N07: Cancer Risks By Age And Gender And Survival After Cancer In Path_MSH6 Carriers: A Prospective Lynch Syndrome Database (PLSD) Report

J. Sampson1, J. P. Plazzer2, M. Dominguez-Valentin3, 4, S. Nakken4, T. Seppälä5, C. Engel6, S. Aretz6, H. K. Schackert6, W. Schmiegel6, N. Rahner6, M. von Knebel Doeberitz6, M. Loffler6, E. Holinski-Feder6, I. Bernstein7, L. Sunde7, M. Jenkins8, D. G. Evans9, J. Burn9, L. Bertario10, G. M. Cavestro10, A. Lindblom11, A. Della Valle12, H. Sijmons13, W. H. de Vos tot Nederveen Cappel13, L. Katz14, N. Gluck14, K. Heinimann15, C. A. Vaccaro16, F. Lopez-Koestner17, F. Balaguer18, E. Hovig4, F. Macrae19, G. Möslein6, J. P. Mecklin5, G. Capella18, Members of the PLSD project20, P Møller4, 21

1 – Cardiff University, UK. 2 – Australia & InSiGHT database. 3 – PLSD curator. 4 – Norway. 5 – Finland. 6 – Germany. 7 – Denmark. 8 – Australia. 9 – UK. 10 – Italy. 11 – Sweden. 12 – Uruguay. 13 – The Netherlands. 14 – Israel. 15 – Switzerland. 16 – Argentina. 17 – Chile. 18 – Spain. 19 – Australia. 20 – Interational. 21 – PLSD PI.

 

Aim: To determine cancer risks by age and gender and cancer survival in carriers of path_MSH6 variants.

Method: An independent cohort of class 4 or 5 path_MSH6 carriers was used to validate findings reported previously by PLSD. Data for individuals in the previous and validation cohorts who carried class 4 or 5 variants listed in the InSIGHT variant database were then combined and analysed by age and gender, deriving more precise risk and survival estimates to inform management.

Results: The validation cohort (N=425) provided 2,367 prospective observation years and confirmed previously reported cumulative risks for any cancer: 14% vs 18% at fifty years and 48% vs 53% at 70 years. The combined series of 841 carriers of class 4/5 path_MSH6 variants provided 5,205 prospective observation years. Cumulative risks at 75 years in males/females were: any cancer 42%/60%; colorectum 18%/20%; endometrium  NA/41%; ovary NA/11%; stomach, duodenum, bileduct, pancreas 8%/4%; ureter,_kidney  2%/6%; bladder 8%/1%; prostate 9%/NA; breast NA/14%; brain 2%/1%. Ten-year crude survival following cancer was: colon 100%; rectum 86% and endometrium 90%. See www.PLSD.eu to calculate risks for individual patients by age and gender.

Conclusion: MSH6-associated Lynch syndrome has distinct characteristics with a high risk of endometrial cancer compared to other organs.

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