Clinical—Alimentary TractGermline MutY Human Homologue Mutations and Colorectal Cancer: A Multisite Case-Control Study
Section snippets
Methods
CRC patients and controls were recruited through the resources of the Colorectal Cancer Family Registry (C-CFR), a National Cancer Institute–supported consortium dedicated to the study of genetic and epidemiologic factors in CRC. Recruitment of cases and controls was undertaken at 6 international study sites and included the collection of family history, epidemiologic and pathologic data, and the collection of pathologic specimens and blood samples for genetic testing. Recruitment also included
Results
A total of 6769 subjects were genotyped for 9 MYH mutations. Interpretable MS results were obtained for 98%–99% of subjects for each mutation. A total of 132 subjects who did not have complete screening results for all 9 mutations and 24 cases with germline mutations in mismatch repair genes (MLH1, MSH2, and MSH6) were excluded from the analysis. Three hundred and fifty samples were submitted randomly for repeat MS testing and there was 100% concordance among duplicate genotyping results. The
Discussion
The mutYh, or MYH, gene is a member of the base-excision repair pathway involved in the detection and repair of oxidative DNA damage.30 Al-Tassan et al5 described 2 mutations in the MYH gene, Y165C and G382D, in a Welsh family with CRC and multiple adenomatous polyps. These 2 mutations appear to account for almost 90% of MYH mutations in Caucasian patients of Northern European ancestry. Additional mutations have been described in Caucasians13, 31, 32 and individuals of South Asian descent.7
The
Acknowledgments
The authors thank Ellen Shi for her assistance with the polytomous logistic regression.
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Conflict of interest The authors disclose no conflicts.
Funding This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011, the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and through cooperative agreements with members of the Colon Cancer Family Registry (CFRs) and P.I.s, and the National Cancer Institute of Canada (grant #13304 to S.G.) The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. M.E.C. is supported by an Interdisciplinary Health Research Team Scholarship through the Canadian Institutes of Health Research.