title: Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer.
abstract: To test the hypothesis that polymorphic variants of antioxidant genes modify the risk of pancreatic cancer, we examined seven single-nucleotide polymorphisms (SNPs) of genes coding for superoxide dismutase (SOD) 2, glutathione S-transferase alpha 4 (GSTA4), catalase and glutathione peroxidase in 575 patients with pancreatic adenocarcinoma and 648 healthy controls in a case-control study. Information on risk factors was collected by personal interview and dietary information was collected by a self-administered food frequency questionnaire. Genotypes were determined using the Taqman method. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were estimated by unconditional logistic regression. No significant main effect of genotype was observed. A borderline significant interaction between diabetes and SOD2 Ex2+24T>C CT/TT genotype was observed (P(interaction) = 0.051); the AORs (95% CI) were 0.98 (0.73-1.32) for non-diabetics carrying the CT/TT genotype, 1.73 (0.94-3.18) for diabetics carrying the CC genotype and 3.49 (2.22-5.49) for diabetics carrying the CT/TT genotype compared with non-diabetics carrying the CC genotype. Moreover, the SOD2 -1221G>A AA genotype carriers had a significantly increased risk for pancreatic cancer among those with a low dietary vitamin E intake but decreased risk among those with a high vitamin E intake (P(interaction) = 0.002). There was a non-significant interaction between diabetes and GSTA4 Ex5-64G>A genotypes (P(interaction) = 0.078). No significant interaction between genotype with cigarette smoking or vitamin C intake was observed. These data suggest that genetic variations in antioxidant defenses modify the risk of pancreatic cancer in diabetics or individuals with a low dietary vitamin E intake.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M. D. Anderson Cancer Center, 1550 Holcombe Boulevard, Houston, TX 77030-4009, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Tang
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Dong
authors.forename: R Sue
authors.initials: RS
authors.lastname: Day
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage*; D048909:Diabetes Complications / Q000209:etiology*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D014810:Vitamin E / Q000008:administration & dosage*; D000099156:Superoxide Dismutase 2
chemical_list: D001205:Ascorbic Acid; D005982:Glutathione Transferase; D013482:Superoxide Dismutase; D014810:Vitamin E; D000099156:Superoxide Dismutase 2; C041116:leukotriene-C4 synthase