1. ¹Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA
2. ²Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA

Correspondence: Dr S Marsh, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO 63110, USA. Tel: +314 747 5184; Fax: +314 362 3764; E-mail: smarsh@im.wustl.edu

Received 26 April 2004; Revised 25 August 2004; Accepted 6 September 2004; Published online 9 November 2004.

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 -9164 A>T, -1989 A>G, -516 G>A, 468 C>A [Arg156Arg], 1737 C>T [Val579Val], 2133 C>T [Asp711Asp], and 2251 T>G [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.