Open AccessIdentification of a functional variant for colorectal cancer risk mapping to chromosome 5q31.1
Author(s) -
Juntao Ke,
Jiao Lou,
Xueqin Chen,
Jiaoyuan Li,
Cheng Liu,
Yajie Gong,
Yang Yang,
Ying Zhu,
Yi Zhang,
Jianbo Tian,
Jiang Chang,
Rong Zhong,
Jing Gong
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.9298
Subject(s) - expression quantitative trait loci , single nucleotide polymorphism , colorectal cancer , genetics , genome wide association study , locus (genetics) , allele , quantitative trait locus , biology , genetic association , snp , gene , genotype , oncology , medicine , cancer
Genome-wide association studies (GWASs) have established chromosome 5q31.1 as a risk locus for colorectal cancer (CRC). We previously identified a potentially regulatory single nucleotide polymorphism (SNP) rs17716310 within 5q31.1. Now, we extended our study with another independent Chinese population, functional assays and analyses of TCGA (The Cancer Genome Atlas) data. Significant associations between rs17716310 and CRC risk were found in Present Study including 1075 CRC cases and 1999 controls (additive model: OR = 1.149, 95% CI = 1.027-1.286, P = 0.016), and in Combined Study including 1766 cases and 2708 controls (additive model: OR = 1.145, 95% CI = 1.045-1.254, P = 0.004). Dual luciferase reporter gene assays indicated that the variant C allele obviously increased transcriptional activity. Using TCGA datasets, we indicated rs17716310 as a cis expression quantitative trait locus (eQTL) for the gene SMAD5, whose expression was significantly higher in CRC tissues. These findings suggested that the functional polymorphism rs17716310 A > C might be a genetic modifier for CRC, promoting the expression of SMAD5 that belonged to the transforming growth factor beta (TGF-β) signaling pathway.