Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

Hansong Wang; Terrilea Burnett; Suminori Kono; Christopher A Haiman; Motoki Iwasaki; Lynne R Wilkens; Lenora W M Loo; David Van Den Berg; Laurence N Kolonel; Brian E Henderson; Temitope O Keku; Robert S Sandler; Lisa B Signorello; William J Blot; Polly A Newcomb; Mala Pande; Christopher I Amos; Dee W West; Stéphane Bézieau; Sonja I Berndt; Brent W Zanke; Li Hsu; Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO); Noralane M Lindor; Robert W Haile; John L Hopper; Mark A Jenkins; Steven Gallinger; Graham Casey; Colon Cancer Family Registry (CCFR); Stephanie L Stenzel; Fredrick R Schumacher; Ulrike Peters; Stephen B Gruber; Colorectal Transdisciplinary Study (CORECT); Shoichiro Tsugane; Daniel O Stram; Loïc Le Marchand

doi:10.1038/ncomms5613

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

Nat Commun. 2014 Aug 8:5:4613. doi: 10.1038/ncomms5613.

Authors

Hansong Wang¹, Terrilea Burnett¹, Suminori Kono², Christopher A Haiman³, Motoki Iwasaki⁴, Lynne R Wilkens¹, Lenora W M Loo¹, David Van Den Berg³, Laurence N Kolonel¹, Brian E Henderson³, Temitope O Keku⁵, Robert S Sandler⁵, Lisa B Signorello⁶, William J Blot⁷, Polly A Newcomb⁸, Mala Pande⁹, Christopher I Amos¹⁰, Dee W West¹¹, Stéphane Bézieau¹², Sonja I Berndt¹³, Brent W Zanke¹⁴, Li Hsu⁸; Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO); Noralane M Lindor¹, Robert W Haile¹, John L Hopper¹, Mark A Jenkins¹, Steven Gallinger¹⁵, Graham Casey³; Colon Cancer Family Registry (CCFR); Stephanie L Stenzel³, Fredrick R Schumacher¹, Ulrike Peters⁸, Stephen B Gruber¹; Colorectal Transdisciplinary Study (CORECT); Shoichiro Tsugane⁴, Daniel O Stram³, Loïc Le Marchand¹

Collaborators

John A Baron, Sonja I Berndt, Stéphane Bezieau, Hermann Brenner, Bette J Caan, Christopher S Carlson, Graham Casey, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, David V Conti, Keith Curtis, David Duggan, Charles S Fuchs, Steven Gallinger, Edward L Giovannucci, Stephen B Gruber, Robert W Haile, Tabitha A Harrison, Richard B Hayes, Michael Hoffmeister, John L Hopper, Li Hsu, Thomas J Hudson, David J Hunter, Carolyn M Hutter, Rebecca D Jackson, Mark A Jenkins, Shuo Jiao, Sébastien Küry, Loic Le Marchand, Mathieu Lemire, Noralane M Lindor, Jing Ma, Polly A Newcomb, Ulrike Peters, John D Potter, Conghui Qu, Thomas Rohan, Robert E Schoen, Fredrick R Schumacher, Daniela Seminara, Martha L Slattery, Stephen N Thibodeau, Emily White, Brent W Zanke, John A Baron, Graham Casey, Duncan C Thomas, Fredrick R Schumacher, David V Conti, Michelle Cotterchio, Dave Duggan, Steven Gallinger, Robert Haile, John L Hopper, Mark A Jenkins, Jeremy Jass, Loic Le Marchand, John Grove, Noralane M Lindor, Steve Thibodeau, Polly A Newcomb, John D Potter, Sheri Schully, Daniela Seminara, Kendra Blalock, Peter T Campbell, Graham Casey, David V Conti, Christopher K Edlund, Jane Figueiredo, W James Gauderman, Jian Gong, Roger C Green, Stephen B Gruber, John F Harju, Tabitha A Harrison, Eric J Jacobs, Mark A Jenkins, Shuo Jiao, Li Li, Yi Lin, Frank J Manion, Victor Moreno, Bhramar Mukherjee, Ulrike Peters, Leon Raskin, Fredrick R Schumacher, Daniela Seminara, Gianluca Severi, Stephanie L Stenzel, Duncan C Thomas

Affiliations

¹ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96822, USA.
² Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8581, Japan.
³ Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
⁴ Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
⁵ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
⁶ 1] Department of Epidemiology, Harvard School of Public Health, and the Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Dana-Farber/Harvard Cancer Center, Boston, Massachusetts 02115, USA.
⁷ 1] Division of Epidemiology, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37235, USA [2] International Epidemiology Institute, Rockville, Maryland 20850, USA.
⁸ Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 19024, USA.
⁹ Department of Gastroenterolgy-Research, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
¹⁰ Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03755, USA.
¹¹ Cancer Prevention Institute of California, Fremont, California 94538, USA.
¹² Service de Génétique Médicale, CHU Nantes, 44093 Nantes, France.
¹³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
¹⁴ Division of Hematology, Faculty of Medicine, University of Ottawa and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1J8M5.
¹⁵ Cancer Care Ontario, Toronto, Ontario, Canada M5G 2L3.

Abstract

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10(-8)) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10(-9)), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Alleles
Asian People / genetics
Black or African American / genetics
Case-Control Studies
Chromosome Mapping
Colorectal Neoplasms / ethnology*
Colorectal Neoplasms / genetics*
Genetic Loci
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Genotype
Humans
Japan
Polymorphism, Single Nucleotide
Qb-SNARE Proteins / genetics*
United States
White People / genetics

Substances

Qb-SNARE Proteins
VTI1A protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding