Delineating the cancer risks of MSH6 mutation carriers – preliminary results with simple statistics

Anne-Sophie van der Werf – ‘t Lam 1, Fonnet Bleeker 2, Encarna Gomez-García 3, Liselot van Hest 4, Mirjam de Jong 5, Tom Letteboer 6, Theo van Os 7, Liesbeth Spruijt 8, Anja Wagner 9, Maartje Nielsen 10

1 Leiden University Medical Center, Leiden, Netherlands. 2 Familial Cancer Clinic, Netherlands Cancer Institute, Amsterdam, Netherlands. 3 Maastricht University Medical Center, Maastricht, Netherlands. 4 Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 5 University Medical Center Groningen, Groningen, Netherlands. 6 University Medical Center, Utrecht, Netherlands. 7 Academic Medical Center, Amsterdam, Netherlands. 8 Radboud University Medical Center, Nijmegen, Netherlands. 9 Erasmus University Medical Center, Rotterdam, Netherlands. 10 Leiden University Medical Center, Leidenl, Netherlands



Cancer risks for MSH6 mutation carriers are different compared to MLH1/MSH2 mutation carriers. This will be emphasised since universal tumour screening for mismatch repair is recently introduced and panel testing is more common practice. This poses challenges in counselling patients. Therefore our aim is to describe the colonic and extracolonic cancer risks of MSH6 mutation carriers in the Netherlands. As this is an ongoing study, we would like to present the preliminary results.


Coded family pedigrees will be collected of all MSH6 families in the Netherlands in whom a pathogenic mutation was detected from 1995 until June 2019. Counselled patients were contacted through the clinical genetics department for informed consent to request their medical data. Cumulative cancer risks will be calculated in proven pathogenic MSH6 mutation carriers with Kaplan Meier curves in SPSS Statistics 23. Missing ages will be imputed with the mean of ages of that specific cancer.


In total 300 families were included on 04-06-2019 accountable for 13.828 family members of which 1193 proven mutation carriers. Cumulative risk at age 70 are for colorectal cancer 45.6% (95%CI: 42.8-48.4%) and for endometrium carcinoma 54.8% (95%CI: 51.3-58.3%).


These results are most likely an overestimation of the true cancer risk because there was no correction for ascertainment bias. Cancer risk analysis for urinary tract cancer, breast and ovarian cancer is ongoing.  As this is an ongoing study more families will be added for the final analysis and there will be a correction for ascertainment bias.