Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer

Purpose To carry out pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). The impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. The risk of EA increased with increasing GERD/BMI score, and the risk of ESCC rose with increasing smoking/alcohol score and decreasing gastroesophageal reflux disease (GERD)/body mass index (BMI) score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with an elevated risk of each cancer under study, whereas fruit/vegetable intake reduces the risk of EA, ESCC, and GCA. GERD/obesity was confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC

Food group intake and risk of subtypes of esophageal and gastric cancer

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non‐cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population‐based case–control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High‐fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high‐fat dairy was associated with increased risk of gastric cardia adenocarcinoma

Food group intake and risk of subtypes of esophageal and gastric cancer

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non‐cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population‐based case–control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High‐fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high‐fat dairy was associated with increased risk of gastric cardia adenocarcinoma

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.This work was supported by the National Institutes of Health [R01CA136725 to T.L.V. and D.C.W, T32CA009168 to T.L.V, and K05CA124911 to T.L.V.]. Additional funding sources for individual studies included in the BEACON GWAS, and for BEACON investigators, have been acknowledged previously (16).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.012861

IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas

The mannose 6 phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypothesis that the common non-synonymous genetic variants in M6P/IGF2R c.901C>G (Leu>Val) in exon 6 and c.5002G>A (Gly>Arg) in exon 34 are associated with risk of esophageal and gastric cancers. Study participants in this population-based study comprise 197 controls and 182 cases, including 105 with esophageal-gastric cardia adenocarcinoma (EGA), 57 with non-cardia gastric adenocarcinoma and 20 with esophageal squamous cell carcinoma (ES). Among white males, odds ratios (ORs) were elevated in relation to carrying at least one c.901C>G allele for EGA (OR= 1.9; 95%CI=1.0–3.6) and non-cardia gastric cancer (OR=2.5; 95%CI=1.2–5.5), but not ES. Exploratory subgroup analyses suggested that associations between EGA and this variant were stronger among irregular or non-users of non-steroidal anti-inflammatory drugs (NSAIDs) (OR=2.3; 95%CI=1.2–4.2) and cigarette smokers (OR=2.1; 95%CI=1.0–4.2). An association between carrying the c.5002G>A genotype and EGA was not evident. These findings suggest that non-synonymous polymorphisms in M6P/IGF2R may contribute to the risks of EGA and non-cardia adenocarcinomas. Larger studies are required to confirm these findings

Nutrient Pathways and Breast Cancer Risk: The Long Island Breast Cancer Study Project

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we utilized interview data from a population-based sample of 1,463 breast cancer cases and 1,500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was employed to account for biologically plausible nutrient pathways (one-carbon metabolism, oxidative stress, glycemic control and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the one-carbon metabolism, oxidative stress and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer

Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancers: classification tree analysis

Although risk factors for squamous cell carcinoma of the esophagus (SCC) and adenocarcinomas of the esophagus (EA), gastric cardia (GC) and other (non-cardia) gastric sites (OG) have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancer

Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. METHODS: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for gene-environment interactions. RESULTS: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10-7). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03-34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), respectively. CONCLUSION: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.UK funding from MRC and Cancer Research U

Risk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization

Background & Aims Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). Methods We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett's and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. Results Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62–0.79 for men and OR, 0.57; 95% CI 0.40–0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62–0.77 for men and OR, 0.61; 95% CI, 0.48–0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. Conclusions Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification

Principal Component Analysis of Dietary and Lifestyle Patterns in Relation to Risk of Subtypes of Esophageal and Gastric Cancer

To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers