Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

Frederik J. Hes*, Dina Ruano, Marry Nieuwenhuis, Carli M. Tops, Melanie Schrumpf, Maartje Nielsen, Petra E. A. Huijts, Juul T. Wijnen, Anja Wagner, Encarna B. Gomez Garcia, Rolf H. Sijmons, Fred H. Menko, Tom G. W. Letteboer, Nicoline Hoogerbrugge, Jan Harryvan, Ellen Kampman, Hans Morreau, Hans F. A. Vasen, Tom van Wezel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)55-60
JournalJournal of Medical Genetics
Issue number1
Publication statusPublished - Jan 2014


  • Cancer: colon
  • Clinical genetics
  • Genetic screening
  • counselling


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