Risks of Colorectal and Other Cancers After Endometrial Cancer for Women With Lynch Syndrome.

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Affiliations of authors: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology (AKW, JLH, MAJ) and Department of Medicine (IW), The University of Melbourne, Parkville, Victoria, Australia; Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ (NML); Genetic Medicine (IW) and Colorectal Medicine and Genetics (FAM), The Royal Melbourne Hospital, Parkville, Victoria, Australia; Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia (KMT); Cancer and Population Studies Group (DDB, JPY, CR) and Conjoint Gastroenterology Laboratory, Pathology Queensland, Clinical Research Centre of Royal Brisbane and Women's Hospital Research Foundation (BL), Queensland Institute of Medical Research, Herston, Queensland, Australia; Department of Molecular and Cellular Pathology (CR) and School of Medicine (BL), University of Queensland, Herston, Queensland, Australia; Department of Gastroenterology and Hepatology, The Royal Brisbane and Women's Hospital, Brisbane, Australia (BL); Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia (GGG); Genetic Services of Western Australia and School of Paediatrics and Child Health, University of Western Australia, Perth, Australia (JG); New Zealand Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand (SP); Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand (SP); Department of Colorectal Surgery, Digestive Disease Institute, and Cancer Biology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH (MFK); Department of Medicine, University of North Carolina, Chapel Hill, NC (JAB); Denver VA Medical Center, School of Medicine, University of Colorado, Denver, CO (DJA); University of Hawaii Cancer Center, Honolulu, HI (LLM); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (SG); Cancer Care Ontario, Toronto, Ontario, Canada (SG); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (RWH); Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA (PAN).

Abstract

BackgroundLynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer. We estimated cancer risks following an endometrial cancer diagnosis for women carrying MMR gene mutations.MethodsWe obtained data from the Colon Cancer Family Registry for a cohort of 127 women who had a diagnosis of endometrial cancer and who carried a mutation in one of four MMR genes (30 carried a mutation in MLH1, 72 in MSH2, 22 in MSH6, and 3 in PMS2). We used the Kaplan-Meier method to estimate 10- and 20-year cumulative risks for each cancer. We estimated the age-, country-, and calendar period-specific standardized incidence ratios (SIRs) for each cancer, compared with the general population.ResultsFollowing endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers: colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%); cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%); urinary bladder cancer (9%, 95% CI = 2% to 17%); and breast cancer (11%, 95% CI = 4% to 19%). Compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (SIR = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14).ConclusionsWomen with Lynch syndrome who are diagnosed with endometrial cancer have increased risks of several cancers, including breast cancer.