Format

Send to

Choose Destination
Carcinogenesis. 2018 May 3;39(5):652-660. doi: 10.1093/carcin/bgy026.

GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12.

Author information

1
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
2
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
3
Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
4
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
5
Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
6
Oncology Master Progam, University Claude Bernard, Lyon I, Lyon, France.
7
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
8
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan.
9
Department of Gastroenterological Surgery and Graduate School of Medicine, Osaka University, Osaka, Japan.
10
Department of Medical Data Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
11
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
12
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
13
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
14
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
15
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
16
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan.
17
Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
18
Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
19
Project Division of International Advanced Medical Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
20
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
21
Department of Medicine, The University of Chicago, IL, USA.
22
Department of Surgery, The University of Chicago, IL, USA.
23
Center for Personalized Therapeutics, The University of Chicago, IL, USA.

Abstract

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC loci. However, most of the previous studies were conducted in European population, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6692 cases and 27 178 controls followed by a replication analysis using more than 11 000 case-control samples. We found the significant association of 10 loci (P < 5 × 10-8), including 2 novel loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 × 10-9 and odds ratio = 1.107 with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668, P = 4.47 × 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35 previously reported single nucleotide polymorphisms (SNPs) in 24 regions were validated in the Japanese population (P < 0.05) with the same risk allele as in the previous studies. SNP rs6065668 was significantly associated with TOX2 expression in the sigmoid colon. In addition, nucleotide substitutions in the regulatory region of TOX2 were predicted to alter the binding of several transcription factors, including KLF5. Our findings elucidate the important role of genetic variations in the development of CRC in the Japanese population.

PMID:
29471430
DOI:
10.1093/carcin/bgy026

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center