Association between malignancies and Marfan syndrome: a population-based, nested case-control study in Taiwan

Abstract

Objective: Marfan syndrome (MFS) involves a deficiency of the structural extracellular matrix component fibrillin-1 and overactivation of the transforming growth factor-β (TGF-β) signalling pathway. The TGF-β signalling pathway also actively participates in malignant transformation. Although anecdotal case reports have suggested associations between MFS/MFS-like conditions and several haematological and solid malignancies, such associations have not been thoroughly evaluated in large-scale studies. We sought to use a nationwide healthcare insurance claim database to evaluate whether patients with MFS are at increased risk of malignancy.

Patients and methods: We conducted a nested case-control analysis using a database extracted from Taiwan's National Health Insurance Research Database. All medical conditions for each case and control were categorised using the International Classification of Diseases, 9th Revision classifications. ORs and 95% CIs for associations between MFS and malignancies were estimated using conditional logistic regression and adjusted for comorbidities.

Results: Our analyses included 1 153 137 cancer cases and 1 153 137 propensity score-matched controls. Relative to other subjects, patients with MFS had a significantly higher risk of having a malignancy (adjusted OR 3.991) and hypertension (adjusted OR 1.964) and were significantly more likely to be men. Malignancies originating from the head and neck and the urinary tract were significantly more frequent among patients with MFS than among subjects without MFS.

Conclusion: Patients with MFS are at increased risk of developing various malignancies. Healthcare professionals should be aware of this risk when treating such patients, and increased cancer surveillance may be necessary for these patients.

Keywords: fibrillin; malignancy; marfan syndrome; transforming growth factor-β.

Figure 1

Patient selection flow chart.