TY - JOUR
T1 - Interethnic variability of ERCC2 polymorphisms
AU - King, C. R.
AU - Yu, J.
AU - Freimuth, R. R.
AU - McLeod, H. L.
AU - Marsh, S.
N1 - Funding Information:
This work was supported by the NIH Pharmacogenetics Research Network (GM63340; http://pharmacogenetics.wustl.edu) and the Site-man Cancer Center (P30CA091842). These data have been deposited in the Pharmacogenetics Knowledge Base (http://www.pharmgkb.org/).
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - ERCC2
KW - Pharmacogenetics
KW - Polymorphism
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U2 - 10.1038/sj.tpj.6500283
DO - 10.1038/sj.tpj.6500283
M3 - Article
C2 - 15534626
AN - SCOPUS:13544255725
SN - 1470-269X
VL - 5
SP - 54
EP - 59
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 1
ER -