Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis. Issue 1 (19th November 2013)

• Record Type: Journal Article
• Authors: Hes, Frederik J; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E A; Wijnen, Juul T; Wagner, Anja; García, Encarna B Gómez; Sijmons, Rolf H; Menko, Fred H; Letteboer, Tom G W; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F A; van Wezel, Tom
• Is Part Of: Journal of medical genetics. Volume 51:Issue 1(2014)
• Page Start: 55
• Page End: 60
• Publication Date: 2013-11-19
• Subjects: Cancer: colon -- Clinical genetics -- Genetic screening/counselling; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2013-102000
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH . However, in about 20–30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas. Methods: We analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs). Results: We found a statistically significant association with two of the variants tested: rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC. Conclusions: These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance.