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Annals of Oncology Advance Access published online on May 27, 2009
Annals of Oncology, doi:10.1093/annonc/mdp023
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant

M. J. Hall1, E. Liberman2,3, O. Dulkart2,3, L. Galazan2, E. Sagiv2,3, E. Shmueli3,4, D. Kazanov2, A. Hallak3,5, M. Moshkowitz3,5, A. Figer3,4, S. Kraus2, M. Inbar3,4, A. I. Neugut1 and N. Arber2,5,*

1 Departments of Medicine and Epidemiology, College of Physicians and Surgeons, and the Mailman School of Public Health, Columbia University, New York, NY, USA
2 Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center
3 Sackler Faculty of Medicine, Departments of
4 Oncology
5 Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel Aviv, Israel

* Correspondence to: Dr N. Arber, Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64236, Israel. Tel: +972-3-697-4968; Fax: +972-3-695-0339; E-mail: narber{at}post.tau.ac.il

Background: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case–control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center.

Materials and Methods: All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (±biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated.

Results: The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0–9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8–9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8–5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0–10.8).

Conclusions: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews.

APC gene, colorectal cancer, E1317Q, hereditary risk

Received for publication October 15, 2008. Revision received January 14, 2009. Accepted for publication January 16, 2009.


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