Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Radiol Oncol. 2019 Mar 3;53(1):96-104. doi: 10.2478/raon-2019-0009.
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, Padj = 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.
恶性间皮瘤（MM）是一种与石棉有关的侵袭性肿瘤，预后较差。本研究旨在探讨水通道蛋白 1（AQP1）基因多态性是否影响 MM 的发病风险和顺铂为基础的 MM 治疗反应。
这项病例对照研究纳入了 231 名 MM 患者和 316 名健康献血者作为对照组。所有受试者均对三个 AQP1 多态性（rs1049305、rs1476597 和 rs28362731）进行了基因分型。采用 logistic 和 Cox 回归进行统计分析。
AQP1 rs1049305 多态性在调整性别和年龄的优势模型中与 MM 风险显著相关（OR = 0.60，95%CI = 0.37-0.96，Padj = 0.033）。该多态性也与基于顺铂的治疗相关性贫血显著相关（未经调整：OR = 0.49，95%CI = 0.27-0.90，P = 0.021；调整 CRP：OR = 0.52，95%CI = 0.27-0.99，P = 0.046），优势模型中与白细胞减少症（OR = 2.09，95%CI = 1.00-4.35，P = 0.049），与血小板减少症（OR = 3.06，95%CI = 1.01-9.28，P = 0.048）和脱发（OR = 2.92，95%CI = 1.00-8.46，P = 0.049）显著相关。AQP1 rs28362731 与血小板减少症显著相关（未经调整：OR = 3.73，95%CI = 1.00-13.84，P = 0.049；调整疼痛：OR = 4.63，95%CI = 1.13-19.05，P = 0.034），在加性模型中。
AQP1 可能在 MM 的发病风险中起作用。此外，AQP1 基因型信息可以提高对顺铂毒性风险增加的 MM 患者的预测能力。
