Survival in women with MMR mutations and ovarian cancer; A multicentre study in Lynch Syndrome kindreds
- Eli Marie Grindedal (egrindedal{at}yahoo.no)
- Section for Inherited Cancer, Dep Medical Genetics, Rikshospitalet Medical Center, N-0310, Oslo, Norway
- Laura Renkonen-Sinisalo, Dr (laura.renkonen-sinisalo{at}hus.fi)
- Hans Vasen (hfavasen{at}stoet.nl)
- The Netherlands Foundation for the detection of Hereditary Tumours, Dep Gastroenterology, Leiden, Netherlands
- Paola Sala (paola.sala{at}istitutotumori.mi.it)
- Ignacio Blanco (iblanco{at}iconcologia.net)
- Jacek Gronwald (jgron{at}sci.pam.szczecin.pl)
- Jaran Apold (jaran.apold{at}helse-bergen.no)
- Diana M Eccles (d.m.eccles{at}soton.ac.uk)
- Ángel A Sánchez (angel.alonso.sanchez{at}cfnavarra.es)
- Heikki J Järvinen (laura.renkonen-sinisalo{at}hus.fi)
- Lucio Bertario (bertario{at}istitutotumori.mi.it)
- Gillian C Crawford (d.m.eccles{at}soton.ac.uk)
- Astrid T Stormorken (astridtenden.stormorken{at}ulleval.no)
- Section for Inherited Cancer, Dep Medical Genetics, Rikshospitalet Medical Center, N-0310, Oslo, Norway
- Lovise Maehle (l.o.mahle{at}medisin.uio.no)
- Section for Inherited Cancer, Dep Medical Genetics, Rikshospitalet Medical Center, N-0310, Oslo, Norway
- Pål Møller (moller.pal{at}gmail.com)
- Section for Inherited Cancer, Dep Medical Genetics, Rikshospitalet Medical Center, N-0310, Oslo, Norway
- Published Online First 26 July 2009
Abstract
Women 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 prophylaxis.
The 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.
Women who had ovarian cancer, and who tested positive for or were obligate carriers of an MMR-mutation, were included from eleven 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.
Among the 144 women included, 81.5% had FIGO stage 1 or 2 at diagnosis. Ten-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 years survival for ovarian cancer was 71.5%, and for all HNPCC/Lynch syndrome related cancers including ovarian cancer 47.3%.
In 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.
