Genetic Polymorphisms in Aquaporin 1 as Risk Factors for Malignant Mesothelioma and Biomarkers of Response to Cisplatin Treatment

BACKGROUND: Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. PATIENTS AND METHODS: The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. RESULTS: AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37–0.96, P(adj) = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27–0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27–0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00–4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01–9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00–8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00–13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13–19.05, P = 0.034) in additive model. CONCLUSIONS: AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.