DNA repair genes XRCC1 and XRCC3 polymorphisms and their relationship with the level of micronuclei in breast cancer patients

Abstract

Breast cancer (BC) is the most prevalent type worldwide, besides being one of the most common causes of death among women. It has been suggested that sporadic BC is most likely caused by low-penetrance genes, including those involved in DNA repair mechanisms. Furthermore, the accumulation of DNA damage may contribute to breast carcinogenesis. In the present study, the relationship between two DNA repair genes, viz., XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms, and the levels of chromosome damage detected in 65 untreated BC women and 85 healthy controls, was investigated. Chromosome damage was evaluated through micronucleus assaying, and genotypes determined by PCR-RFLP methodology. The results showed no alteration in the risk of BC and DNA damage brought about by either XRCC1 (Arg399Gln) or XRCC3 (Thr241Met) action in either of the two groups. Nevertheless, on evaluating BC risk in women presenting levels of chromosome damage above the mean, the XRCC3Thr241Met polymorphism was found to be more frequent in the BC group than in the control, thereby leading to the conclusion that there is a slight association between XRCC3 (241 C/T) genotypes and BC risk in the subgroups with higher levels of chromosome damage.

XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta-analysis Study

“…Through a detailed search of databases, 53 literatures were identified for further evaluation (Figure 1) (Kim et al, 2002b;Han et al, 2003;Moullan et al, 2003;Shu et al, 2003;Smith et al, 2003a;Smith et al, 2003b;Deligezer and Dalay, 2004;Figueiredo et al, 2004;Försti et al, 2004;Huang et al, 2004;Chacko et al, 2005;Dufloth et al, 2005;Metsola et al, 2005;Patel et al, 2005b;Shen et al, 2005;Brewster et al, 2006;Bu et al, 2006;Pachkowski et al, 2006b;Thyagarajan et al, 2006;Zhai et al, 2006;Zhang et al, 2006b;Costa et al, 2007;Silva et al, 2007b;Ali et al, 2008;Kipikasova et al, 2008;Loizidou et al, 2008;Mitra et al, 2008;Saadat et al, 2008;Sangrajrang et al, 2008;Smith et al, 2008;Sobczuk et al, 2009a;Syamala et al, 2009;Jakubowska XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta- , 2010;Jelonek et al, 2010;Ming-Shiean et al, 2010;Romanowicz et al, 2010;Santos et al, 2010;…”

Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of 36 Case-control Studies

“…A total of 26 articles involving 36 eligible studies with 23, 812 cases and 25, 349 controls were included in the pooled analyses (Jacobsen et al, 2003;Smith et al, 2003a;2003b;Figueiredo et al, 2004;Forsti et al, 2004;Han et al, 2004;Dufloth et al, 2005;Millikan et al, 2005;Webb et al, 2005;Zhang et al, 2005;Thyagarajan et al, 2006;Breast Cancer Association, 2006;Garcia-Closas et al, 2006;Costa et al, 2007;Sangrajrang et al, 2007;Lee et al, 2007;Loizidou et al, 2008;Smith et al, 2008;Brooks et al, 2008;Krupa et al, 2009;Jara et al, 2010;Santos et al, 2010;Silva et al, 2010;Sterpone et al, 2010;Romanowicz-Makowska et al, 2011;RomanowiczMakowska et al, 2012). Out of the 100 abstracts retrieved through the search criteria, fifty-four were irrelevant, nine articles were excluded because they were conducted on other XRCC3 polymorphisms.…”

Individual capacity for detoxification of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair

“…XRCC3 Thr241Met polymorphism is weakly associated with risk for breast cancer [143]. may be associated with predisposi on to aplas c anemia and acute lymphoblas c leukemia [144,145].…”