Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk

Abstract

Genetic variations in DNA repair may impact repair functions, DNA damage and breast cancer risk. Using data/samples collected from the first 752 Caucasians and 141 African-Americans in an ongoing case-control study, we examined the association between breast cancer risk and 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways-(i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) double-strand break repair: NBS1 E185Q and XRCC3 T241M. In Caucasians, breast cancer risk was significantly associated with ADPRT 762VV [odds ratio (OR) = 1.45; 95% confidence interval (CI) = 1.03, 2.03], APE1 148DD (OR = 1.44; 95% CI = 1.03, 2.00), MLH1 219II/IV (OR = 1.87; 95% CI = 1.11, 3.16) and ERCC4 415QQ (OR = 8.64; 95% CI = 1.04, 72.02) genotypes. With a limited sample size, we did not observe any significant association in African-Americans. However, there were significant trends in breast cancer risk with increasing numbers of risk genotypes for ADPRT 762VV, APE1 148DD, ERCC4 415RQ/QQ and MLH1 219II/IV (P(trend) < 0.001) in Caucasians and ADPRT 762VA, ERCC2 751KQ/QQ and NBS1 185EQ/QQ in African-Americans (P(trend) = 0.006), respectively. Our results suggest that combined nsSNPs in multiple DNA repair pathways may contribute to breast cancer risk and larger studies are warranted to further evaluate polygenic models of DNA repair in breast cancer risk.

Xeroderma pigmentosum complementation group C single‐nucleotide polymorphisms in the nucleotide excision repair pathway correlate with prolonged progression‐free survival in advanced ovarian cancer

“…Polymorphisms of XPF have been associated with cancers of the bladder, pancreas, and breast. [25][26][27] Although reports on several common XPF SNPs have been published previously, these did not share a relation with the significant XPF SNP (rs12926685) that was identified in our current study. Two SNPs in the ERCC1 gene (rs11615 and rs3212986) have been correlated with platinum response in ovarian cancer in recently published studies, although the results were discrepant.…”

XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis

“…Out of the 55 abstracts retrieved through the search criteria, 25 were irrelevant, four articles [8][9][10][11] were excluded because they were conducted on overlapping populations with other eligible studies [2,3,5,12] (these excluded articles represent smaller studies performed on subsets of larger eligible studies), one study [13] was excluded given that it has not included controls in its study design, three articles [4,14,15] were reviews/meta-analyses, and three studies [16][17][18] were excluded due to other reasons (two of them [16,17] were excluded due to reporting reasons, i.e. no reporting of the relevant genotype frequencies, whereas the other [18] was excluded for examining the association between other XRCC3 polymorphisms and premenopausal breast cancer risk).…”

“…no reporting of the relevant genotype frequencies, whereas the other [18] was excluded for examining the association between other XRCC3 polymorphisms and premenopausal breast cancer risk). As a result, 19 case-control articles [2,3,5,12,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]] (23 case-control studies, considering that Breast Cancer Association Consortium has more than one studies included) were included in this meta-analysis; 20 case-control studies on non-Chinese subjects (19,575 cases and 21,125 controls) and three case-control studies [3,24,29] on Chinese subjects (1,216 cases and 1,112 controls). Table 1 presents in detail the results of the meta-analysis.…”

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Four publications were excluded because of meta-analysis, control group had cancer patients or not published in English. Finally, 26 full-text articles with eligibility were included in this meta-analysis (Smith et al, 2003;Huang et al, 2006;Mechanic et al, 2006;Moreno et al, 2006;Crew et al, 2007;Jorgensen et al, 2007;Chang et al, 2008;Hung et al, 2008;McWilliams et al, 2008;Rajaraman et al, 2008;Abbasi et al, 2009;Han et al, 2009;Joshi et al, 2009;Agalliu et al, 2010;Rajaraman et al, 2010;Doherty et al, 2011;Krupa et al, 2011;Smith et al, 2011;Gil et al, 2012;Yu et al, 2012;Cheng et al, 2013;Santos et al, 2013;Wang et al, 2013;Wyss et al, 2013;Kohlhase et al, 2014;Steck et al, 2014). The flow chart which reflected the details of article selection was presented in Figure 1.…”