Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment

Our plain-English summary of Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment, by B. Senk, K. Goricar, V. Kovac, et al (Radiology and Oncology, 2019).

The study

• Authors: B. Senk, K. Goricar, V. Kovac, V. Dolzan, A. Franko
• Journal: Radiology and Oncology
• Published: 2019;53(1):96-104
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This Slovenian case-control study examined whether aquaporin 1 (AQP1) gene variants were linked to mesothelioma risk and cisplatin treatment outcomes. It compared 231 patients, mostly with pleural and some with peritoneal mesothelioma, treated in Ljubljana from 2007 to 2016, with 316 healthy blood donors. Asbestos exposure was confirmed in 166 patients (73.8% of those with information). Controls had no asbestos information. Of three variants tested, one was excluded after failing a genetic consistency check. Without adjustment, no variant was linked to mesothelioma risk. After adjustment for age and gender, carriers of at least one C copy of rs1049305 had lower odds of mesothelioma (OR 0.60, 95% CI 0.37 to 0.96). Among cisplatin-treated patients, neither remaining variant was significantly associated with survival or tumour response. rs1049305 C carriers had lower odds of grade 2 or higher anaemia and higher odds of grade 2 or higher low white cell counts. Its CC genotype was linked to hair loss, and to low platelets only before adjustment for pain. rs28362731 was linked only to low platelets. The authors concluded that AQP1 may play a role in mesothelioma risk and cisplatin toxicity, pending confirmation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case-control genetic association study, with an analysis of treatment outcomes and side effects among the patients
• Who was studied: 231 patients treated mostly for pleural, and some for peritoneal, malignant mesothelioma at the Institute of Oncology Ljubljana, Slovenia, from 2007 to the end of 2016. Their median age was 66, 73.6% were men, and 194 received cisplatin-based chemotherapy. Controls were 316 healthy blood donors over 40 years old (235 men, 81 women; median age 49).
• Exposure: Three AQP1 gene variants (rs1049305, rs1476597, rs28362731), and cisplatin-based chemotherapy (gemcitabine/cisplatin or pemetrexed/cisplatin). Asbestos exposure was confirmed in 166 patients (73.8%), a percentage of patients with exposure information; exposure data were missing for 6 patients. No fiber types were specified, and controls had no asbestos exposure information.
• Main results:
  • The rs1476597 variant was excluded from further analysis because its genotype distribution in both patients and controls was not consistent with Hardy-Weinberg equilibrium.
  • rs1049305 was associated with mesothelioma risk only after adjustment for gender and age. Carriers of at least one C allele (GC+CC), compared with GG, had OR = 0.60, 95% CI = 0.37–0.96, adjusted P = 0.033 (dominant model).
  • rs28362731 was not significantly associated with the risk of developing mesothelioma.
  • Among cisplatin-treated patients, neither rs1049305 nor rs28362731 was significantly associated with progression-free survival, overall survival or response rate.
  • rs1049305 C allele carriers (GC+CC, dominant model) had lower odds of anaemia grade 2 or higher during cisplatin-based treatment. 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.
  • rs1049305 was associated with leukopenia grade 2 or higher. For the CC genotype (additive model): OR = 3.03, 95% CI = 1.10–8.38, P = 0.033. For C allele carriers (dominant model): OR = 2.09, 95% CI = 1.00–4.35, P = 0.049.
  • The rs1049305 CC genotype was associated with thrombocytopenia in the additive model before adjustment (OR = 3.06, 95% CI = 1.01–9.28, P = 0.048), but not in the dominant model. Table 5 shows the CC association was not significant after adjustment for pain at diagnosis (OR = 2.18, 95% CI 0.69–6.94, P = 0.185).
  • The rs1049305 CC genotype was associated with alopecia (OR = 2.92, 95% CI = 1.00–8.46, P = 0.049). This variant was not associated with neutropenia, nephrotoxicity or nausea and/or vomiting.
  • The rs28362731 GA genotype was associated only with thrombocytopenia. Unadjusted: OR = 3.73, 95% CI = 1.00–13.84, P = 0.049. Adjusted for pain at diagnosis: OR = 4.63, 95% CI = 1.13–19.05, P = 0.034.
  • Side effects were not influenced by interactions between either studied variant and smoking.
• The authors' conclusion: The authors concluded that AQP1 may play a role in the risk of malignant mesothelioma. They also concluded that AQP1 genotype information could improve prediction of which patients are at increased risk of cisplatin toxicity.
• Limitations the authors state:
  • There was no information on asbestos exposure in the healthy controls (described by the authors as the major limitation).
  • Patients were older than controls, because blood donors can only be up to 65 years old. The authors adjusted for age in the analysis.
  • The number of patients was limited.
  • The findings need to be validated in independent patient cohorts and in other cancers.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Biomarker, Cisplatin, Prognosis, Case-Control Study.

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