MnSOD Gene Polymorphism Association with Steroid-Dependent Cancer

Abstract

Oxidative stress enhances carcinogenesis due to DNA damage. Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism has been recently associated with breast and prostate cancer. The role of oxidative stress in male breast cancer is poorly investigated due to the low prevalence of this neoplasia. We studied the relationship between prostate cancer (PC), male (MBC) and female breast cancer (FBC) and this polymorphism in a case-control study. Human genetic polymorphism Val16Ala of MnSOD was obtained from blood and paraffin-embedded tumor samples. The polymorphism was determined in 11 cases of MBC, 51 cases of PC, 89 cases of FBC and 372 age-adjusted healthy controls by polymerase chain reaction-restriction fragment length polymorphism techniques using restriction enzyme Hae III. Chi-square or Fisher test were used to compare the MnSOD frequency distribution. The observed genotypic frequencies of all samples were AA = 9.6% (n = 50), VV = 25.4% (n = 133) and AV = 64% (n = 340), all at Hardy-Weinberg equilibrium. Breast and prostate cancer risk was elevated in male and female patients with the Ala/Ala genotype compared to controls (p = 0.006, odds ratio = 2.5, 95% confidence interval 1.393-4.541). Even though the frequency of the Ala allele was low (9.6%) in the studied population, these data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk both in males and females and also brings new information on the role of this polymorphism in prostate cancer. This is the first study which provides some evidence that genetic polymorphism in the MnSOD gene may be associated with an increased risk of male breast cancer. Studies with a larger sample size are needed to confirm the findings.

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.…”

“…In prostate cancer, we excluded three studies (Taufer et al, 2005;Ergen et al, 2007;Bica et al; because their controls were not in Hardy-Weinberg equilibrium and we found that the data did not statistically alter the conclusions of our analysis in the homozygote model (Ala/ Ala versus Val/Val, OR = 1.13; 95% CI = 1.01-1.27) or dominant model (Val/Ala+Ala/Ala versus Val/Val, OR = 1.11; 95% CI = 1.01-1.22). In the subgroup analysis by disease stages, one study (Wang et al, 2001) was excluded because the control was not in Hardy-Weinberg equilibrium.…”

There is no relationship between SOD2 Val-16Ala polymorphism and breast cancer risk or survival

“…In the same year, Kocabaş et al (35) also carried out another case-control study, including 103 patients and 84 controls, demonstrating a similar result to Bergman et al (32); however, no significant difference about the risk of allele T and C was observed. Furthermore, the majority of other publications suggested that the SOD2 Val-16Ala could not increase or decrease breast cancer risk and survival (26)(27)(28)(29)(30)(31)33,34,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50).…”

Antioxidant Enzymes as New Biomarkers for Prediction of Tumor Progression in Breast Cancer

“…The human MnSOD Ala variant has been found to generate 30-40% more active MnSOD protein compared to the Val variant in mitochondria (Sutton et al, 2003). The MnSOD Val/Val genotype having a low MnSOD activity as consequence could be considered as deleterious for mammary epithelial cells exposed to environmental carcinogens such as alcohol, tobacco smoke or estrogens generating O 2 •− during their metabolism (Bica et al, 2009). However, several epidemiologic studies have looked at the association between a MnSOD gene polymorphism and breast cancer risk.…”