Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.
Objective and design This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age.
Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer.
Conclusion Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
- cancer prevention
- clinical trials
- colorectal cancer screening
- inherited cancers
- HNPCC syndrome
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Contributors PåMø: Designed the study, managed the database and computed the results.PåMø, Julian Sampson and GC wrote the manuscript.EH, SN, EARø and KT calculated the confidence intervals to the cumulative incidences.EH and SN constructed the website calculating individual risks.All: Participated in study design, interpreting of results, commenting the manuscript and approved the final manuscript.
Competing interests John Burn has a patent for high speed low cost tumour profiling pending to John Burn and QuantuMDx.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The report is based on The Prospective Lynch Syndrome Database which is a joint venture by the contribuotrs and endorsed by EHTG (mallorca-gropu.org) Group and InSiGTH (insight-group.org). Formal ownerships and development of the activities will be discussed at this year joint meeting for EHTG and InSiGHT in Florence July 5th-8th this year. All interested are wellcomed to join.
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