Interethnic variability of ERCC2 polymorphisms

Abstract

Excision Repair Cross-Complementing Rodent Repair Group 2 (ERCC2) plays an important role in DNA repair by eliminating bulky DNA adducts produced by platinum agents during the nucleotide excision repair pathway. Several studies have associated polymorphisms in ERCC2 with response to platinum therapy, lung cancer risk, and DNA repair capacity. This study examined ERCC2 polymorphisms and haplotype structure across 18.9 kb in 95 European, 95 African, and 95 Asian individuals. Single-nucleotide polymorphisms (SNPs) (ERCC2 À9164 A4T, À1989 A4G, À516 G4A, 468, and 2251 T4G [Lys751Gln]) were mined and mapped using Golden Path, PolyMAPr, and Promolign. Genotyping was performed using PCR and pyrosequencing. Allele frequencies ranged from 0 to 0.47 (Europeans), 0.05 to 0.72 (Africans), and 0 to 0.47 (Asians). The synonymous cSNP at codon 579 could not be confirmed in our populations. There were significant differences in haplotype structure and frequency between populations. This information on ERCC2 genomic structure will allow the construction of definitive studies to clarify the clinical role of this important gene.

DNA repair gene polymorphisms in the nucleotide excision repair pathway and lung cancer risk: A meta-analysis

“…However, the haplotype structure and frequency between populations were significant different in European, African and Asian individuals. In both the African and Asian populations, C156A was not significantly linked to A751C [73] . In our meta-analysis, the 156A allele frequency was varied from0.441 to 0.459 in Asian and very different from African Americans (0.136).…”

The Polymorphism of DNA Repair Gene ERCC2/XPD Arg156Arg and Susceptibility to Breast Cancer in a Chinese Population

“…In our previous research on a Chinese lung cancer study group (Yin et al 2006), ERCC2 Lys751Gln and Arg156Arg were at incomplete linkage disequilibrium at a relatively lower level (D 0 = 0.355). A study (King et al 2005) found that ERCC2 codon 156 was linked to codon 751 in a European population, but not in African and Asian populations (D 0 values were not significant). Their findings agree with ours.…”

Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer

“…The linkage between Lys751Gln and Asp312Asn was r 2 = 0.56 in populations of European ancestry and r 2 = 0.11 in populations of African ancestry [19]. Therefore, linkage disequilibrium differences among these populations may also impact on the outcomes of these polymorphisms [60].…”