Polymorphisms in metabolism/antioxidant genes may mediate the effect of dietary intake on pancreatic cancer risk.
OBJECTIVE
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.
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.
Rick J
RJ
Jansen
Dennis P
DP
Robinson
Rachael Z
RZ
Stolzenberg-Solomon
William R
WR
Bamlet
XiangLin
X
Tan
Julie M
JM
Cunningham
Ying
Y
Li
David N
DN
Rider
Ann L
AL
Oberg
Kari G
KG
Rabe
Kristin E
KE
Anderson
Rashmi
R
Sinha
Gloria M
GM
Petersen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics; D004032:Diet / Q000009:adverse effects; D004043:Dietary Fiber / Q000008:administration & dosage; D004435:Eating; D002523:Edible Grain; D005260:Female; D005638:Fruit; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014675:Vegetables; D055815:Young Adult
D000975:Antioxidants; D004043:Dietary Fiber; D002374:Catalase