期刊
NATURE GENETICS
卷 46, 期 6, 页码 533-542出版社
NATURE PORTFOLIO
DOI: 10.1038/ng.2985
关键词
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资金
- US National Institutes of Health (NIH) [R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364]
- Vanderbilt University School of Medicine. Studies
- Asia Colorectal Cancer Consortium include the Shanghai Women's Health Study (US NIH) [R37CA070867]
- Shanghai Men's Health Study (US NIH) [R01CA082729]
- Shanghai Breast and Endometrial Cancer Studies (US NIH) [R01CA064277, R01CA092585]
- Shanghai Colorectal Cancer Study 3 (US NIH) [R37CA070867]
- Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project) [2011ZX09307-001-04]
- National Basic Research Program [2011CB504303]
- Natural Science Foundation of China [81072383]
- Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government)
- Hwasun Cancer Epidemiology Study Colon and Rectum Cancer (HCES-CRC)
- Korea Center for Disease Control and Prevention
- Aichi Colorectal Cancer Study [17015018, 221S0001]
- 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]
- Korea-Seoul Colorectal Cancer Study
- KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control) [1220180]
- Seoul RD Program [10526]
- GECCO
- CORECT
- CCFR
- 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, 01ER0814]
- HPFS (US NIH) [P01CA055075, UM1CA167552, R01137178, P50CA127003]
- NHS (US NIH) [R01137178, P50CA127003, P01CA087969]
- OFCCR (US NIH) [U01CA074783]
- PMH (US NIH) [R01CA076366]
- PHS (US NIH) [R01CA042182]
- Grants-in-Aid for Scientific Research [221S0001] Funding Source: KAKEN
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 x 10(-8) to 9.22 x 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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