Journal
CARCINOGENESIS
Volume 24, Issue 3, Pages 505-509Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/24.3.505
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Funding
- NCI NIH HHS [P01 CA52051, U19 CA68437] Funding Source: Medline
- PHS HHS [R01 55769] Funding Source: Medline
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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.
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