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

TitleLarge-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Publication TypeJournal Article
Year of Publication2014
AuthorsZhang, B, Jia, W-H, Matsuda, K, Kweon, S-S, Matsuo, K, Xiang, Y-B, Shin, A, Jee, SHa, Kim, D-H, Cai, Q, Long, J, Shi, J, Wen, W, Yang, G, Zhang, Y, Li, C, Li, B, Guo, Y, Ren, Z, Ji, B-T, Pan, Z-Z, Takahashi, A, Shin, M-H, Matsuda, F, Gao, Y-T, Oh, JHwan, Kim, S, Ahn, Y-O, Chan, AT, Chang-Claude, J, Slattery, ML, Gruber, SB, Schumacher, FR, Stenzel, SL, Casey, G, Kim, H-R, Jeong, J-Y, Park, JWon, Li, H-L, Hosono, S, Cho, S-H, Kubo, M, Shu, X-O, Zeng, Y-X, Zheng, W
Corporate Authors, ,
JournalNat Genet
Volume46
Issue6
Pagination533-42
Date Published2014 Jun
ISSN1546-1718
KeywordsAsian Continental Ancestry Group, Case-Control Studies, China, Chromosome Mapping, Colorectal Neoplasms, Computational Biology, Female, Gene Expression Profiling, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Japan, Male, Neoplasm Metastasis, Polymorphism, Single Nucleotide, Republic of Korea, 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(-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.

DOI10.1038/ng.2985
Alternate JournalNat. Genet.
PubMed ID24836286
PubMed Central IDPMC4068797
Grant ListHHSN268200764316C / / PHS HHS / United States
HHSN268201100001C / / PHS HHS / United States
HHSN268201100002C / / PHS HHS / United States
HHSN268201100003C / / PHS HHS / United States
HHSN268201100004C / / PHS HHS / United States
HHSN268201100046C / / PHS HHS / United States
HHSN271201100004C / / PHS HHS / United States
K05CA154337 / CA / NCI NIH HHS / United States
P01CA055075 / CA / NCI NIH HHS / United States
P01CA087969 / CA / NCI NIH HHS / United States
P30CA014089 / CA / NCI NIH HHS / United States
P50CA127003 / CA / NCI NIH HHS / United States
R01 CA059045 / CA / NCI NIH HHS / United States
R01 CA082729 / CA / NCI NIH HHS / United States
R01 CA122364 / CA / NCI NIH HHS / United States
R01 CA124558 / CA / NCI NIH HHS / United States
R01 CA148667 / CA / NCI NIH HHS / United States
R01137178 / / PHS HHS / United States
R01CA042182 / CA / NCI NIH HHS / United States
R01CA048998 / CA / NCI NIH HHS / United States
R01CA059045 / CA / NCI NIH HHS / United States
R01CA064277 / CA / NCI NIH HHS / United States
R01CA076366 / CA / NCI NIH HHS / United States
R01CA082729 / CA / NCI NIH HHS / United States
R01CA092585 / CA / NCI NIH HHS / United States
R01CA122364 / CA / NCI NIH HHS / United States
R01CA124558 / CA / NCI NIH HHS / United States
R01CA148667 / CA / NCI NIH HHS / United States
R01CA81488 / CA / NCI NIH HHS / United States
R37 CA070867 / CA / NCI NIH HHS / United States
R37CA070867 / CA / NCI NIH HHS / United States
T32ES013678 / ES / NIEHS NIH HHS / United States
T32HG000040 / HG / NHGRI NIH HHS / United States
U01 CA137088 / CA / NCI NIH HHS / United States
U01CA074783 / CA / NCI NIH HHS / United States
U01CA074794 / CA / NCI NIH HHS / United States
U01CA074799 / CA / NCI NIH HHS / United States
U01CA074800 / CA / NCI NIH HHS / United States
U01CA074806 / CA / NCI NIH HHS / United States
U01CA097735 / CA / NCI NIH HHS / United States
U01CA122839 / CA / NCI NIH HHS / United States
U01CA137088 / CA / NCI NIH HHS / United States
U01HG 004438 / HG / NHGRI NIH HHS / United States
U01HG004446 / HG / NHGRI NIH HHS / United States
UM1 CA173640 / CA / NCI NIH HHS / United States
UM1CA167552 / CA / NCI NIH HHS / United States
Z01CP 010200 / CP / NCI NIH HHS / United States
People: 
Frank Manion
University of Michigan Comprehensive Cancer Center at North Campus Reserach Complex
1600 Huron Parkway, Bldg 100, Rm 100 
Mailing Address: 2800 Plymouth Rd, NCRC 100-1004
Ann Arbor, MI 48109-2800 
Ph. (734) 764-8848 Fax. (734) 615-0517
Please acknowledge the Cancer Center Support Grant (P30 CA046592) when publishing manuscripts or abstracts that utilized the services of the University of Michigan's Comprehensive Cancer Center's Shared Resource: Cancer Informatics.
Suggested language: "Research reported in this [publication/press release] was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592."

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