A Rare Missense Variant in TCF7L2 Associates with Colorectal Cancer Risk by Interacting with a GWAS-Identified Regulatory Variant in the MYC Enhancer

Cancer Research
Jiang ChangXiaoping Miao

Abstract

Genome-wide association studies (GWAS) of colorectal cancer have identified several common susceptible variants in gene regulatory regions. However, low-frequency or rare coding risk variants have not been systematically investigated in patients with colorectal cancer from Chinese populations. In this study, we performed an exome-wide association analysis with 1,062 patients with colorectal cancer and 2,184 controls from a Chinese population. Promising associations were further replicated in two replication sets: replication stage I with 2,478 cases and 3,880 controls, and replication stage II with 3,761 cases and 4,058 controls. We identified two variants significantly associated with colorectal cancer risk: a novel rare missense variant in TCF7L2 [rs138649767, OR = 2.08, 95% confidence interval (CI): 1.69-2.57, P = 5.66 × 10-12] and a previous European GWAS-identified 3'-UTR variant in ATF1 (rs11169571, OR = 1.18, 95% CI: 1.13-1.24, P = 1.65 × 10-12). We found a significant interaction between the TCF7L2 missense variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that TCF7L2 with rs138649767-A allele harbored...Continue Reading

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Citations

Jul 2, 2019·Journal of Clinical Laboratory Analysis·Xiaofeng GaoGuochang Liu
Dec 28, 2019·Journal of Cellular and Molecular Medicine·Juntao KeXiaoping Miao
Oct 18, 2018·Nucleic Acids Research·Jianbo TianXiaoping Miao
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Sep 15, 2018·Nucleic Acids Research·Yang YangXiaoping Miao
May 16, 2019·Experimental Hematology & Oncology·Tianyou YangYan Zou
May 8, 2020·Journal of Oncology·Zhi-Gang GaoZhen-Jun Wang
Jan 29, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Juntao KeXiaoping Miao
Nov 25, 2018·Trends in Cancer·Olga Lancho, Daniel Herranz
Feb 26, 2021·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Marco MatejcicStephanie L Schmit

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