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Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer
Author(s) -
Ren Anjing,
Sun Shanwen,
Li Shuwei,
Chen Tao,
Shu Yongqian,
Du Mulong,
Zhu Lingjun
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32079
Subject(s) - colorectal cancer , genetics , medicine , biology , oncology , cancer , bioinformatics
Previous a genome‐wide association study (GWAS) of colorectal cancer in Japanese population has identified a risk region at the chromosome 6q26‐q27 associated with colorectal cancer risk. However, the causal gene at this locus remained unclear. In our study, we enrolled a total of 14 candidate functional single nucleotide polymorphisms (SNPs) at 6q26‐q27 (318 kb), and then genotyped them by TaqMan method in a Chinese population including 1,147 colorectal cancer cases and 1,203 controls. Among that, 5 SNPs were identified statistical association with colorectal cancer risk by logistic regression analysis. Of which, SNP rs420038 G > A in SLC22A3 was related to decreased risk of colorectal cancer (adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.67–0.94, p = 0.007), and also associated with lower expression of SLC22A3 ( p = 0.040) using expression quantitative trait loci (eQTL) analysis. Moreover, by the luciferase assays, we found that compared to the G allele of rs420038, the A allele could suppress the activity of the promoter in SLC22A3 . Furthermore, the expression of SLC22A3 was significantly higher in colorectal cancer tissues than that in paired normal tissues ( p < 0.001). Meanwhile, the phenotypes of proliferation, migration, invasion, cell cycle and apoptosis of colorectal cancer cell were significantly affected by SLC22A3 in vitro . Our results revealed a novel susceptible locus, rs420038 in SLC22A3 , which may be involved in colorectal cancer development and progression.