J Cancer 2020; 11(23):6841-6849. doi:10.7150/jca.47189

Research Paper

Genetic Fine Mapping and Genomic Annotation Defines Causal Mechanisms at A Novel Colorectal Cancer Susceptibility Locus in Han Chinese

Kewei Jiang3*, Fengying Du1*, Liang lv4, Hongqing Zhuo1,2, Tao Xu1,2, Lipan Peng1,2, Yuezhi Chen1,2, Leping Li1,2, Jizhun Zhang1,2✉

1. Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
2. Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
3. Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
4. Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
*Equal co-first authorship.

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Citation:
Jiang K, Du F, lv L, Zhuo H, Xu T, Peng L, Chen Y, Li L, Zhang J. Genetic Fine Mapping and Genomic Annotation Defines Causal Mechanisms at A Novel Colorectal Cancer Susceptibility Locus in Han Chinese. J Cancer 2020; 11(23):6841-6849. doi:10.7150/jca.47189. Available from http://www.jcancer.org/v11p6841.htm

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Abstract

Genome-wide association studies of colorectal cancer (CRC) have identified two risk SNPs. The characterization of these risk regions in diverse racial groups with different linkage disequilibrium structure would aid in localizing the causal variants. Herein, fine mapping of the established CRC loci was carried out in 1,508 cases and 1,482 controls obtained from the Han Chinese population. One distinct association signal was identified at these loci, where fine mapping implicated rs1010208 as a functional locus. Next, the candidate target genes of functional SNP rs1010208 were analyzed using data from TCGA databases by expression quantitative trait loci analysis method; the data from Peking University People's Hospital were utilized for verification. The dual-luciferase reporter system analysis confirmed that rs1010208 is a regulatory region that can be mutated to decrease the expression of HINT1, resulting in proliferation and invasiveness of CRC.

Keywords: genome-wide association study, fine mapping, colorectal cancer, susceptibility loci, 5q23.3