A missense variant of MASP2 is associated with increased risk of radiation pneumonitis in lung cancer patients treated with radiation therapy*

Abstract

Abstract Objective In this study, mannan-binding lectin-associated serine protease 2 (MASP2) gene variant was evaluated to assess the risk of radiation pneumonitis (RP) in patients with pulmonary malignancies. Methods A total of 169 lung cancer patients with radiotherapy were included in our prospective study (NCT02490319) and genotyped using the Sanger sequencing method. Multivariate Cox hazards analysis and multiple testing were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly associated with RP risk. Results Patients with mean lung disease ≥ 15 Gy and V20 ≥ 24% had higher risk of RP ≥ grade 2 compared with their counterparts (HR = 1.888, 95% CI: 1.186-3.004, P = 0.007; HR = 2.126, 95% CI: 1.338-3.378, P = 0.001, respectively). Importantly, CC + CA genotype of MASP2: rs12711521 was strongly associated with an increased occurrence of RP ≥ grade 2 (HR = 1.949, 95% CI: 1.278-2.971, P = 0.002). Conclusion MASP2: rs12711521 was found to be significantly associated with RP ≥ grade 2 in our cohort and may thus be one of the important predictors of severe RP before radiotherapy, if further validated in larger population.