Genetic variants in GTF2H1 and risk of lung cancer: a case-control analysis in a Chinese population.
GTF2H1, the p62 subunit of the multiprotein complex transcription factor IIH (TFIIH), participates in both the nucleotide excision repair process and transcription control by specifically interacting with a variety of factors important in carcinogenesis. To elucidate the role of genetic variation in GTF2H1 in the etiology of lung cancer, we conducted a case-control study of 500 incident lung cancer cases and 517 controls in a Chinese population by genotyping six common single nucleotide polymorphisms (SNPs) in GTF2H1. An increased risk was associated with the variant genotypes of rs3802967 [adjusted odds ratio (OR)=1.38, 95% confidence interval (CI)=1.04-1.82], rs4150606 (adjusted OR=1.44, 95% CI=1.08-1.92), and rs4150678 (adjusted OR=1.37, 95% CI=1.04-1.81) in a dominant genetic model. The risk for rs3802967C/T+T/T genotypes was more pronounced among males subjects (P=0.002). In contrast, a decreased risk was associated with the rs4150667T/T genotype (adjusted OR=0.59, 95% CI=0.38-0.93) in a recessive model. Haplotype analysis showed that the haplotype "222212" (1 for common alleles and 2 for minor alleles) was associated with increased risk of lung cancer (P=0.03). Further evaluation using luciferase reporter constructs showed that the T allele of rs3802967 had higher luciferase expression, suggesting that the -79C-->T change may affect transcriptional activation of GTF2H1. Taken together, these results suggest that GTF2H1 polymorphisms/haplotypes may contribute to genetic susceptibility to lung cancer.
Wu
Wenting
W
The State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Liu
Hongliang
H
Lei
Rong
R
Chen
Dan
D
Zhang
Shuyu
S
Lv
Juan
J
Wang
Yi
Y
Fan
Weiwei
W
Qian
Ji
J
Jin
Guangfu
G
Ma
Hongxia
H
Miao
Ruifen
R
Hu
Zhibin
Z
Wang
Haifeng
H
Jin
Li
L
Wei
Qingyi
Q
Shen
Hongbing
H
Huang
Wei
W
Lu
Daru
D
D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000235:genetics*
C072546:GTF2H1 protein, human; D010750:Phosphoproteins; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH