TY - JOUR
T1 - XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity
AU - Wu, Xifeng
AU - Zhao, Hua
AU - Wei, Qingyi
AU - Amos, Christopher I.
AU - Zhang, Kerang
AU - Guo, Zhaozheng
AU - Qiao, Yawei
AU - Hong, Waun K.
AU - Spitz, Margaret R.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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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U2 - 10.1093/carcin/24.3.505
DO - 10.1093/carcin/24.3.505
M3 - Article
C2 - 12663511
AN - SCOPUS:0037356919
SN - 0143-3334
VL - 24
SP - 505
EP - 509
JO - Carcinogenesis
JF - Carcinogenesis
IS - 3
ER -