Survival in women with MMR mutations and ovarian cancer: a multicentre study in Lynch syndrome kindreds

• Published in: Journal of medical genetics Vol. 47; no. 2; pp. 99 - 102
• Main Authors: Grindedal, Eli Marie, Renkonen-Sinisalo, Laura, Vasen, Hans, Evans, Gareth, Sala, Paola, Blanco, Ignacio, Gronwald, Jacek, Apold, Jaran, Eccles, Diana M, Sánchez, Ángel Alonso, Sampson, Julian, Järvinen, Heikki J, Bertario, Lucio, Crawford, Gillian C, Stormorken, Astrid Tenden, Maehle, Lovise, Moller, Pal
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.02.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; DNA Mismatch Repair; DNA-Binding Proteins - genetics; Female; Female genital diseases; Fundamental and applied biological sciences. Psychology; genetic epidemiology; genetics; Genetics of eukaryotes. Biological and molecular evolution; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; lynch syndrome; Medical genetics; Medical sciences; Middle Aged; MMR genes; Molecular and cellular biology; Mutation; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; Nuclear Proteins - genetics; oncology; Ovarian cancer; Ovarian Neoplasms - genetics; Retrospective Studies; survival; Tumors; Human; Hereditary nonpolyposis colorectal cancer; Rectal disease; Prognosis; Ovary cancer; Malignant tumor; Survival; Genetic disease; Female genital diseases; Colonic disease; Ovarian diseases; Digestive diseases; Intestinal disease; Adult; Female; Genetics; Mutation; Woman; Cancer
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg.2009.068130

BackgroundWomen with a germline mutation in one of the MMR genes MLH1, MSH2 or MSH6 reportedly have 4–12% lifetime risk of ovarian cancer, but there is limited knowledge on survival. Prophylactic bilateral salpingo-oophorectomy (PBSO) has been suggested for preventing this condition.AimThe purpose of this retrospective multicentre study was to describe survival in carriers of pathogenic mutations in one of the MMR genes, and who had contracted ovarian cancer.MethodsWomen who had ovarian cancer, and who tested positive for or were obligate carriers of an MMR mutation, were included from 11 European centres for hereditary cancer. Most women had not attended for gynaecological screening. Crude and disease specific survival was calculated by the Kaplan–Meier algorithm.ResultsAmong the 144 women included, 81.5% had FIGO stage 1 or 2 at diagnosis. 10 year ovarian cancer specific survival independent of staging was 80.6%, compared to less than 40% that is reported both in population based series and in BRCA mutation carriers. Disease specific 30 year survival for ovarian cancer was 71.5%, and for all hereditary non-polyposis colon cancer (HNPCC)/Lynch syndrome related cancers including ovarian cancer it was 47.3%.ConclusionsIn the series examined, infiltrating ovarian cancer in Lynch syndrome had a better prognosis than infiltrating ovarian cancer in BRCA1/2 mutation carriers or in the general population. Lifetime risk of ovarian cancer of about 10% and a risk of dying of ovarian cancer of 20% gave a lifetime risk of dying of ovarian cancer of about 2% in female MMR mutation carriers.