Cancer risk and survival in <i>path_MMR</i> carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.

Abstract

Most patients with <i>path_MMR</i> 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. This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in <i>path_MMR</i> carriers up to 75 years of age. 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_<i>MLH1</i>, path_<i>MSH2</i> and path_<i>MSH6</i> 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%. <i>Path_PMS2</i> carriers had lower risk for cancer. Carriers of different <i>path_MMR</i> 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 <i>path_MMR</i> variant. We have updated our open-access website www.lscarisk.org to facilitate this.