Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary ...folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, OR
= 1.15 (95% CI, 0.85-1.56), and the OR
= 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.
Abstract
Introduction: Consumption of fruits, vegetables and fiber has been associated with lower colorectal cancer (CRC) risk however, it is unclear if genetic variants can modify these ...associations.
Methods: Within three genetic CRC consortia including up to 76,157 participants (32,859 cases and 43,298 controls) of European descent: the Colorectal Cancer Family Registry (CCFR), the Colorectal Cancer Transdisciplinary (CORECT) Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), one-step logistic regression case-control analysis and joint two- and three-degrees of freedom (DF) tests and two-step methods were implemented to identify novel and biologically plausible gene-environment interactions.
Results: Fruits, vegetables and fiber consumption were inversely associated with CRC with odds ratios per quartile increase of 0.89 95% confidence interval (CI): 0.86, 0.92, 0.91 (95% CI: 0.88, 0.94) and 0.86 (95% CI: 0.84, 0.89) respectively. The logistic regression analysis identified significant interaction effects between rs142981275 adjacent to the ACOT1 gene and fruits consumption (pval:1.91E-8) and the 2DF test, which jointly considers G and GxE effects, also identified this SNP. The 3DF test also considers G and GxE information and further revealed four loci associated with CRC risk, in the genes NEGR1(rs1620977), ZRANB3 (rs1561277), MCM6 (rs4988235), R3HDM1(rs12465802) (all pval:<5E-8) out of which rs1620977 and rs12465802 were the leading independent variants. For vegetables, the 3DF test identified significant interaction effects in the DCBLD1 gene (rs4946259; pval:1.44E-8). Finally, no significant interactions were observed for any genetic variant and fiber consumption. The 2-step approach did not identify additional interactions either.
Conclusion: This study identified statistically significant interactions between several genetic variants and the consumption of fruits and vegetables with CRC risk. Further research is needed to elucidate the exact mechanisms through which these interactions might influence CRC risk.
Citation Format: Nikos Papadimitriou, Akihisa Hidaka, Andre Kim, Niki Dimou, Neil Murphy, Sonja I. Berndt, David Conti, Peter T. Campbell, Graham Casey, Jane C. Figueiredo, Konstantinos K. Tsilidis, Stephen B. Gruber, Sophia Harlid, Yi Lin, Victor Moreno, Lori C. Sakoda, Virginia D. Obrero, Li Hsu, William J. Gauderman, Marc Gunter, Ulrike Peters. Consumption of fruits, vegetables and fiber and risk of colorectal cancer: A gene environment interaction analysis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 819.
The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated ...with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population‐based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person‐years of follow‐up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5‐kg/m2 increase 0.57, 95% CI 0.50–0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00–1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m2) relative to BMI <25 kg/m2 was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80–2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05–1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study—the largest in an Asian country—provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype‐ or subsite‐specific carcinogenic impact of BMI in a Japanese population.
The impact of BMI on upper gastrointestinal cancer by subtype or subsite among Asians is inconclusive. Using data from 10 large‐scale population‐based cohort studies, we evaluated the association between BMI and upper gastrointestinal cancers for 394,247 Japanese individuals. With 1038 esophageal squamous cell carcinoma, 86 esophageal adenocarcinoma, 728 gastric cardia cancer, and 5620 gastric noncardia cancer cases, we confirmed the subtype‐ or subsite‐specific carcinogenic impact of BMI in an Asian population.
Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is ...that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in
and
genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of
-mutated tumors OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04) but not
-wildtype tumors 1.09 (0.97-1.22);
difference as shown in case-only analysis = 0.02. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative,
-wildtype, and
-wildtype tumors (
range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive,
-mutated, or
-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.
The role of allium vegetables on gastric cancer (GC) risk remains unclear.
We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies ...participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach.
Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I
> 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata.
In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.
Diets rich in vegetables and fruit have been associated with reduced risk of gastric cancer, and there is suggestive evidence that citrus fruits have a protective role. Our study aimed at evaluating ...and quantifying the association between citrus fruit intake and gastric cancer risk. We conducted a one‐stage pooled analysis including 6,340 cases and 14,490 controls from 15 case–control studies from the stomach cancer pooling (StoP) project consortium. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer across study‐specific tertiles of citrus fruit intake (grams/week) were estimated by generalized linear mixed effect models, with logistic link function and random intercept for each study. The models were adjusted for sex, age, and the main recognized risk factors for gastric cancer. Compared to the first third of the distribution, the adjusted pooled OR (95% CI) for the highest third was 0.80 (0.73–0.87). The favourable effect of citrus fruits increased progressively until three servings/week and leveled off thereafter. The magnitude of the association was similar between cancer sub‐sites and histotypes. The analysis by geographic area showed no association in studies from the Americas. Our data confirm an inverse association between citrus fruits and gastric cancer and provide precise estimates of the magnitude of the association. However, the null association found in studies from America and in some previous cohort studies prevent to draw definite conclusions on a protective effect of citrus fruit consumption.
What's new?
The association between citrus fruit intake and cardia cancer was classified as limited/suggestive, whereas no conclusions could be drawn on non‐cardia cancer. Our pooled analysis within a global consortium of case‐control studies indicates and quantifies a protective effect of citrus fruits on both cardia and non‐cardia cancers.
Abstract
Background
Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to ...determine the association between occupations/occupational exposures and odds of gastric cancer.
Methods
We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders.
Results
A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06–1.68; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01–2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05–1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06–1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41–30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01–2.26) for intestinal-type and 2.52 (95% CI: 1.46–4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09–3.06) and 2.92 (95% CI: 1.36–6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer.
Conclusions
Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation.
Background
Helicobacter pylori is the most important risk factor for non‐cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study ...aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status.
Methods
A pooled analysis of individual‐level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti‐Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two‐stage approach was used to pool study‐specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta‐analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted.
Results
The OR for the association between serology‐defined H. pylori and NCGC was 1.45 (95% CI: 0.87–2.42), which increased to 4.79 (95% CI: 2.39–9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region—a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22–4.07) for ELISA or EIA and 9.22 (95% CI: 3.12–27.21) for immunoblot or multiplex serology.
Conclusion
The NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.
Background: Most previous prospective studies in Western countries found no association between consumption of fish and n–3 (ω-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid ...(EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), for which the main source is fish, and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption.
Objective: We investigated the association between fish and n–3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women.
Design: The Japan Public Health Center–based Prospective Study (JPHC study) has enrolled 140,420 subjects. We analyzed data on 82,024 eligible participants aged 45–74 y without a history of cancer who responded to a validated food-frequency questionnaire that included 138 items in 1995 for cohort I and in 1998 for cohort II. Participants were followed through 2010. HRs and corresponding 95% CIs for the highest compared with lowest quartile were calculated by using multivariable-adjusted Cox proportional hazards regression models.
Results: During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. After the exclusion of pancreatic cancer cases in the first 3 y of follow-up, we found an inverse association of marine n–3 PUFA (EPA+DPA+DHA) and DHA consumption with pancreatic cancer risk: compared with the lowest quartile, multivariate-adjusted HRs in the highest quartile were 0.70 (95% CI: 0.51, 0.95; P-trend = 0.07) and 0.69 (0.51, 0.94; P-trend = 0.03), respectively. Associations for total fish, n–3 PUFA, EPA, and DPA consumption were similar but were not significant.
Conclusion: High n–3 PUFA, especially marine n–3 PUFAs, and DHA consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption, although the data apply to only a portion of the JPHC study subjects.
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