title: TERT rs2736100T/G polymorphism upregulates interleukin 6 expression in non-small cell lung cancer especially in adenocarcinoma.
abstract: Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase, especially the rate-limiting determinant of telomerase activity. Accumulating evidence has suggested that TERT could modulate the expression of numerous genes including interleukin 6 (IL-6), an important cytokine for the development of lung cancer. It has been reported that TERT polymorphism rs2736100T/G is associated with increased susceptibility to non-small cell lung cancer (NSCLC). However, the mechanism remains unclear. In the current study, we investigated the association between rs2736100T/G and NSCLC in 1,552 NSCLC and 1,602 healthy controls. Data revealed that the prevalence of TG and GG genotypes were significantly elevated in patients than in controls (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.01-1.39; p = 0.040 and OR = 1.46; 95% CI, 1.19-1.78; p < 0.001, respectively). The association was more prominent in patients with lung adenocarcinoma than those with squamous cell carcinoma (p = 0.039). When analyzing the function of the polymorphism, we observed a significantly augmented level of IL-6 in subjects with GG genotype than those with GT and TT genotypes. Interestingly, the upregulation of IL-6 by GG genotype was 2.3-fold higher in lung adenocarcinoma compared to squamous cell carcinoma. These results suggest that the rs2736100T/G polymorphism modulates IL-6 expression and may play a unique role in lung adenocarcinoma.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Fuxia
authors.initials: F
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.forename: Yixin
authors.initials: Y
authors.lastname: Pang
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Liu
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Shao
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Ti
authors.initials: T
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C509186:TERT protein, human; D019098:Telomerase