Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study.
Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (</=222) was stronger for smokers (OR, 1.44; 95% CI, 1.10-1.90). No significant association with prostate cancer was observed for polymorphic variants in SOD3 or SOD1. These results suggest that the Ala variant of SOD2 is associated with moderately increased risk of prostate cancer, particularly among men with lower intakes of dietary and supplemental vitamin E.
Kang
Daehee
D
Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea. dhkang@snu.ac.kr
Lee
Kyoung-Mu
KM
Park
Sue Kyung
SK
Berndt
Sonja I
SI
Peters
Ulrike
U
Reding
Douglas
D
Chatterjee
Nilanjan
N
Welch
Robert
R
Chanock
Stephen
S
Huang
Wen-Yi
WY
Hayes
Richard B
RB
D000368:Aged; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000975:Antioxidants / Q000008:administration & dosage; D016022:Case-Control Studies; D004032:Diet; D005091:Exons / Q000235:genetics; D016166:Free Radical Scavengers; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D014633:Valine / Q000235:genetics; D014810:Vitamin E / Q000008:administration & dosage; D044465:White People / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000409:Alanine; D000975:Antioxidants; D016166:Free Radical Scavengers; D007527:Isoenzymes; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014633:Valine; D014810:Vitamin E; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C441642:SOD3 protein, human