Abstract:
: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 were 1.02 (95% confidence interval (CI) 0.75-1.39, p = 0.9) for male colorectal cancer, 1.12 (95% CI 0.81-1.54, p = 0.5) for female colorectal cancer and 0.84 (95% CI 0.52-1.36, p = 0.5) for endometrial cancer. Separate results for each MMR gene were similar. Therefore, despite being well-powered, our study did not find any evidence that cancer risks for MMR gene mutation carriers depend on the parent-of-origin of the mutation. Based on current evidence, we do not recommend that POEs be incorporated into the clinical guidelines or advice for such carriers.
journal_name
Fam Cancerjournal_title
Familial cancerauthors
Gemechu SD,van Vliet CM,Win AK,Figueiredo JC,Le Marchand L,Gallinger S,Newcomb PA,Hopper JL,Lindor NM,Jenkins MA,Dowty JGdoi
10.1007/s10689-020-00167-4subject
Has Abstractpub_date
2020-07-01 00:00:00pages
215-222issue
3eissn
1389-9600issn
1573-7292pii
10.1007/s10689-020-00167-4journal_volume
19pub_type
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