Cancer Risk in Marfan Syndrome: A Swedish Population-Based Cohort Study.

Marfan syndrome is an autosomal dominant connective tissue disorder caused by pathogenic variants in the fibrillin-1-encoding gene. The cancer risk in Marfan syndrome is not fully understood, but recent reports have suggested an increased risk in adults. This study assessed cancer risk in Marfan syndrome using population-based data from the Swedish National registers. We performed a register-based nationwide matched cohort study of 1544 individuals with Marfan syndrome, born 1930-2017. Each individual was matched to 50 comparisons by birth year, sex and birth county. Cancer risk was estimated using Cox proportional hazard models, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). All cancer cases diagnosed before age 20 years were classified as childhood cancer, and those diagnosed at age 20 years or older were classified as adult cancer. The overall risk of adult cancer was not increased in individuals with Marfan syndrome (HR 1.00, 95% CI 0.78-1.27). However, there was an increased risk of endocrine tumours in adults with Marfan syndrome (HR 2.86, 95% CI 1.40-5.85). Furthermore, an over two-fold increased risk of cancer was observed among children with Marfan syndrome (HR 2.44, 95% CI 1.25-4.80). In this study, we found an increased cancer risk in children with Marfan syndrome. In contrast to previous reports, we did not detect an increased overall cancer risk in adults with Marfan syndrome, but an elevated site-specific risk of endocrine tumours. Further, larger studies are warranted to evaluate the lifetime cancer risk in Marfan syndrome at different ages.