Sequence variants in antioxidant defense and DNA repair genes, dietary antioxidants, and pancreatic cancer risk.

To investigate whether polymorphisms in genes related to oxidative stress act alone or in combination with antioxidants to modulate pancreatic cancer risk. Cases (n=189), ages ≥ 20 years, were ascertained in 1994-1998 from all hospitals in the Twin Cities and the Mayo Clinic. Controls (n=486) were randomly selected from the general population and frequency matched to cases by age and sex. After adjustment for confounders, individuals who were homozygous or heterozygous for the variant allele of SOD2 polymorphism (Ala16Val, rs4880) experienced a 43% lower risk than those who were homozygous for the wild-type allele [OR (95% CI): 0.57 (0.37, 0.89)]. Conversely, an increased risk was observed for the variant allele of hOGG1 polymorphism (Ser326Cys, rs1052133) compared with the wild-type allele [OR (95% CI) for Ser/Cys or Cys/Cys vs. Ser/Ser: 1.57 (1.04, 2.39)]. The protective effect of the variant allele of SOD2 was more pronounced among subjects with a low dietary intake (<median) of lutein/ zeaxanthin, lycopene, α-carotene, and α-tocopherol [OR (95% CI): 0.46 (0.27, 0.81), 0.42 (0.23, 0.75), 0.47 (0.26, 0.85), and 0.48 (0.27, 0.87), respectively]. Individual variations in the capacity to defend against oxidative stress and to repair oxidative DNA damage influence pancreatic cancer risk, and some of these genetic effects are modified by dietary antioxidants.