Risk Of Noncardia Gastric Adenocarcinoma Research Articles

Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United States

High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population. We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios. Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years. In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication.

Abstract 737: Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

Abstract Background: Certain diet components (i.e. low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with risk of gastric cancer. However, it is unclear whether overall diet quality assessed by pre-defined indices, that take into account the complexity of dietary intake, is associated with gastric cardia and distal adenocarcinoma particularly in a racially and ethnically diverse population. Our objectives are to 1) examine the association of a variety of diet quality indices with risk of gastric cardia and distal adenocarcinoma and 2) assess if there are any subgroups that may benefit from better diets to reduce risk of gastric adenocarcinoma. Methods: The analysis included 176,752 men and women aged 45-75 from the Multiethnic Cohort (MEC), who were African American, Japanese American, Latino, Native Hawaiian, or White, and completed a quantitative food frequency questionnaire (QFFQ) at cohort entry. Incident cases of gastric cancer (cardia ICD-O-3 C16.0 and non-cardia adenocarcinoma C16.1-C16.6) were identified by linkages with the Surveillance, Epidemiology, and End Results (SEER) cancer registries. Dietary indices, Alternative Healthy Index-2010 (AHEI-2010), Healthy Eating Index-2015 (HEI-2015), Dietary Approach to Stop Hypertension (DASH) score, alternate Mediterranean Diet (aMED) score, and Dietary Inflammatory Index (DII®), were calculated from the QFFQ and categorized into quintiles. Multivariable Cox models were used to estimate the association between dietary indices and gastric cancer risk by anatomic site. Effect modification was assessed for distal cancer by sex, smoking status, and aspirin use. Results: A total of 207 incident cases of gastric cardia and 836 incident cases of gastric non-cardia were identified during an average follow up of 19.2 years. We did not observe any significant associations between any of the dietary indices and gastric cancer for both cardia and non-cardia tumors. However, we observed effect modification by aspirin use for aMED (P for heterogeneity = 0.01) as well as for DII (P for heterogeneity = 0.02). Among ever aspirin users, we observed an inverse association between aMED (HRQ5 vs Q1: 0.82, 95% CI: 0.53-1.26, Ptrend = 0.03) with non-cardia cancer, and the association with DII® was borderline statistically significant for the trend test (HRQ5 vs Q1: 0.86, 95% CI: 0.57-1.29, Ptrend = 0.07). Conclusion: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among ever aspirin users there could be a reduction of gastric non-cardia adenocarcinoma risk with a higher adherence to a Mediterranean diet. Citation Format: Nicholas Acuna, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, V. Wendy Setiawan. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 737.

Inverse Association Between Gluteofemoral Obesity and Risk of Non-Cardia Gastric Intestinal Metaplasia

It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia. We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric biopsy. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. Increasing body mass index (BMI) was not associated with risk of non-cardia gastric intestinal metaplasia (per unit BMI adjusted OR, 0.98; 95% CI, 0.96-1.00). Similarly, we found no associations with increase in waist circumference (per 10-cm increase adjusted OR, 0.94; 95% CI, 0.87-1.03) and waist-to-hip ratio (WHR) (per unit WHR adjusted OR, 2.34; 95% CI, 0.37-14.7). However, there was a significant inverse association with gastric intestinal metaplasia and increasing hip circumference, reflecting gluteofemoral obesity (per 10-cm increase adjusted OR, 0.89; 95% CI, 0.80-0.98). The inverse association was observed for both extensive and focal gastric intestinal metaplasia. The independent dimensions of adiposity (BMI, waist circumference) are not associated with increased risk of non-cardia gastric intestinal metaplasia. The inverse association between gluteofemoral obesity and risk of gastric intestinal metaplasia warrants additional study.

731 RISK OF ESOPHAGEAL AND GASTRIC ADENOCARCINOMA IN MEN RECEIVING ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

Abstract There is an unexplained male predominance in the incidence of esophageal (EAC) and non-cardia gastric adenocarcinoma (GAC) which cannot be explained by known risk factors. Differences in the exposures to sex hormones may play a part in the observed sex difference. This study aimed to test the hypothesis that androgens increase the risk of EAC, cardia GAC, and non-cardia GAC. We analysed a matched cohort based on a national Swedish database of prostate cancer patients. Methods Prostate cancer patients receiving androgen deprivation therapy (ADT) were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios and 95% confidence intervals were adjusted for confounders. Results There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). Conclusion This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

Risk of esophageal and gastric adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer

The aim of this study was to explore the male predominance in esophageal and gastric adenocarcinoma by evaluating the preventive potential of androgen deprivation therapy (ADT). This matched cohort study was based on a national Swedish database of prostate cancer patients in 2006–2013. Prostate cancer patients receiving ADT were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for confounders. There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

Population-Based Analysis of Differences in Gastric Cancer Incidence Among Races and Ethnicities in Individuals Age 50 Years and Older

There are racial and ethnic differences in the incidence of gastric adenocarcinoma worldwide and in the US. Based on a decision analysis, screening for noncardia gastric adenocarcinoma might be cost-effective for non-White individuals 50 years or older. However, a lack of precise, contemporary information on gastric adenocarcinoma incidence in specific anatomic sites for this age group has impeded prevention and early detection programs in the US. We aimed to estimate the differences in gastric adenocarcinoma incidence in specific anatomic sites among races and ethnicities in individuals 50 years or older. We analyzed California Cancer Registry data from 2011 through 2015 to estimate incidences of gastric adenocarcinoma in specific anatomic sites for non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 7 largest Asian American populations. We calculated the differential incidence between non-White groups and NHW using incidence rate ratios and 95% confidence intervals (CIs). Compared with NHW subjects, all non-White groups had significantly higher incidences of noncardia gastric adenocarcinoma; the incidence was highest among Korean American men 50 years and older (70 cases per 100,000). Compared with NHW subjects 50 years and older, the risk of noncardia gastric adenocarcinoma was 1.8-fold (95% CI, 1.37-2.31) to 7.3-fold (95% CI, 5.73-9.19) higher in most non-White groups and 12.0-fold (95% CI, 9.96-14.6) to 14.5-fold (95% CI, 12.5-16.9) higher among Korean American men and women 50 years and older, respectively. Compared with NHW men 50 years and older, all non-White men, except Japanese and Korean American men, had a significantly lower risk of cardia gastric adenocarcinoma. We identified several-fold differences in incidences of gastric adenocarcinoma in specific anatomic sites among racial and ethnic groups, with significant age and sex differences. These findings can be used to develop targeted risk reduction programs for gastric adenocarcinoma.

Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study

BackgroundWhether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear.MethodsThis was a population-based cohort study in 2005–2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins.ResultsDuring the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78–1.12; matched cohort: HR 1.30, 95% CI 1.18–1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09–2.02; matched cohort: HR 1.58, 95% CI 1.38–1.81) compared with non-users in both cohorts.ConclusionsThis cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.

Mediterranean diet adherence and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

BackgroundMediterranean diet (MD) adherence has been associated with reduced risks of esophageal and gastric cancer (subtypes) in a limited number of studies. We prospectively investigated associations between MD adherence and risks of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in a Dutch cohort.MethodsAnalyses were conducted using data from the 120852 participants of the Netherlands Cohort Study (NLCS), who were aged between 55 and 69 years at enrollment. Various MD scores, with and without alcohol, were calculated to estimate MD adherence. Using 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases could be included in multivariable Cox regression analyses.ResultsOf the investigated scores, the alternate Mediterranean diet score without alcohol (aMEDr) performed best. aMEDr was inversely associated with risks of GCA and GNCA in men and women. However, statistical significance was only reached in men [ptrend: 0.019 (GCA), 0.016 (GNCA)]. Furthermore, higher aMEDr values were significantly associated with a reduced ESCC risk in men [HRper two−point increment (95% CI) = 0.57 (0.41–0.80), ptrend = 0.013], but not in women (pheterogeneity = 0.008). There was no evidence of an association between aMEDr and EAC risk. Educational level was a significant effect modifier for the association between aMEDr and GNCA risk (pheterogeneity = 0.0073).ConclusionsHigher MD adherence was associated with reduced risks of ESCC, GCA, and GNCA in the NLCS. However, the decreased ESCC risk might be limited to men.

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

The role of alcoholic beverages in the etiology of gastric cancer is unclear. Recent summaries showed a positive association between higher alcohol intake and gastric cancer risk, but the magnitude of association is small, there is moderate heterogeneity among studies, and most cases were from Asian populations. We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in 490,605 adults, aged 50-71 years at baseline who participated in the NIH-AARP diet and health study. Alcohol consumption in the past year was assessed at baseline by questionnaire and defined as total grams of ethanol intake per day or as a categorical variable: nondrinker, up to or including one drink per day, one to three drinks per day and greater than three drinks per day. We used multivariable-adjusted Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for associations between alcohol intake and risk of gastric adenocarcinomas. Through 2011, 662 incident cases of GCA and 713 of GNCA occurred. We found no association between higher alcohol consumption and GCA or GNCA, when examined as total alcoholic beverage intake or individual beverage types of beer, wine and liquor. Furthermore, we observed no association by stratum of sex, ethnic group, educational level or smoking status. We did, however, observe lower risk of GNCA among participants who drank up to one drink per day (HR = 0.81, 95% CI: 0.67-0.97) compared to nondrinkers. In conclusion, alcohol consumption was not associated with increased risk of GCA or GNCA in this large U.S. cohort.

Abstract 5260: Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort

Abstract Objective: The 2016 WCRF Continuous Update Project reported that consumption of alcoholic drinks probably causes gastric cancer, but the magnitude of the association was small, there was moderate heterogeneity among the studies included in the meta-analysis, and most studies were from Asian populations, with only 401 cases from North American studies. Therefore, we re-evaluated the association between alcohol intake and gastric cancer in a large US cohort that has accrued more than 1300 gastric cancer cases. Methods: We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in 490,605 members aged 50-71 years at baseline in the NIH-AARP Diet and Health Study cohort. Alcohol consumption was assessed during the baseline questionnaire in 1995/1996 and evaluated as grams of ethanol intake and as a categorical variable: never, up to or including one drink/day, one to three drinks/day, and greater than three drinks/day. We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals for associations between alcohol intake and risk of gastric adenocarcinomas with adjustment for several potential confounders. Results: Through 2011, 662 incident cases of GCA and 713 of GNCA occurred in the cohort. We found no association between higher alcohol consumption and GCA or GNCA, regardless of whether analyzed as total alcoholic beverage intake or the individual beverage types of beer, wine and liquor and no evidence for a dose-response. Furthermore, we observed no association by stratum of sex, ethnic group, educational level, or smoking status. Although there were no overall associations, we found some evidence for lower risk of GNCA among people who drank up to one drink per day (HR=0.81, 95%CIs:0.67-0.97) compared to nondrinkers. Conclusion: Alcohol consumption was not associated with increased risk of gastric cardia adenocarcinoma or gastric non-cardia adenocarcinoma in this large US prospective cohort. Citation Format: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5260.

Tree nut, peanut, and peanut butter consumption and the risk of gastric and esophageal cancer subtypes: the Netherlands Cohort Study

BackgroundNut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study.MethodsIn 1986, 120,852 males and females, aged 55–69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case–cohort approach.ResultsIncreased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30–0.96) and 0.73 (0.55–0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse.ConclusionsOur findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.

Serum gastrin and cholecystokinin are associated with subsequent development of gastric cancer in a prospective cohort of Finnish smokers.

Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish smokers. Totals of 283 incident GNCA, 96 EGJA and 10 gastric carcinoid cases, and 778 matched controls, were included in our analysis. Gastrin and CCK were measured using specific radioimmunoassays. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by multivariable logistic regression with adjustment for all known or suspected confounding factors, including Helicobacter pylori seropositivity. Those with high gastrin (Q4 vs Q1), had an increased risk of GNCA (fully adjusted OR: 1.92; 95% CI: 1.21, 3.05) and gastric carcinoids, though the small number of carcinoid cases meant the fully adjusted model was unstable (age-adjusted continuous model OR: 4.67; 95% CI: 2.67, 8.15). CCK was associated with risk of GNCA only for those in Q3 relative to Q1 (OR: 0.56; 95% CI: 0.33, 0.96), and no significant trend was observed. Our data suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear.

Nut and peanut butter consumption and the risk of esophageal and gastric cancer subtypes

Background: Nut consumption has been associated with decreased risk of colorectal, endometrial, lung, and pancreatic cancers. Polyphenols, fiber, vitamins, and minerals in nuts may confer this observed protective effect. To our knowledge, no prospective study has evaluated the effect of nut consumption on esophageal and gastric cancers.Objective: The objective was to evaluate the associations between nut and peanut butter consumption and the risk of esophageal and gastric cancers and their different subtypes.Design: In this study we used data from the NIH-AARP Diet and Health Study, which enrolled 566,407 persons who were 50-71 y old at baseline (1995-1996). The median follow-up time was 15.5 y. Intakes of nuts and peanut butter were assessed through the use of a validated food-frequency questionnaire. We used Cox proportional hazard models to estimate HRs and 95% CIs for esophageal and gastric cancers and their subtypes.Results: We identified 966 incident cases of esophageal adenocarcinomas, 323 cases of esophageal squamous cell carcinoma, 698 cases of gastric cardia adenocarcinoma, and 732 cases of gastric noncardia adenocarcinoma. Compared with those who did not consume nuts or peanut butter [lowest category of consumption (C0)], participants in the highest category of nut consumption (C3) had a lower risk of developing gastric noncardia adenocarcinoma [C3 compared with C0, HR: 0.73 (95% CI: 0.57, 0.94)]. This inverse association was also seen for peanut butter consumption [C3 compared with C0, HR: 0.75 (95% CI: 0.60, 0.94)]. We observed no significant associations between the highest and lowest intakes of nuts or peanut butter and the risk of gastric cardia adenocarcinoma, esophageal adenocarcinoma, or esophageal squamous cell carcinoma.Conclusions: Among older American adults, both nut and peanut butter consumption were inversely associated with the risk of gastric noncardia adenocarcinoma. This trial was registered at clinicaltrials.gov as NCT00340015.

Dietary Flavonols Intake and Risk of Esophageal and Gastric Cancer: A Meta-Analysis of Epidemiological Studies.

Background: Esophageal cancer (EC) and gastric cancer (GC) are common cancers and leading causes of cancer deaths worldwide. Many studies have investigated the association between dietary flavonols intake and the risk of EC and GC, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to assess the association and derive a more precise estimation. Methods: The Cochrane, PubMed and Embase databases were searched to identify articles published through January 2016 that met the predetermined inclusion criterion. Twelve studies involving 4593 patients and 519,378 controls were included. Results: The summary odds ratios (ORs) of EC, GC and the two combined were respectively 0.88 (95% CI: 0.73–1.08), 0.80 (95% CI: 0.70–0.91) and 0.83 (95% CI: 0.74–0.92) for the highest category of dietary flavonols intake compared with the lowest. No significant heterogeneities were observed in these studies. Further analysis showed that the pooled ORs of EC and GC for cohort, population-based case-control and hospital-based case-control studies were 0.90 (95% CI: 0.61–1.34), 0.92 (95% CI: 0.72–1.18), 0.68 (95% CI: 0.38–1.24) and 0.83 (95% CI: 0.65–1.06), 0.84 (95% CI: 0.45–1.59), 0.70 (95% CI: 0.56–0.88). The subgroup analyses revealed a significant association of flavonol intake with a reduced risk of noncardia gastric adenocarcinoma but not gastric cardia adenocarcinoma. Moreover, significant inverse associations of flavonol intake with GC risk were observed in women but not in men, in smokers but not in nonsmokers, in European populations but not in American populations. Similarly, a significant inverse association of flavonols intake with EC risk was also observed in smokers but not in nonsmokers. Conclusion: High intake of dietary flavonols is significantly related to a reduced risk of GC, especially in women and smokers.

A Prospective Study of Vitamin and Mineral Supplement Use and the Risk of Upper Gastrointestinal Cancers

We examined the association of use of multivitamins or single vitamin/mineral supplements with risk of four upper gastrointestinal cancers in the NIH-AARP Diet and Health Study cohort with 11 years of follow-up. After exclusions, 490,593 persons were included in our analytic cohort and 1780 upper gastrointestinal cancers were accrued. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox models with adjustment for potential confounders. We observed no significant associations between multivitamin use and risk for the four cancer outcomes in crude or adjusted models. Among individual vitamin or mineral supplements, use of iron supplements was associated with significantly lower risk of esophageal adenocarcinoma (HR = 0.68, 95% CI = 0.49 to 0.94) and a significantly increased risk of gastric noncardia adenocarcinoma (HR = 1.59, 95% CI = 1.24 to 2.05). For gastric noncardia adenocarcinoma, we saw associations with zinc use (HR = 1.28, 95% CI = 1.01 to 1.62) and vitamin C use (HR = 0.79 95% CI = 0.65 to 0.96). Calcium use, some of which was reported as antacids and used to treat reflux disease, was associated with higher risk of esophageal adenocarcinoma (HR = 1.27, 95% CI = 1.06 to 1.52) and gastric cardia adenocarcinoma (HR = 1.27, 95% CI = 1.03 to 1.56) cancers. We saw no evidence that multivitamin use was associated with reduced risk of four highly fatal upper gastrointestinal cancers, but there were some differences in risk with reported use of individual supplements.

Physical Activity and Sedentary Behavior in Relation to Esophageal and Gastric Cancers in the NIH-AARP Cohort

IntroductionBody mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). MethodsSelf-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI) ResultsDuring 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR>5 times/week vs. never=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15–18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR5–6 hrs/day vs. <1 hr=0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. ConclusionsWe find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior.

Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

Abstract A99: Dietary N-nitroso compounds, endogenous nitrosation and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Abstract Background: Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but evidence for their role from population studies is scarce for esophageal, and inconsistent for gastric cancer. Objective: We studied the relationship between the risk of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite and nitrate in The Netherlands Cohort Study. Methods: 120 852 men and women aged 55-69 years were recruited in 1986, and diet, based on a 150-item food frequency questionnaire, as well as other risk factors were assessed. The cohort was followed for 16.3 years, and 110 esophageal squamous cell carcinomas, 151 esophageal adenocarcinomas, 166 gastric cardia adenocarcinomas, and 497 gastric non-cardia adenocarcinoma cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Results: There were positive associations between N-nitrosodimethylamine intake and esophageal squamous cell carcinoma and gastric non-cardia adenocarcinoma risk in men (hazard ratio (HR) for 0.1 μg/day increase in intake: 1.15 [95% confidence interval (CI): 1.05-1.25; P(trend): 0.01] and 1.06 [95%CI: 1.01-1.10; P(trend): 0.09], respectively). Esophageal squamous cell carcinoma risk was associated with nitrite and heme iron intake (HR for 0.1 mg/day increase in nitrite intake: 1.19 [95%CI: 1.05-1.36; P(trend): 0.06] and for 1 mg/day heme iron intake: 1.83 [95%CI: 0.98-3.39; P(trend): 0.03]). Among women, exposure levels were lower, and we found a positive association only between N-nitrosodimethylamine and esophageal squamous cell carcinoma risk (HR for 0.1 μg/day increase: 1.34 [95%CI: 1.04,1.71; P(trend):0.57]). Conclusion: These results suggest that N-nitroso compounds and their precursors may influence the risk of esophageal squamous cell carcinoma. Citation Format: András P. Keszei, R Alexandra Goldbohm, Leo J. Schouten, Paula Jakszyn, Piet A. van den Brandt. Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A99.

Interleukin-4 receptor −3223C→T Polymorphism is Associated with Increased Gastric Adenocarcinoma Risk

Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations. To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1b -511C→T [rs16944], IL-4 receptor [IL-4R] -3223C→T [rs2057768], IL-8 -251T→A [rs4073], IL-10 -1082A→G [rs1800896] and tumour necrosis factor-alpha -308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population. A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the chi squared&nbsp;test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI. A significant association between the IL-4R -3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R -3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R -3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms. The results suggest that the IL-4R -3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.

Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54-0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21-0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.