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

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.

Yan Guo | Ben Zhang | Min-Ho Shin | Gong Yang | Keitaro Matsuo | Stephen B Gruber | Sun Ha Jee | Jirong Long | Jenny Chang-Claude | Michiaki Kubo | Koichi Matsuda | Jae Hwan Oh | Jin-Young Jeong | Bingshan Li | Graham Casey | Atsushi Takahashi | Fumihiko Matsuda | Sang-Hee Cho | Andrew T Chan | Martha L Slattery | Wanqing Wen | Wei Zheng | C. Carlson | J. Chang-Claude | M. Hoffmeister | R. Hayes | S. Chanock | J. Potter | D. Seminara | S. Gruber | D. Duggan | K. Matsuda | G. Severi | S. Thibodeau | D. Conti | L. Le Marchand | F. Schumacher | E. Giovannucci | J. Long | W. Jia | X. Shu | Yu-tang Gao | Y. Xiang | W. Zheng | S. Berndt | G. Casey | J. Baron | M. Kubo | J. Park | J. Oh | S. Gallinger | K. Matsuo | Q. Cai | P. Newcomb | U. Peters | A. Chan | C. Fuchs | M. Jenkins | T. Rohan | D. Thomas | C. Hutter | W. Wen | W. Gauderman | S. Jee | L. Hsu | E. Jacobs | B. Zanke | E. White | A. Takahashi | F. Matsuda | R. Schoen | Bingshan Li | M. Slattery | Jian Gong | S. Küry | Gong Yang | M. Lemire | N. Lindor | Chun Li | Y. Zeng | Z. Pan | B. Ji | R. Haile | Soriul Kim | J. Figueiredo | M. Shin | B. Mukherjee | Yan Guo | A. Shin | S. Kweon | Hong-Lan Li | C. Edlund | Yi Lin | Jing Ma | B. Caan | T. Harrison | Sang-Hee Cho | Shuo Jiao | Dong-Hyun Kim | S. Bézieau | P. Campbell | Keith Curtis | Ben Zhang | Yanfeng Zhang | Jiajun Shi | R. Green | L. Raskin | S. Hosono | H. Kim | Li Li | Xiao-Ou Shu | Yu-Tang Gao | Fredrick R Schumacher | Yanfeng Zhang | Sun-Seog Kweon | Qiuyin Cai | Yong-Bing Xiang | Yoon-Ok Ahn | Dong-Hyun Kim | Yi-Xin Zeng | Satoyo Hosono | Wei-Hua Jia | Bu-Tian Ji | Z. Ren | Y. Ahn | Zhi-Zhong Pan | Aesun Shin | Zefang Ren | Jiajun Shi | Ji Won Park | F. Manion | Duncan C. Thomas | Stephanie L. Stenzel | Jin-Young Jeong | Chun Li | Soriul Kim | Stephanie L Stenzel | Hyeong-Rok Kim | Hong-Lan Li | H. Brenner | T. Hudson | J. Hopper | A. Chan | J. Gong | Sang‐Hee Cho | Yu-Tang Gao | D. J. Hunter | V. Moreno | John Harju | C. Qu | Rebecca D. Jackson | John A Sonja I Stéphane Hermann Bette J Christopher S G Baron Berndt Bezieau Brenner Caan Carlson Ca | Kendra Peter T Graham David V Christopher K Jane W James Blalock Campbell Casey Conti Edlund Figuei | K. Blalock | Stephanie L Stenzel | Chang-Claude Jenny | M. Kubo | M. Jenkins | Yu-Tang Gao | Yu-Tang Gao | Andrew T. Chan | Andrew T Chan | Jenny Chang-Claude | M L Slattery | Stephen B Gruber | Graham Casey | L. Hsu | J. Chang-Claude | A. T. Chan | S. Gruber | Andrew T. Chan

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