The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms.
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.
Liu
Geoffrey
G
Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Zhou
Wei
W
Park
Sohee
S
Wang
Lisa I
LI
Miller
David P
DP
Wain
John C
JC
Lynch
Thomas J
TJ
Su
Li
L
Christiani
David C
DC
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012907:Smoking; D013482:Superoxide Dismutase / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2
D004268:DNA-Binding Proteins; D013482:Superoxide Dismutase; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2; C000619371:XRCC1 protein, human