title: Genetic variations in TERT-CLPTM1L locus are associated with risk of lung cancer in Chinese population.
abstract: 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 (Pinteraction = 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.
authors.affiliation: Department of Epidemiology and Biostatistics and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.forename: Rui
authors.initials: R
authors.lastname: Rui
authors.forename: Lu
authors.initials: L
authors.lastname: Long
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.forename: Xuzai
authors.initials: X
authors.lastname: Lu
authors.forename: Ti
authors.initials: T
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Wang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology; D000368:Aged; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000209:etiology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000453:epidemiology / Q000209:etiology*; D019098:Telomerase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: TERT-CLPTM1L; genetic variation; lung cancer