Genetic Variations in TERT-CLPTM1L Locus Are Associated With Risk of Lung Cancer in Chinese Population

被引：38

作者：

Zhong, Rong ^{[1
,2
]}

Liu, Li ^{[3
,4
]}

Zou, Li ^{[1
,2
]}

Zhu, Yaowu ^{[5
]}

Chen, Wei ^{[1
,2
]}

Zhu, Beibei ^{[1
,2
]}

Shen, Na ^{[1
,2
]}

Rui, Rui ^{[1
,2
]}

Long, Lu ^{[1
,2
]}

Ke, Juntao ^{[1
,2
]}

Lu, Xuzai ^{[1
,2
]}

Zhang, Ti ^{[1
,2
]}

Zhang, Yu ^{[1
,2
]}

Wang, Zhenling ^{[1
,2
]}

Liu, Lifeng ^{[1
,2
]}

Sun, Yu ^{[1
,2
]}

Cheng, Liming ^{[5
]}

Miao, Xiaoping ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Sch Publ Hlth, Dept Epidemiol & Biostat, Tongji Med Coll, Wuhan 430030, Peoples R China

[2] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, Minist Educ,Key Lab Environm & Hlth, Wuhan 430030, Peoples R China

[3] Guangdong Pharmaceut Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Guangzhou, Guangdong, Peoples R China

[4] Guangdong Pharmaceut Univ, Sch Publ Hlth, Guangdong Key Lab Mol Epidemiol, Guangzhou, Guangdong, Peoples R China

[5] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Lab Med, Tongji Med Coll, Wuhan 430030, Peoples R China

来源：

MOLECULAR CARCINOGENESIS | 2013年 / 52卷

关键词：

genetic variation; TERT-CLPTM1L; lung cancer; GENOME-WIDE ASSOCIATION; FUNCTIONAL POLYMORPHISM; TELOMERE DYSFUNCTION; SUSCEPTIBILITY LOCI; EXPRESSION; PROMOTER; VARIANTS; SMOKING; TOBACCO; TERT;

D O I：

10.1002/mc.22043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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=1.894x10(-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=1.316x10(-9), 3.912x10(-4), and 2.483x10(-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. (c) 2013 Wiley Periodicals, Inc.

引用

页码：118 / 126

页数：9

共 45 条

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