@article{bee6abcd8ec345019f4e3b559bc78480,
title = "Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk",
abstract = "Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10{\^ }'8 to 9.22 × 10 {\^a}{\^ }'21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.",
author = "Ben Zhang and Jia, {Wei Hua} and Koichi Matsuda and Kweon, {Sun Seog} and Keitaro Matsuo and Xiang, {Yong Bing} and Aesun Shin and Jee, {Sun Ha} and Kim, {Dong Hyun} and Qiuyin Cai and Jirong Long and Jiajun Shi and Wanqing Wen and Gong Yang and Yanfeng Zhang and Chun Li and Bingshan Li and Yan Guo and Zefang Ren and Ji, {Bu Tian} and Pan, {Zhi Zhong} and Atsushi Takahashi and Shin, {Min Ho} and Fumihiko Matsuda and Gao, {Yu Tang} and Oh, {Jae Hwan} and Soriul Kim and Ahn, {Yoon Ok} and Chan, {Andrew T.} and Jenny Chang-Claude and Slattery, {Martha L.} and Gruber, {Stephen B.} and Schumacher, {Fredrick R.} and Stenzel, {Stephanie L.} and Graham Casey and Kim, {Hyeong Rok} and Jeong, {Jin Young} and Park, {Ji Won} and Li, {Hong Lan} and Satoyo Hosono and Cho, {Sang Hee} and Michiaki Kubo and Shu, {Xiao Ou} and Zeng, {Yi Xin} and Wei Zheng",
note = "Funding Information: California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA). The CCFR consortium is represented by Graham Casey (Department of Preventive Medicine, University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA). We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik, R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; and P. Soule, H. Ranu, I. Devivo, D.J. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS and PHS, as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming. We thank C. Berg and P. Prorok of PLCO; T. Riley of Information Management Services, Inc.; B. O{\textquoteright}Brien of Westat, Inc.; B. Kopp and W. Shao of SAIC-Frederick; the WHI investigators (see https://www.whi.org/researchers/SitePages/Write%20a%20Paper. aspx) and the GECCO Coordinating Center. Participating studies (grant support) in the GECCO, CORECT and CCFR GWAS meta-analysis are GECCO (US NIH, U01CA137088 and R01CA059045), DALS (US NIH, R01CA048998), DACHS (German Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, 01KH0404 and 01ER0814), HPFS (US NIH, P01CA055075, UM1CA167552, R01137178 and P50CA127003), NHS (US NIH, R01137178, P50CA127003 and P01CA087969), OFCCR (US NIH, U01CA074783), PMH (US NIH, R01CA076366), PHS (US NIH, R01CA042182), VITAL (US NIH, K05CA154337), WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and 268200764316C) and PLCO (US NIH, Z01CP 010200, U01HG004446 and U01HG 004438). CORECT is supported by the National Cancer Institute as part of the GAME-ON consortium (US NIH, U19CA148107) with additional support from National Cancer Institute grants (R01CA81488 and P30CA014089), the National Human Genome Research Institute at the US NIH (T32HG000040) and the National Institute of Environmental Health Sciences at the US NIH (T32ES013678). CCFR is supported by the National Cancer Institute, US NIH under RFA CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators of the Australasian Colorectal Cancer Family Registry (US NIH, U01CA097735), the Familial Colorectal Neoplasia Collaborative Group (US NIH, U01CA074799) (University of Southern California), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (US NIH, U01CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (US NIH, U01CA074783), the Seattle Colorectal Cancer Family Registry (US NIH, U01CA074794) and the University of Hawaii Colorectal Cancer Family Registry (US NIH, U01CA074806). The GWAS work was supported by a National Cancer Institute grant (US NIH, U01CA122839). OFCCR was supported by a GL2 grant from the Ontario Research Fund, Canadian Institutes of Health Research and a Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J. Hudson and B.W. Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through support from the Ontario Ministry of Economic Development and Innovation. ASTERISK was funded by a Regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Fran{\c c}aises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne G{\'e}n{\'e}tique and the Ligue R{\'e}gionale Contre le Cancer (LRCC). PLCO data sets were accessed with approval through dbGaP (CGEMS prostate cancer scan, phs000207.v1.p1; CGEMS pancreatic cancer scan, phs000206.v4.p3; and GWAS of Lung Cancer and Smoking, phs000093.v2.p2, which was funded by Z01CP 010200, U01HG004446 and U01HG 004438 from the US NIH). Funding Information: The authors are solely responsible for the scientific content of this paper. The sponsors of this study had no role in study design, data collection, analysis or interpretation, writing of the report or the decision for submission. We thank all study participants and research staff of all parent studies for their contributions and commitment to this project, R. Courtney for DNA preparation, J. He for data processing and analyses, X. Guo for suggestions on bioinformatics analysis, and M.J. Daly and B.J. Rammer for editing and preparing the manuscript. The work at the Vanderbilt University School of Medicine was supported by US National Institutes of Health (NIH) grants R37CA070867, R01CA082729, R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. Studies (grant support) participating in the Asia Colorectal Cancer Consortium include the Shanghai Women{\textquoteright}s Health Study (US NIH, R37CA070867), the Shanghai Men{\textquoteright}s Health Study (US NIH, R01CA082729), the Shanghai Breast and Endometrial Cancer Studies (US NIH, R01CA064277 and R01CA092585; contributing only controls), Shanghai Colorectal Cancer Study 3 (US NIH, R37CA070867 and Ingram Professorship funds), the Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project, 2011ZX09307-001-04; the National Basic Research Program, 2011CB504303, contributing only controls; the Natural Science Foundation of China, 81072383, contributing only controls), the Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government), the Hwasun Cancer Epidemiology Study–Colon and Rectum Cancer (HCES-CRC; grants from the Korea Center for Disease Control and Prevention and the Jeonnam Regional Cancer Center), the Aichi Colorectal Cancer Study (Grant-in-Aid for Cancer Research, grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, 17015018 and 221S0001), the Korea-NCC (National Cancer Center) Colorectal Cancer Study (Basic Science Research Program through the National Research Foundation of Korea, 2010-0010276; National Cancer Center Korea, 0910220), the Korea-Seoul Colorectal Cancer Study (none reported) and the KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control, 1220180; Seoul R&D Program, 10526).",
year = "2014",
month = jun,
doi = "10.1038/ng.2985",
language = "English",
volume = "46",
pages = "533--542",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "6",
}
