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The SOD2 Val / Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms
Author(s) -
Liu Geoffrey,
Zhou Wei,
Park Sohee,
Wang Lisa I.,
Miller David P.,
Wain John C.,
Lynch Thomas J.,
Su Li,
Christiani David C.
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20716
Subject(s) - xrcc1 , sod2 , genotype , odds ratio , lung cancer , medicine , allele , gastroenterology , oncology , confidence interval , minor allele frequency , superoxide dismutase , cancer research , single nucleotide polymorphism , biology , genetics , gene , oxidative stress
BACKGROUND Exogenous reactive oxygen species (ROS) induces DNA damage. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals, a major type of ROS, into hydrogen peroxide. p53 is a tumor suppressor gene, and X‐ray cross‐complementing group 1 (XRCC1) is involved in the base‐excision repair of ROS‐induced DNA damage. METHODS The authors investigated whether the SOD2 Ala16Val polymorphism modifies the associations between p53 Arg72Pro and XRCC1 Arg399Gln polymorphisms and the risk of nonsmall cell lung carcinoma (NSCLC) in a case–control study of 935 Caucasian patients with NSCLC and 1233 healthy control participants. The results were analyzed using logistic regression models that were adjusted for possible confounding variables. RESULTS There was no association between p53 or XRCC1 polymorphism and NSCLC risk for individuals with SOD2 Ala/Ala or Ala/Val genotype. For individuals with the SOD2 Val/Val genotype, greater risks were found in association with p53 (variant Pro allele vs. Arg/Arg ), XRCC1 (variant Gln allele vs. Arg/Arg ), and the combination of the two polymorphisms (“double variant” vs. “double wild type”), with the adjusted odds ratios (ORs) of 1.84 (95% confidence interval [95% CI], 1.20–2.82), 1.39 (95% CI, 0.98–2.21), and 2.54 (95% CI, 1.38–4.68), respectively. Furthermore, the greater risk for the double variant of p53 and XRCC1 in the SOD2 Val/Val genotype group was specific only for patients with adenocarcinoma and not for patients with squamous cell carcinoma, with adjusted ORs of 3.31 (95% CI, 1.68–6.51) and 0.69 (95% CI, 0.24–2.02), respectively. CONCLUSIONS The SOD2 Val/Val genotype may increase the risk of NSCLC carried by XRCC1 and p53 polymorphisms, particularly for adenocarcinoma. Cancer 2004. © 2004 American Cancer Society.