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Genetic variations in TERT ‐ CLPTM 1 L locus are associated with risk of lung cancer in chinese population
Author(s) -
Zhong Rong,
Liu Li,
Zou Li,
Zhu Yaowu,
Chen Wei,
Zhu Beibei,
Shen Na,
Rui Rui,
Long Lu,
Ke Juntao,
Lu Xuzai,
Zhang Ti,
Zhang Yu,
Wang Zhenling,
Liu Lifeng,
Sun Yu,
Cheng Liming,
Miao Xiaoping
Publication year - 2013
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22043
Subject(s) - biology , lung cancer , genome wide association study , haplotype , single nucleotide polymorphism , locus (genetics) , allele , genetics , population , lung cancer susceptibility , bonferroni correction , oncology , genetic association , logistic regression , genotype , adenocarcinoma , medicine , cancer , gene , demography , sociology , statistics , mathematics
Recent genome‐wide association studies (GWAS) have reported multiple genetic variations at 5p15.33 ( TERT‐CLPTM1L ) associated with risk of lung cancer. However, most of the associated variations identified by GWAS thus far are unlikely to be the actual causal variants, but may be mostly marker‐single nucleotide polymorphisms tagging functional variations that influence gene expression. This study aimed to explore the function‐validated and potentially functional variations in TERT‐CLPTM1L locus conferring susceptibility to lung cancer. A case–control study including 502 cases and 502 controls in Chinese Han population was firstly conducted. Bioinformatic approaches are applied to prioritize genetic variations based on their potential functionality. In the logistic regression analysis, TERT ‐rs2853669, rs2736108, and CLPTM1L ‐rs31490 were significant associated with increased risk of lung cancer (OR = 1.46, 95% CI = 1.22–1.75; OR = 1.22, 95% CI = 1.00–1.49 and OR = 1.74, 95% CI = 1.35–2.23 under additive model, respectively). The significant associations were observed in non‐small‐cell lung cancer but not‐in‐small‐cell lung cancer, and more prominent in adenocarcinoma. Haplotype analysis presented a significant allele‐dose effect of haplotypes in increasing risk of lung cancer ( P for trend = 1.894 × 10 −6 ). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of TERT ‐rs2853669, rs2736108, and CLPTM1L ‐rs31490, even after bonferroni correction for multiple comparisons ( P interaction = 1.316 × 10 −9 , 3.912 × 10 −4 , and 2.483 × 10 −5 , respectively). These findings indicated that the function‐validated and potentially functional variations in TERT‐CLPTM1L locus, modified by smoking, may play a substantial role in the susceptibility to lung cancer. © 2013 Wiley Periodicals, Inc.