Original ArticlesPolymorphisms in Metabolism/Antioxidant Genes May Mediate the Effect of Dietary Intake on Pancreatic Cancer RiskJansen, Rick J. PhD, MS*; Robinson, Dennis P. MS†; Stolzenberg-Solomon, Rachael Z. PhD, RD‡; Bamlet, William R. MS†; Tan, XiangLin MD, PhD*; Cunningham, Julie M. PhD†; Li, Ying PhD†; Rider, David N. MSE†; Oberg, Ann L. PhD†; Rabe, Kari G. MS†; Anderson, Kristin E. PhD§; Sinha, Rashmi PhD∥; Petersen, Gloria M. PhD*Author Information From the Divisions of *Epidemiology, and †Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ‡Department of Epidemiology, National Institutes of Health, Bethesda, MD; §Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN; and ∥Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. Received for publication May 5, 2012; accepted March 13, 2013. Reprints: Rick J. Jansen, PhD, MS, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: Jansen.Rick@mayo.edu). This study was supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701) and the Molecular Cancer Genetic Epidemiology Training Program (R25 CA92049; funded by grant from the National Institutes of Health). The authors declare no conflict of interest. Pancreas: October 2013 - Volume 42 - Issue 7 - p 1043-1053 doi: 10.1097/MPA.0b013e3182968e00 Buy Metrics Abstract Objectives A source of variation for inconsistent dietary-pancreatic cancer associations may be individuals carrying constitutional metabolism/antioxidant gene variants that differentially benefit compared to homozygous individuals. Seventy-six tag single-nucleotide polymorphisms were genotyped in 13 candidate genes to test differential associations with pancreatic adenocarcinoma. Methods A clinic-based case-control design was used to rapidly ascertain 251 cases and 970 frequency matched controls who provided blood samples and completed a 144-item food frequency questionnaire. Single-nucleotide polymorphisms were evaluated using a dominant genetic model and dietary categories split on controls’ median intake. Logistic regression was used to calculate odds ratios and 95% confidence intervals, adjusted for potential confounders. Results Significant increased associations (Bonferroni corrected P ≤ 0.0007) were observed for carriers of greater than or equal to 1 minor allele for rs3816257 (glucosidase, α; acid [GAA]) and lower intake of deep-yellow vegetables (1.90 [1.28-2.83]); and carriers of no minor allele for rs12807961 (catalase [CAT]) and high total grains intake (2.48 [1.50–4.09]), whereas those with greater than or equal to 1 minor allele had a decreasing slope (across grains). The reference group was no minor alleles with low dietary intake. Conclusions Interindividual variation in metabolism/antioxidant genes could interact with dietary intake to influence pancreatic cancer risk. © 2013 by Lippincott Williams & Wilkins.