XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity.

Journal Article

XPA, a DNA binding protein in the nucleotide excision repair (NER) pathway, modulates damage recognition. Recently, a common single-nucleotide polymorphism (A --> G) of unknown function was identified in the 5' non-coding region of the XPA gene. Because a deficiency in NER is associated with an increased risk of lung cancer, we evaluated the role of this polymorphism in 695 lung cancer case patients and 695 age-, sex-, ethnicity- and smoking-matched control subjects. We also studied the effect of this polymorphism on NER capacity in a subset sample for whom the host cell reactivation data were available. The presence of one or two copies of the G allele was associated with a reduced lung cancer risk for Caucasians [adjusted odds ratio (ORadj) = 0.69 [95% confidence interval (CI) = 0.53-0.90]], Mexican-Americans [ORadj = 0.32 (95% CI = 0.12-0.83)] and African-Americans [ORadj = 0.45 (95% CI = 0.16-1.22)]. In Caucasians, ever smokers with one or more copies of the G allele were observed to have a significantly reduced risk of lung cancer. Control subjects with one or two copies of the G allele demonstrated more efficient DRC than did those with the homozygous A allele. Our data suggest that the XPA 5' non-coding region polymorphism modulates NER capacity and is associated with decreased lung cancer risk, especially in the presence of exposure to tobacco carcinogens.

Full Text

Duke Authors

Cited Authors

  • Wu, X; Zhao, H; Wei, Q; Amos, CI; Zhang, K; Guo, Z; Qiao, Y; Hong, WK; Spitz, MR

Published Date

  • March 2003

Published In

Volume / Issue

  • 24 / 3

Start / End Page

  • 505 - 509

PubMed ID

  • 12663511

Electronic International Standard Serial Number (EISSN)

  • 1460-2180

International Standard Serial Number (ISSN)

  • 0143-3334

Digital Object Identifier (DOI)

  • 10.1093/carcin/24.3.505

Language

  • eng