Base excision repair genes XRCC1 and APEX1 and the risk for prostate cancer

Abstract

Prostate cancer is the second cause of cancer death in Brazilian men. One of the relevant phenomena to the inherited susceptibility is the presence of allelic variants in genes involved with the DNA repair pathway. The aim of this study was to analyze the frequencies of prevalent, heterozygous and rare genotypes of the base excision repair genes APEX1 and XRCC1 in a case-control study and relate the genotypes with tumoral aggressiveness. DNA from peripheral blood of 172 patients and 172 controls were analyzed by RFLP-PCR method. The polymorphisms were also evaluated in relation to clinical and pathological parameters. The OR (Odds Ratio) and confidence interval (CI = 95%) were used in the association study and the Chi-square and ANOVA tests for the evaluation of histopathological parameters. The rare genotypes frequencies of the gene APEX1 increased the risk for the development of prostate cancer (OR = 1.68 95% CI 1.10-2.58). No association was found for the gene XRCC1 (OR = 0.82 95% CI 0.53-1.27). The combined analysis for both genes did not show association with this neoplasia (OR = 1.27 95% CI 0.79-20.5). The relationship of XRCC1 and APEX1 genotypes with cancer aggressiveness through the correlation with histopathological parameters, did not find any association. Our results suggest that the polymorphism in the gene APEX1 may be indicated as a potential marker for prostate cancer risk.

Association between APE1 T1349G polymorphism and prostate cancer risk: evidence from a meta-analysis

“…A number of polymorphisms in common genes have been demonstrated to be associated with risk of prostate cancer [5,6]. Base excision repair (BER) pathway is one of the most important ways for the repair of DNA damage caused by oxidative reagents and alkylation [7][8][9][10]. Apurinic/apyrimidic endonuclease (APE1) is one of the key enzymes in the BER pathway [7][8][9][10].…”

“…Base excision repair (BER) pathway is one of the most important ways for the repair of DNA damage caused by oxidative reagents and alkylation [7][8][9][10]. Apurinic/apyrimidic endonuclease (APE1) is one of the key enzymes in the BER pathway [7][8][9][10]. APE1 can recognize and cleave the phosphodiester bond on the 5′-side to abasic sites, and then leave 5′-deoxyribose phosphate terminus for DNA repair synthesis [11,12].…”

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

“…16 So far, many studies have focused on the associations between PCa risk and DNA repair pathway gene polymorphisms. However, the results of these studies [6][7][8][17][18][19][20][21][22][23][24][25] are conflicting and inconclusive. Therefore, it is highly necessary to perform a quantitative and systematic study with rigorous methods.…”

Relationship between multidrug resistance 1 polymorphisms and the risk of prostate cancer in Chinese populations

“…The pathogenesis of Pca is still largely unknown, with genetic and environmental factors likely contributing to increased risk of the disease (Pienta and Esper 1993;Lichtenstein et al, 2000;Schaid, 2004). Several candidate genes have been suggested to be associated with Pca, including multidrug resistance 1 (MDR1) (van Brussel and Mickisch, 2003;Sanchez et al, 2009;Sanchez et al, 2011), X-ray repair complementing group 1 (Hirata et al, 2007;Agalliu et al, 2010;Dhillon et al, 2011;Kuasne et al, 2011;Langsenlehner et al, 2011), xeroderma pigmentosum group D gene (Mandal et al, 2010), APEX nuclease 1 gene (Agalliu et al, 2010;Kuasne et al, 2011;Mittal et al, 2012), Toll-like receptor 4 (Jing et al, 2012), axis inhibition protein 2 (Pinarbasi et al, 2011), 2-5A-dependent RNase (Wei et al, 2012), complementation group G gene (Berhane et al, 2012), and N-acetyltransferase types 1 (Gong et al, 2011) and 2 (Gong et al, 2011;de Lima Junior et al, 2012). MDR1 is an important candidate gene for Pca.…”