A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1

Mathieu Lemire, Conghui Qu, Lenora W.M. Loo, Syed H.E. Zaidi, Hansong Wang, Sonja I. Berndt, Stéphane Bézieau, Hermann Brenner, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Mengmeng Du, Christopher K. Edlund, Steven Gallinger, Robert W. Haile, Tabitha A. Harrison, Michael Hoffmeister, John L. Hopper, Lifang Hou, Li HsuEric J. Jacobs, Mark A. Jenkins, Jihyoun Jeon, Sébastien Küry, Li Li, Noralane M. Lindor, Polly A. Newcomb, John D. Potter, Gad Rennert, Anja Rudolph, Robert E. Schoen, Fredrick R. Schumacher, Daniela Seminara, Gianluca Severi, Martha L. Slattery, Emily White, Michael O. Woods, Michelle Cotterchio, Loïc Le Marchand, Graham Casey, Stephen B. Gruber, Ulrike Peters, Thomas J. Hudson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 × 10−10; odds ratio estimated by re-including all controls (OR) = 0.87, 95 % confidence interval (CI) 0.83–0.91; minor allele frequency (MAF) = 13 %]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 % CI 0.77–0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 × 10−8).

Original languageEnglish (US)
Pages (from-to)1249-1262
Number of pages14
JournalHuman Genetics
Issue number11-12
StatePublished - Sep 24 2015
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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