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POLYMORPHISMS IN THE DNA NUCLEOTIDE EXCISION REPAIR GENES AND LUNG CANCER RISK IN XUAN WEI, CHINA
Citation:
Shen, M., N. Rothman, S. I. Berndt, M. R. Bonner, M. Yeager, R. Welch, S. Chanock, N. Caporaso, Q. Lan, D. M. DEMARINI, J. S. MUMFORD, X. HE, L. TIAN, AND T. ZHENG. POLYMORPHISMS IN THE DNA NUCLEOTIDE EXCISION REPAIR GENES AND LUNG CANCER RISK IN XUAN WEI, CHINA. International Journal of Cancer. John Wiley & Sons, Ltd., Indianapolis, IN, 116:768-773, (2005).
Impact/Purpose:
The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country. we found that genetic variants in genes involved in NER pathway may play a role on lung cancer susceptibility in Xuan Wei, which is consistent with the point that environmental exposure to PAHs is an important risk factor for lung cancer.
Description:
The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country and has been etiologically attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) in six genes involved in NER in a population-based case-control study in Xuan Wei. A total of 122 incident primary lung cancer cases were enrolled with 122 individually matched controls. Analysis was carried out for each SNP and estimated haplotypes of each gene using unconditional logistic regression. Three tightly linked SNPs in ERCC2 were associated with lung cancer with similar odds ratios, e.g., persons with Gln allele at codon 751 had a 60% reduction of lung cancer risk (OR, 0.40; 95% CI, 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR, 0.40; 95% CI, 0.19-0.84) compared with the most common haplotype. In addition, subjects with one or two copies of Val allele at codon 249 of RAD23B had a two-fold risk of lung cancer (OR, 1.91; 95% CI, 1.12-3.24). In summary, we found that genetic variants in genes involved in NER pathway may play a role on lung cancer susceptibility in Xuan Wei, which is consistent with the point that environmental exposure to PAHs is an important risk factor for lung cancer.
