Abstract
PurposeTo determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.MethodsThe Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.ResultsRisk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively.ConclusionLittle benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.
Highlights
Lynch syndrome (LS) is a common hereditary cancer predisposition syndrome, present in an estimated 1 in 300 individuals, based on prevalence of the underlying genetic abnormalities in the general population
LS is caused by pathogenic variants in one of four DNA mismatch repair (MMR) genes: path_MLH1, path_MSH2, path_MSH6, and path_PMS2, each of which result in different risks for cancers, including colorectal, endometrial, ovarian, stomach, small bowel, bile duct, pancreas, urinary tract, brain, and prostate cancer.[1,2,3,4,5]
There were no significant differences between the genes
Summary
Lynch syndrome (LS) is a common hereditary cancer predisposition syndrome, present in an estimated 1 in 300 individuals, based on prevalence of the underlying genetic abnormalities in the general population. LS is caused by pathogenic variants in one of four DNA mismatch repair (MMR) genes (path_MMR): path_MLH1, path_MSH2, path_MSH6, and path_PMS2, each of which result in different risks for cancers, including colorectal, endometrial, ovarian, stomach, small bowel, bile duct, pancreas, urinary tract, brain, and prostate cancer.[1,2,3,4,5] In women with LS, gynecological cancers are as common as gastrointestinal cancers. Clinical guidelines were similar for heterozygotes of all path_MMR genetic variants, endometrial cancer prognosis was assumed to be similar in heterozygotes and MMR variant-negative individuals, and the prognosis for ovarian cancer was assumed to be similar to ovarian cancer in path_BRCA1 heterozygotes. The recent Manchester International Consensus Group publication[6] described the risk for, and survival after, gynecological cancers in LS by genotype, as initially reported by the Prospective Lynch Syndrome Database (PLSD).[1,2,3,4,7] Later, the PLSD reported findings in an additional independent cohort of path_MMR heterozygotes that validated the results from its original cohort and allowed merger of both cohorts to obtain more precise risk estimates and calculation of 5year and 10-year crude survival after cancer.[2]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
