Functional Variant of Manganese Superoxide Dismutase (SOD2 V16A) Polymorphism Is Associated with Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Study

Abstract

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 (V222) 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. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1581-6)

Manganese-Superoxide Dismutase (MnSOD) Polymorphisms

“…The frequency distributions of C and T alleles were found to be respec- has the similar CC genotype frequency as seen in AfricanAmerican [35], Finn [36], and Italian populations [37]. We detected considerably lower CC genotype frequency than those found in Korean [38], Japan [39], Chinese [40] and Taiwan [41] populations and higher frequencies than those found in American [23], Polish [42], Danish [43], German [44] and Russian [45] populations. Eventually, CC genotype frequency in populations of the eastern countries, were lower (between 0-17%) found than the western countries (between 42-67%) ( Table 4).…”

“…SOD2 is a mitochondrial enzyme that catalyzes the formation of H 2 O 2 from superoxide radicals. The variant allele of SOD2 has been associated with elevated risk of breast [22], prostate [23], lung [24] and ovarian [25] cancers and non-Hodgkin's lymphoma [26].…”

Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

“…Briefly, of the 22 studies (Wang et al, 2001;Woodson et al, 2001;Lin et al, 2003;Liu et al, 2004;Wang et al, 2004;Li et al, 2005;Taufer et al, 2005;Ho et al, 2006;Choi et al, 2007;di Martino et al, 2007;Ergen et al, 2007;Kang et al, 2007;Arsova-Sarafinovska et al, 2008;Iguchi et al, 2008;Mikhak et al, 2008;Bica et al, 2009;Cheng et al, 2009;Iguchi et al, 2009;Sun et al, 2009;Zejnilovic etal., 2009), the sample size ranged between 100 and 3,030, and there were twelve studies on prostate cancer, four studies on esophageal cancer, and six studies on lung cancer. All studies, except for five of them (Taufer et al, 2005;Bica et al, 2009;Sun et al, 2009;Zejnilovic et al, 2009), indicated that the distribution of genotypes in the controls was consistent with HardyWeinberg equilibrium, while only one study conducted by Lin et al (2003) contained no data for Hardy-Weinberg equilibrium.…”

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

“…Associations between six single-nucleotide polymorphisms (SNPs) of the earlier-mentioned five genes and CRC have been reported in different ethnic groups (Smith et al, 2001;Landi et al, 2003Landi et al, , 2005Krzesniak et al, 2004;Jiang et al, 2005;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Berndt et al, 2006;Huang et al, 2006;Koh et al, 2006;Kuriki et al, 2006;Matsuo et al, 2006;Moreno et al, 2006;Theodoropoulos et al, 2006;Tranah et al, 2006;Hansen et al, 2007;Kang et al, 2007;Stern et al, 2007;Vogel et al, 2007;Yin et al, 2007;Kury et al, 2008;Funke et al, 2009;Khatami et al, 2009;Tsilidis et al, 2009;Yang et al, 2009;Engin et al, 2010;Meplan et al, 2010;Loh et al, 2011;Wu et al, 2011;Crous-Bou et al, 2012;Gil et al, 2012). These six variants comprised rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, rs4880 of SOD2, rs2228001 of XPC, and rs1801282 of PPARG.…”