ERCC6/CSB gene polymorphisms and lung cancer risk.
Nucleotide excision repair (NER) enzymes are critical for the removal of bulky DNA adducts caused by environmental carcinogens such as smoking. Of them, Cockayne syndrome complementation group B (CSB), coded by ERCC6, recruits NER repair factors to the DNA damage site and plays an important role in the repair process. Genetic variants of ERCC6 may alter the regulation of DNA repair and therefore were hypothesized to be associated with altered risk of smoking-related lung cancer. To test this hypothesis, we genotyped eight tagging single nucleotide polymorphisms (tSNPs) and three potentially functional SNPs of ERCC6 in 500 incident lung cancer cases and 517 controls in a Chinese population. Single locus analyses showed that none of the single SNP alone had the significant main affect on the risk of lung cancer. However, the combined variant genotypes of the four loci with P(trend) approaching to 0.10 (rs2228526, rs4253160, rs12571445 and rs3793784) were associated with a significantly increased lung cancer risk (adjusted OR 1.35, 95% CI, 1.04-1.75 among subjects carrying three or more variant alleles), indicating that multiple loci in ERCC6 may jointly contribute to the susceptibility of lung cancer. These findings, if validated, may contribute to identify at-risk subjects in the general population for smoking-related lung cancer.
Ma
Hongxia
H
Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, School of Public Health, 140 Han-Zhong Road, Nanjing, Jiangsu 210029, China.
Hu
Zhibin
Z
Wang
Haifeng
H
Jin
Guangfu
G
Wang
Ying
Y
Sun
Weiwei
W
Chen
Dan
D
Tian
Tian
T
Jin
Li
L
Wei
Qingyi
Q
Lu
Daru
D
Huang
Wei
W
Shen
Hongbing
H
D002681:China / Q000453:epidemiology; D004265:DNA Helicases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes