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Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.

About this Publication
Title
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Pubmed ID
24836286 (View this publication on the PubMed website)
Publication
Nat. Genet. 2014 Jun; Volume 46 (Issue 6): Pages 533-42
Authors
Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, Shin A, Jee SH, Kim DH, Cai Q, Long J, Shi J, Wen W, Yang G, Zhang Y, Li C, Li B, Guo Y, Ren Z, Ji BT, ...show more Pan ZZ, Takahashi A, Shin MH, Matsuda F, Gao YT, Oh JH, Kim S, Ahn YO, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Chan AT, Chang-Claude J, Slattery ML, Colorectal Transdisciplinary (CORECT) Study, Gruber SB, Schumacher FR, Stenzel SL, Colon Cancer Family Registry (CCFR), Casey G, Kim HR, Jeong JY, Park JW, Li HL, Hosono S, Cho SH, Kubo M, Shu XO, Zeng YX, Zheng W
Affiliations
  • Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 1] Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea. [2] Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
  • Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan.
  • Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
  • 1] Molecular Epidemiology Branch, National Cancer Center, Goyang-si, South Korea. [2] Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
  • Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
  • Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
  • Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
...show more
  • Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • School of Public Health, Sun Yat-sen University, Guangzhou, China.
  • Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
  • Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
  • Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Center for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea.
  • Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
  • 1] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
  • University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
  • Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea.
  • 1] Center for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea. [2] Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
  • Department of Hemato-oncology, Chonnam National University Medical School, Gwangju, South Korea.
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(-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.

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