**10. Common polymorphisms in redox enzymes are associated with ovarian cancer**

A single nucleotide polymorphism (SNP) occurs as a result of gene point mutations with an estimated frequency of at least one in every 1000 base pairs that are selectively maintained and distributed in populations throughout the human genome [132]. An association between common SNPs in oxidative DNA repair genes and redox genes with human cancer susceptibility has been established [28]. Common SNPs in the redox enzymes are known to be strongly associated with an altered enzymatic activity in these enzymes, and may explain the enhanced redox state that has been linked to several malignancies, including ovarian cancer [40, 52]. Additionally, it may further explain the observation of significantly decreased apoptosis and increased survival of EOC cells [53]. It is therefore critical to determine the exact effect of common SNPs in various redox enzymes on all process involved in the development of the oncogenic phenotype [21, 46, 133, 134]. Such studies can be linked to other studies focusing on determining the effects of genes involved in carcinogen metabolism (detoxification and/or activation), redox enzymes, and DNA repair pathways [133]. Numerous SNPs associated with change of function have been identified in antioxidant enzymes including *CAT*, *GPX1*, *GSR*, and *SOD2* [21, 134]. Additionally, the association between genetic polymorphisms in genes with anti-tumor activity and those involved in the cell cycle has been reported in ovarian cancer [135, 136]. Recently, several genetic variations have been identified in genome-wide association studies (GWAS), and were found to act as low to moderate penetrant alleles, which contribute to ovarian cancer risk, as well as other diseases [23, 137].

There is now an association of specific SNPs in key oxidant and anti-oxidant enzymes with increased risk and overall survival of ovarian cancer [21, 46]. A common SNP that reduced CAT activity (rs1001179) was utilized as a significant predictor of death when present in ovarian cancer patients and was also associated with increased risk for breast cancer [21, 46, 134, 138]. This SNP is also linked to increased risk, survival, and response to adjuvant treatment of cancer patients, including ovarian [46, 139]. Another common SNP that reduced CYBA activity (rs4673) was also reported to be associated with an increased risk for ovarian cancer [21, 46]. The mutant genotype of the *CYBA* gene has been shown to both decrease and increase activity of the protein, thereby altering the generation of O2 ●– [21, 46]. Moreover, functionally distinct *MPO* polymorphisms, such as (rs2333227) have been linked to relative increased risk for development of ovarian cancer as well as other cancers [21, 44, 46]. Additional SNPs that influenced the risk of EOC have been successfully identified from the GWAS studies including rs3814113 (located at 9p22, near BNC2), rs2072590 (located at 2q31, which contains a family of HOX genes), rs2665390 (located at 3q25, intronic to TIPARP), rs10088218 (located at 8q24, 700 kb downstream of MYC), rs8170 (located at 19p13, near MERIT40), and rs9303542 (located at 17q21, intronic to SKAP1) [21, 46]. Thus, the genetic component of increased ovarian cancer risk may be attributed to SNPs that result in point mutations in the redox genes and potentially other genes [140].
