N40: Validated And Updated Risks For And Survival After Cancer By Age And Gender In Path_MSH2 Carriers; A Prospective Lynch Syndrome Database (PLSD) Report

P. Møller1, J. P. Plazzer2, T. Seppälä3, M. Dominguez-Valentin4, S. Nakken5, C. Engel6, S. Aretz7, H. K. Schackert8, W. Schmiegel9, N. Rahner10, M. von Knebel Doeberitz11, M. Löffler12, I. Bernstein13, L. Sunde13, M. Jenkins14, D. G. Evans15, F. Balaguer16, E. Holinski-Feder17, J. Burn18, L. Bertario19, A. Lindblom20, A. Della Valle21, R. H. Sijmons22, L. Katz23, W. H. de Vos tot Nederveen Cappel24, K. Heinimann25, N. Gluck23, C. A. Vaccaro26, F. Lopez-Koestner27, G. Martina Cavestro19, E. Hovig5, F. Macrae28, G. Möslein29, J. P. Mecklin3, J. Sampson30, G. Capella16

1 – PI to the PLSD, Oslo University Hospital Norway and University of Witten-Herdecke Germany. 2 – InSiGHT database. 3 – Finland. 4 – PLSD curator Norway. 5 – Norway. 6 – German HNPCC consortium. 7 – University of Bonn. 8 – University of Dresden. 9 – University of Bochum. 10 – University of Düsseldorf. 11 – University of Heidelberg. 12 – University of Leipzig. 13 – Danish HNPCC Registry. 14 – Colon Cancer Family Registry Australia, USA, Canada. 15 – Manchester, UK. 16 – Spain. 17 – Münich, Germany. 18 – Newcastle, UK. 19 – Italy. 20 – Sweden. 21 – Uruguay. 22 – Groningen, Holland. 23 – Israel. 24 – Leiden, Holland. 25 – Switzerland. 26 – Argentina. 27 – Chile. 28 – Melbourne, Australia. 29 – Germany. 30 – Cardiff, UK.


Aim: Determine average risks for and survival after cancer in path_MSH2 carriers.

Method: Previously reported results were validated in an independent series of path_MSH2 carriers followed-up by colonoscopy. We combined results merging former and present series including only carriers with pathogenic class 4 or 5 variants listed in the InSiGHT database.

Results: The validation series including 11,684 observation years confirmed previously published cumulative risk for any cancer: at fifty years 35% compared to 37%, and at 75 years 79% compared to 80%. Combined series of carriers of path_MSH2 variants included 19,888 prospective observation years. Cumulative risk for cancer in specific organs or group of organs at 75 years in males/females were: Any cancer 73%/82%; colon_rectum 49%/45%; endometrium  -/47%; ovaries -/17%; stomach_duodenum_bileduct_pancreas 19%/12%; ureter_kidney  17%/18%; urinary bladder 12%/8%; prostate 22%/-; breast -/14%; brain 7%/3%. Ten-year crude survival after cancer in different organs were: colon 94%; endometrium 86%; ovaries 81%; ureter_kidney 65%; urinary bladder 72%; prostate 51%, breast 74%; brain 18%. See www.PLSD.eu for risk determination in any single patient by age and gender.

Conclusion: The PLSD and InSiGHT databases are complementary: PLSD reports prospectively observed average risks and survival in carriers of variants determined to be pathogenic by InSiGHT.