N37: Cancer Incidences By Age In Path_PMS2 Carriers: A Report From The Prospective Lynch Syndrome Database (PLSD)

M. Dominguez-Valentin1, S. W. Ten Broeke2, J. P. Plazzer3, T. Seppälä4, S. Nakken1, M. A. Jenkins5, R. H. Sijmons6, G. Capella7, C. Engel8, S. Aretz9, L. Sunde10, I. Bernstein11, D. G. Evans12, J. Burn13, M. Greenblatt14, F. Balaguer15, M. Grazia Tibiletti16, E. Holinski-Feder17, H. K. Schackert18, W. Schmiegel19, N. Rahner20, M. Löffler8, F. Macrae3, J. Sampson21, H. Thomas22, A. Lindblom23, W. H. de Vos tot Nederveen Cappel24, F. Lopez-Koestner25, A. Della Valle26, E. Hovig1, G. Möslein27, J. P. Mecklin28, M. Nielsen2, P. Møller1, 29, 30

1 – Oslo University Hospital, Oslo, Norway. 2 – Leiden University Medical Center, The Netherlands. 3 – Melbourne University, Melbourne, Australia. 4 – University of Helsinki, Helsinki, Finland. 5 – Colon Cancer Family Registry, Australia. 6 – University Medical Center Groningen, Groningen, The Netherlands. 7 – L’Hospitalet de Llobregat, Barcelona, Spain.8 – University of Leipzig, Leipzig, Germany. 9 – University of Bonn, Bonn, Germany. 10 – Aarhus University Hospital, Denmark. 11 – Aalborg University Hospital, Aalborg, Denmark. 12 – University of Manchester, London, UK. 13 – Newcastle University, Newcastle upon Tyne, UK. 14 – University of Vermont College of Medicine, USA. 15 – Universitat de Barcelona, Barcelona, Spain. 16 – Università dell’Insubria, Varese, Italy. 17 – Center of Medical Genetics, Munich, Germany. 18 – University of Dresden, Germany. 19 – University of Bochum, Germany. 20 – University of Düsseldorf. 21 – Cardiff University School of Medicine, Heath Park, UK. 22 – Imperial College London, London, UK. 23 – Karolinska Institutet, Stockholm, Sweden. 24 – Isala Clinics, Zwolle, The Netherlands. 25 – Clinica Las Condes, Chile. 26 – Hospital de las Fuerzas Armadas, Uruguay. 27 – University Witten-Herdecke, Wuppertal, Germany. 28 – University of Jyväskylä, Jyväskylä, Finland. 29 – PLSD PI. 30 – Witten-Herdecke, Germany.


Aim: Determine average risks for cancer in path_PMS2 carriers.

Method: Prospectively observed cancers in carriers of PMS2 variants classified as pathogenic (class 4/5) in the InSiGHT database.

Results: 407 carriers were prospectively observed for 2239 years and they underwent regular surveillance and if needed polypectomies. Cumulative incidences for cancer at 50/75 years of age were: Any cancer 8% (95% CI 0%-19%)/32% (95% CI 14%-50%); colorectal- 0% /9% (95% CI 0%-21%); endometrial 0%/13% (95% CI 1%-25%); ovarian 0%/3%(95% CI 0%-9%); and urinary tract 0%/3% (95% CI 0%-9%) cancer.

Conclusion: Neither colorectal, endometrial, ovarian nor urinary tract cancer was observed before 50 years of age. The point estimates for colorectal and endometrial cancers at age 75 were, however, higher than expected  despite undergoing regular surveillance . The patients examined were mostly selected from cancer kindreds, and the late onset cancers might not necessarily have been caused by the path_PMS2 variants. Clinical guidelines for monoallelic path_PMS2 carriers should be revised.