Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age; a report from the Prospective Lynch Syndrome Database

摘要

Background: Most patients with a path_MMR variant gene variants (Lynch Syndrome, LS) now survive both their first and subsequent cancers. As a consequence, there is a growing number of older LS patients for whom limited information exists on cancer risk and survival. Objective and design: This observational, international, multicenter study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. Results: 3,119 patients were followed for a total of 24,475 years. Risks for colorectal cancer were 50%, 50% and 23% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 58% and 46%; for ovarian cancer 10%, 17% and 13%; for upper-gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 23%, 12% and 8%; for urinary tract cancers 9%, 28% and 12%; for prostate cancer 18%, 35% and 21%; and for brain tumours 1%, 6% and 1%, respectively. Ovarian cancer occurred mainly pre-menopausally. By contrast, upper-intestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall five-year survival for prostate cancer was 100%, bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had a lower risks for cancer.Conclusion: Carriers of pathogenic variants in different MMR genes 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 genetic variant. We have updated our open-access website www.lscarisk.org to facilitate this.