Abstract
Abstract Pancreatic cancer is one of the leading causes of cancer death in the US and other Western countries and has a dismal prognosis due to its fatal nature and lack of effective screening measures. Therefore, primary prevention is particularly important for this disease. However, the etiology of pancreatic cancer remains virtually enigmatic. Some epidemiologic studies have shown that dietary intake of antioxidants is inversely associated with the risk of pancreatic cancer, which are consistent with the constitutive expression of COX enzymes in normal tissue. This finding suggests that genetic variability in antioxidant defense and repair of oxidative DNA damage may modulate pancreatic cancer risk. We sought to investigate this hypothesis using data collected from a case-control study conducted during 1994-1998 in Minnesota. Cases (n=189), aged 20 years or older, were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic; from the latter, only cases residing in the Upper Midwest of the US were recruited. Controls (n=486) were randomly selected from the general population and frequency matched to cases by age (within 5 years) and sex. We genotyped polymorphisms in two antioxidant genes: catalase (CAT, −262C>T, rs1001179) and superoxide dismutase-2 (SOD2, Ala16Val, rs4880), and two DNA repair genes: human oxoguanine glycosylase 1 (hOGG1, Ser326Cys, rs1052133) and X-ray repair cross-complementing group 1 (XRCC1, Arg399Gln, rs25487). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. After adjustment for age, sex, race, education, cigarette smoking, and alcohol use, a protective effect [OR (95%CI): 0.66 (0.43-0.99)] was observed for the variant allele (Ala16Val) of SOD2, whereas a promoting effect [OR (95%CI): 1.51 (1.02-2.24)] was found for the variant allele (Ser326Cys) of hOGG1. It appeared that there were interactions between the above two polymorphisms and dietary intake of antioxidants (including supplements). The inverse relation with SOD2 (Ala16Val) was stronger for subjects with high intake of vitamin C (≥210 mg) [OR (95%CI): 0.51 (0.28-0.94)] or vitamin E (≥15 α- tocopherol equivalents) [OR (95%CI): 0.53 (0.29-0.96)]. Similarly, the positive relation with hOGG1 (Ser326Cys) was more pronounced among individuals with high intake of vitamin E (≥15 α- tocopherol equivalents) [OR (95%CI): 1.74 (0.99-3.05)]. Our study suggests that individual variations in capacities of antioxidant defense and repair of oxidative DNA damage influence pancreatic cancer risk; and these genetic effects are modified by dietary intake of antioxidants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1861.
Published Version
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