title: 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 -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.
authors.affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: R R
authors.initials: RR
authors.lastname: Freimuth
authors.forename: H L
authors.initials: HL
authors.lastname: McLeod
authors.forename: S
authors.initials: S
authors.lastname: Marsh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D044469:Racial Groups / Q000208:ethnology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human