Author:
Shi Qiang,Ruan Ji,Yang Yu-Chen,Shi Xiao-Qian,Liu Shao-Dong,Wang Hong-Yan,Zhang Shi-Jiao,Wang Si-Qi,Zhong Li,Sun Chang
Abstract
Lung cancer is a malignant tumor with high rates of mortality and shows significant hereditary predisposition. Previous genome-wide association studies suggest that rs748404, located at promoter of TGM5 (transglutaminase 5), is associated with lung carcinoma. By analysis of 1000 genomes project data for three representative populations in the world, another five SNPs are identified to be in strong linkage disequilibrium with rs748404, thus suggesting that they may also be associated with lung carcinoma risk. However, it is ambiguous about the actually causal SNP(s) and the mechanism for the association. Dual-luciferase assay indicates that the functional SNPs are not rs748404, rs12911132 or rs35535629 but another three SNPs (rs66651343, rs12909095 and rs17779494) in lung cell. By chromosome conformation capture, it is disclosed that the enhancer encompassing the two SNPs, rs66651343 and rs12909095, can interact with the promoter of CCNDBP1 (cyclin D1 binding protein 1). RNA-seq data analysis indicates that CCNDBP1 expression is dependent on the genotype of these two SNPs. Chromatin immunoprecipitation assay suggests that the fragments spanning rs66651343 and rs12909095 can bind with the transcription factors, cut like homeobox 1 and SRY-box transcription factor 9, respectively. Our results establish the connection between genetic variations at this locus and lung cancer susceptibility.
Funder
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
Publisher
Public Library of Science (PLoS)
Reference45 articles.
1. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries;H Sung;CA Cancer J Clin,2021
2. Genetic susceptibility to lung cancer and co-morbidities;IA Yang;J Thorac Dis,2013
3. Lung health, tobacco, and related products: gaps, challenges, new threats, and suggested research;S St Claire;Am J Physiol Lung Cell Mol Physiol,2020
4. Short-term association between ambient air pollution and lung cancer mortality;N Wang;Environ Res,2019
5. Asbestos, Smoking and Lung Cancer: An Update;S Klebe;Int J Environ Res Public Health,2019