Genetic variants in GTF2H1 and risk of lung cancer: A case–control analysis in a Chinese population

SummaryGTF2H1, 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 rs3802967 C/T + T/T genotypes was more pronounced among males subjects (P = 0.002). In contrast, a decreased risk was associated with the rs4150667 T/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.