Screening of BMPR1a for pathogenic mutations in familial colorectal cancer type X families from Newfoundland
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The Canadian province of Newfoundland and Labrador (NL) reports one of the highest incidence rates of familial colorectal cancer (CRC) worldwide. The NL population is an invaluable resource for studying genetic disorders because of a unique ancestry, and a willingness to participate in research studies. Familial colorectal cancer type X (FCCTX) describes a cluster of families with strong predisposition for CRC, of unknown etiology. A putative link between FCCTX and BMPR1a mutations has been identified in the Finnish population; however these findings have not been independently replicated. To investigate a potential connection between BMPR1a and FCCTX, we screened a cohort of 22 probands from unrelated NL FCCTX families using Sanger sequencing. This analysis did not independently replicate findings seen in Finland; as no candidate pathogenic BMPR1a mutations were uncovered. Our findings highlight that BMPR1a mutations are not a major contributor of FCCTX incidence in NL. Further investigation of additional FCCTX populations may assist in delineating a role for BMPR1a, if any, in FCCTX globally.
KeywordsBMPR1a Familial colorectal cancer type X Candidate gene Newfoundland and Labrador
The authors declare they hold no conflict of interest with respect to this work. We would foremost like to thank the study participants who donated their time, personal information and family histories. Their support is integral to our ongoing research. DRE generated and analyzed DNA sequence data using laboratory protocols and analysis software. He assisted in reviewing patient phenotypic information, performed a literature review, and prepared the manuscript. JSG collected the phenotypic information for each patient over a period of several decades and reviewed the manuscript. MOW conceived of the study, participated in study design and supervised the collection of molecular and genetic data. All authors read and approved the final manuscript. This work was funded by the Research and Development Corporation of Newfoundland and Labrador (RDCNL), and the Canadian Cancer Society Research Institute (CCSRI).
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