Journal article

Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?

Shimelis Dejene Gemechu, Christine M van Vliet, Aung Ko Win, Jane C Figueiredo, Loic Le Marchand, Steven Gallinger, Polly A Newcomb, John L Hopper, Noralane M Lindor, Mark A Jenkins, James G Dowty



Individuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR = 1 corresponds to no POE and HR > 1 corresponds to higher risks for maternal mutations. For all MMR genes combined, the estimated POE HRs..

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Awarded by National Cancer Institute

Awarded by Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute

Funding Acknowledgements

This work was supported by grant U01 CA167551 from the National Cancer Institute and through cooperative agreements with the following Colon Cancer Family Registry sites: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735); Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800); Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783); Seattle Colorectal Cancer Family Registry (U01/U24 CA074794); University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806); and USC Consortium Colorectal Cancer Family Registry U01/U24 CA074799). The targeted minority recruitment was supported by grant R01 CA104132. Additional support for case ascertainment was provided from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute to the Fred Hutchinson Cancer Research Center (Control Nos. N01-CN-67009 and N01-PC-35142, and Contract No. HHSN2612013000121), the Hawai`i Department of Health (Control Nos. N01-PC-67001 and N01-PC-35137, and Contract No. HHSN26120100037C), and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California and HHSN261201000140C awarded to the Cancer Prevention Institute of California), the following US state cancer registries: AZ, CO, MN, NC and NH, and by the Victorian Cancer Registry, Australia and the Ontario Cancer Registry, Canada. A. K.W. is an NHMRC Career Development Fellow. M.A.J. is an NHMRC Senior Research Fellow. J.L.H. is an NHMRC Senior Principal Research Fellow. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR.