cancer risk, though the data supported the hypothesis that tofu may protect against distal gastric cancer in men and dry bean consumption may decrease the risk of gastric cancer in postmenopausal women.

Circulating cytokines and gastric cancer risk

Chronic inflammation has been hypothesized to play a significant role in the aetiology of cancer, including gastric cancer. In the present study, we sought to examine pre-diagnostic systemic cytokine levels in plasma, which can be seen as markers of aggregate inflammation, and risk of distal gastric cancer in a case-control study nested within the prospective Shanghai Men's Health Study. Circulating levels of eight inflammation-related cytokines were measured in the plasma collected at baseline for 180 incident cases of distal gastric cancer and 358 matched controls. Helicobacter pylori sero-positivity was assessed using multiplex serology. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CI). Individuals with IL-8 levels above the lowest quartile were at twofold increased odds of gastric cancer [OR 1.91 (95 % CI 1.05-3.46), OR 2.10 (95 % CI 1.19-3.74), and OR 2.30 (95 % CI 1.26-4.19), for the second through fourth quartiles, respectively]. While there were suggestions of an increase in risk with increased level of many of the other cytokines measured (IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ), no significant associations were found at the p < 0.05 level. Infection with CagA-positive H. pylori did not modify these associations. In a population with high gastric cancer incidence and high H. pylori prevalence, increased circulating levels of IL-8 may indicate increased risk of gastric cancer. These findings add to our understanding of the disease and further efforts to uncover biomarkers of disease risk.

Fruit and Vegetable Consumption and Risk of Distal Gastric Cancer in the Shanghai Women's and Men's Health Studies

Results from case-control and cohort studies of the association between fruit and vegetable consumption and gastric cancer risk have been inconsistent. Cases for the current study consisted of incident distal gastric cancers identified between 1996 and 2007 among members of the Shanghai Women's Health Study (n = 206) and the Shanghai Men's Health Study (n = 132). Intakes of fruits, vegetables, and select micronutrients were assessed on the basis of validated food frequency questionnaires. Multivariate-adjusted hazards ratios and 95% confidence intervals were calculated by Cox proportional hazards regression. For women, no associations were found between gastric cancer risk and the highest intake of fruits (hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.68, 1.54; P(trend) = 0.87) or vegetables (HR = 0.89, 95% CI: 0.60, 1.31; P(trend) = 0.32). For men, increased fruit intake was associated with decreased risk of distal gastric cancer (for the highest quartile of intake, HR = 0.50, 95% CI: 0.29, 0.84; P(trend) = 0.004), but no association was seen with increased intake of vegetables (HR = 1.00, 95% CI: 0.59, 1.68; P(trend) = 0.87). The inverse association with fruit intake for men was more evident among ever smokers (P(trend) = 0.001) than never smokers (P(trend) = 0.67). No associations between dietary intakes of select antioxidant micronutrients were seen for men or women. Fruit intake is inversely associated with distal gastric cancer risk among men in Shanghai, China.

Nonsteroidal Antiinflammatory Drugs and Risk of Gastric Adenocarcinoma: The Multiethnic Cohort Study

In many epidemiologic studies, investigators have reported an inverse relation between nonsteroidal antiinflammatory drugs (NSAIDs) and colon cancer, but fewer researchers have examined the relation with gastric cancer. Cases for this study consisted of incident gastric adenocarcinomas (n = 643) identified between 1993 and 2004 among members of the Multiethnic Cohort (Hawaii and Los Angeles, California). Aspirin and nonaspirin NSAID use was assessed on the basis of a self-administered questionnaire. Multivariate-adjusted hazards ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. Compared with no regular use, regular use of aspirin was associated with a decreased risk of distal gastric cancer (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.61, 0.89; P(trend) = 0.009), but use of nonaspirin NSAIDs was not (HR = 1.00, 95% CI: 0.81, 1.24; P(trend) = 0.99). The inverse association with regular aspirin use was observed only for intestinal-type distal gastric adenocarcinoma (HR = 0.66, 95% CI: 0.47, 0.95; P(trend) = 0.01), as opposed to diffuse-type distal gastric adenocarcinoma (HR = 0.92, 95% CI: 0.53, 1.60; P(trend) = 0.45). In this study, the authors found aspirin use to be inversely associated with distal gastric adenocarcinoma, particularly of the intestinal type.

Green tea consumption and gastric cancer in Japanese: a pooled analysis of six cohort studies

Background:Previous experimental studies have suggested many possible anti-cancer mechanisms for green tea, but epidemiological evidence for the effect of green tea consumption on gastric cancer risk is conflicting.Objective:To examine the...

The Association Between the Survivin C-31G Polymorphism and Gastric Cancer Risk in a Chinese Population

The C-31G polymorphism in the survivin promoter could de-repress the cell-cycle-dependent transcription of the human survivin gene, resulting in overexpression of survivin. This survivin mutation has only been studied on cervical carcinoma. However, no study has ever been conducted to evaluate the effect of the polymorphism on other cancers, including gastric cancer. In this hospital-based, case-control study, we investigated the association between the survivin C-31G polymorphism and risk of gastric cancer in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocols. No statistically significant association was observed between gastric cancer risk and the variant genotype (GG + GC). However, the variant genotype (GG + GC) was either associated with risk of distal gastric cancer (odds ratios=0.50, 95% confidence interval=0.30-0.83) or with risk of well-differentiated tumor (odds ratios=0.46, 95% confidence interval=0.22-0.97). Our results demonstrate that the survivin C-31G polymorphism may be involved in distal gastric carcinogenesis and tumor differentiation in a Chinese population.

Risk for Gastric Cancer After Cholecystectomy

It is becoming increasingly evident that chronic inflammation may predispose cancer development. In the stomach, inflammation caused by Helicobacter pylori infection is linked to gastric cancer. Cholecystectomy is regularly followed by duodenogastric bile reflux and reactive gastritis. To test whether a noninfectious long-standing inflammation impels gastric carcinogenesis as well, we assessed the risk of gastric cancer in a large, population-based cohort of cholecystectomized patients. We identified 251,672 individuals, in the Swedish National Inpatient Register, who had undergone cholecystectomy between 1970 and 1997. All incident cases of gastric cancer were identified through linkage to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for comparisons with cancer rates of the general population in Sweden. We found an 11% greater overall risk of distal gastric cancer (SIR=1.11, 95% CI 1.04-1.19). The risk increase was only observed among men (SIR=1.21, 95% CI 1.10-1.32), whereas no excess risk was evident for women. For men, the risk was elevated for up to 10 yr after surgery, but this elevation disappeared with longer follow-up time. There was no clear association between cholecystectomy and cardia cancer (SIR=0.95, 95% CI 0.76-1.16). Inconsistency over gender strata, implausibly short induction and latency time, and disappearance of the effect over time makes a causal relationship between cholecystectomy and distal gastric cancer less likely. The findings set aside concerns of harmful long-term consequences of cholecystectomy.

Association of Helicobacter pylori‐related Distal Gastric Cancer with the HLA Class II Gene DQB1*0602 and cagA+ Strains in a Southern European Population

Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population. In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies. Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the (*)0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1(*)0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94). Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.

Role of the polymorphic IL‐1B, IL‐1RN and TNF‐A genes in distal gastric cancer in Mexico

Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL-1B-31, IL-1RN and TNF-A-308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon. The subjects were divided into 2 groups. Sixty-three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22-84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18-92, F:M = 1.17). The IL-1B-31 and the TNF-A-308 polymorphisms were determined by PCR-RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L-1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non-cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL-1B-31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73-46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8-50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05-161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL-1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC.

The association between cagA+ H. pylori infection and distal gastric cancer: a proposed model.

Cytotoxin-associated gene A (cagA)+ infection is associated with an increased risk of distal gastric cancer. The aim was to determine the effect of Helicobacter pylori (HP) on gastric mucus thickness, hydrophobicity, and PGE2 and their relation to colonization density. Ninety-nine patients were recruited (69 HP- and 30 HP+: 10 cagA+, 18 cagA-, 2 undetermined) and six biopsies were obtained from each patient. Mucus thickness, hydrophobicity, PGE2, and colonization density were determined. HP status was assessed by histology and culture; cagA+ was determined by PCR. In age- and sex-matched patients, PGE2 was greater in PH+ than HP- (P = 0.04), with cagA+ having higher PGE2 than HP- patients (P = 0.031). No differences were observed in mucus thickness (P = 0.717) or hydrophobicity (P = 0.27) between HP+ and HP- patients. However, cagA+ showed a nonsignificant trend of increase in mucus thickness (P = 0.784) and hydrophobicity (P = 0.30) compared to cagA- and HP- patients. cagA+ colonization density was weakly correlated with increased thickness (r = 0.333, P = 0.381), whereas cagA- density was inversely correlated with thickness (r = -0.805, P = 0.0001). A model suggesting the possible changes induced by cagA+ infection is proposed which explains the high association of cagA+ with distal gastric cancer. If supported by large multicenter studies, this could form the basis for the development of new therapies directed at the mucous layer to eradicate HP and thus reduce the risk of gastric cancer.

CagA+ Helicobacter pylori induces greater levels of prostaglandin E 2 than cagA− strains

cagA+ Helicobacter pylori (HP) infection is associated with an increased risk of distal gastric cancer. Previous studies investigating the effect of HP infection on prostaglandin E 2 (PGE 2) levels have not differentiated between cagA+ and cagA− strains and consequently have produced contradictory results. The aim was to investigate the effect of cagA+ strains on PGE 2 and enhance the understanding of the mechanisms leading to gastric diseases. Hundred patients without peptic ulcers and not on medication were recruited (one later excluded) from endoscopy clinics: six biopsies were obtained from each patient. PGE 2, colonization density and histology were determined. In addition, HP status was assessed by histology, CLOtest and culture with cagA+ being determined by PCR. Sixty-nine patients were HP− and 30 HP+ (10 cagA+, 18 cagA−, 2 undetermined). In age and sex-matched patients, PGE 2 was significantly greater ( P=0.04) in HP+ (37.2±1.2 pg/mg per 20 min) than in HP− (22.6±1.2). In patients without atrophy, those infected with cagA+ had significantly higher ( P=0.03) PGE 2 levels (53±1.1) than HP−patients (22.6±1.1) and greater levels ( P=0.29) than cagA− patients (35±1.3). In conclusion, the increased levels of PGE 2 in the presence of cagA+ infection could be an important factor by which cagA+ strains enhance the gastric mucus layer protective functions leading to established colonization, gastritis and increased risk of gastric cancer. However, further evaluation with a large-scale multi-centre study is required to substantiate this hypothesis.

This month in gastroenterology

This month in gastroenterology

Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa

Background & Aims : Helicobacter pylori strains that possess the cag pathogenicity island ( cag +) augment the risk for distal gastric cancer. Matrix metalloproteinase (MMP)-7, an epithelial cell-derived MMP that is induced by bacterial contact, is overexpressed within human gastric adenocarcinoma specimens and enhances tumor formation in rodents. We determined whether H. pylori alters MMP-7 expression and investigated the molecular pathways required for these events. Methods : MMP-7 was detected in human gastric mucosa by immunohistochemistry and in H. pylori/AGS gastric epithelial cell coculture supernatants by Western analysis. AGS cells were cocultured with wild-type H. pylori, or isogenic cagA −, cagE −, or vacA − mutants, in the absence or presence of inhibitors of nuclear factor κB activation, p38, or extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase. Results : H. pylori cag + strains increased MMP-7 expression in AGS cells 5–7-fold, whereas cag − isolates had no effect. Inactivation of cagE, but not cagA or vacA, completely attenuated induction of MMP-7, and inhibition of ERK 1/2 decreased MMP-7 production. In vivo, MMP-7 was expressed in gastric epithelial cells in specimens from 80% of cag +-colonized persons but in none of the cag − or uninfected subjects. Conclusions : H. pylori cag + strains enhance levels of MMP-7 within inflamed mucosa. In vitro, cag + isolates selectively induce MMP-7, and this is dependent on activation of ERK 1/2 by specific components within the cag island. Differential induction of MMP-7 by H. pylori cag + isolates may explain in part the augmentation in gastric cancer risk associated with these strains.

Assessment of Helicobacter pylori prevalence in a community with high risk for distal gastric cancer

Assessment of Helicobacter pylori prevalence in a community with high risk for distal gastric cancer

The phenotype of gastric mucosa coexisting with Barrett's oesophagus

Background/Aims—Barrett's oesophagus complicates the gastro-oesophageal acid reflux. Helicobacter pylori infection, particularly with cagA positive strains, induces inflammatory/atrophic lesions of the gastric mucosa, which may impair acid output. No systematic study...

Pro-inflammatory genotypes of IL-1β, TNF-α and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinomas

Pro-inflammatory genotypes of IL-1β, TNF-α and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinomas

Pro-inflammatory genotypes of IL-1β, TNF-α and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinomas

Pro-inflammatory genotypes of IL-1β, TNF-α and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinomas