title: Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer.
abstract: The excision repair cross-complementing group 2 gene (ERCC2) plays a key role in DNA repair. Several polymorphisms in the ERCC2 gene have been described, including the commonly occurring Lys751Gln and Asp312Asn polymorphisms. Studies investigating the association of these polymorphisms with breast cancer risk produced controversial results. To evaluate these associations presented in diverse populations, we have conducted a meta-analysis based on 40 studies from 33 publications in PubMed which included analyses of Lys751Gln (14,545 cases, 15,352 controls) and Asp312Asn polymorphisms (16,254 cases, 14,006 controls). Overall findings of both polymorphisms have implicated null effects (OR = 1.01-1.03) when the analyses were limited to the statistically powerful (≥80%) studies. Although modestly increased statistically significant breast cancer risk was detected in the underpowered studies (≤80%), removal of outliers resulted in null associations. Ethnic stratification showed non-significant and relatively null associations for both polymorphisms with breast cancer risk for the overall Caucasians as well as North American and the European sub-populations. Although statistically increased and decreased risks were observed for the homogenous populations of African-Americans (Lys751Gln, OR 1.25, 95% CI 1.03-1.53, P = 0.03) and Asians (Asp312Asn, ORs: 0.53-0.55, P values: 0.02-0.03), respectively, this may be the result of small sample size. Analyses of the homogeneous adduct studies, with relatively large sample size, exhibited increased risk for Lys751Gln (OR 1.20, 95% CI (1.02-1.41), P = 0.03) and Asp312Asn (OR 1.17 95% CI 1.02-1.34, P = 0.03) under the dominant genetic model. In conclusion, our results suggest null associations of both polymorphisms in the overall and the Caucasian subgroups, although some effects can be suggested for relatively smaller minority studies. Increased risk effect was more visible when the adduct studies are considered, suggesting the role of these polymorphisms in the presence of exposure to DNA damaging agents.
authors.affiliation: College of Natural Sciences, Saint Louis University, Baguio City, 2600, Philippines.
authors.forename: Noel
authors.initials: N
authors.lastname: Pabalan
authors.forename: Ofelia
authors.initials: O
authors.lastname: Francisco-Pabalan
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.forename: Hamdi
authors.initials: H
authors.lastname: Jarjanazi
authors.forename: Hilmi
authors.initials: H
authors.lastname: Ozcelik
mesh_terms: D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human