Polymorphisms in the DNA repair gene ERCC2/XPD and breast cancer risk: a HapMap-based case-control study among Han Women in a Chinese less-developed area

Abstract

Aims: Genetic variations in DNA repair genes may impact repair functions, DNA damage, and breast cancer risk. This study is aimed to assess the associations of genetic polymorphisms in excision repair cross-complementing group 2 (ERCC2) with the risk of developing breast cancer.

Materials and methods: In total, 101 histopathologically confirmed breast cancer cases and 101 age/region-matched healthy controls were genotyped for rs 3916840, rs 1799793, and rs 238416 in ERCC2 by polymerase chain reaction-restriction fragment length polymorphism.

Results: The rs 238416 heterozygous GA genotype combined with the rs 238416 genotypes (GA+AA) showed a significant association with breast cancer susceptibility (corrected p<0.01, odds ratio [OR]=0.29, 95% confidence interval [CI]=0.15-0.54; corrected p<0.01, OR=0.31, 95% CI=0.17-0.56, respectively). The rs 238416 GA genotype carriers had a decreased risk of breast cancer. However, we observed no significant association between the rs 3916840 and rs 1799793 polymorphisms in ERCC2 and breast cancer risk. Moreover, haplotype analysis showed that the ACG haplotype was associated with a significantly decreased risk of breast cancer, whereas the GCG haplotype was associated with a significantly increased risk of breast cancer (corrected p=0.004 and p=0.002, respectively). Multifactor dimensionality reduction analysis demonstrated that the interactions between rs 3916840 and rs 238416 were significantly synergistic.

Conclusion: To the best of our knowledge, this study is the first to demonstrate that the rs 238416 heterozygous genotype likely has a higher DNA repair capacity and, thus, can be protective against breast cancer in Chinese Han women.

FIG. 1.

Single nucleotide polymorphism (SNP)–SNP interaction model. The model describes the percent of entropy explanation by interactions to support interpretation of the relationship among SNPs. The boxes describe the SNPs with the percentage of entropy explained. Interaction is represented by lines. Interaction model is constructed on cases versus controls.