FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma

Abstract

BackgroundFAS-670 A>G (rs1800682) and FASL-844 C>T (rs763110) polymorphisms have been previously correlated with clinical outcome of non-small cell lung cancer (NSCLC) and breast and bladder cancers. We investigated the influence of these polymorphisms on clinical outcome of malignant pleural mesothelioma (MPM) patients.Patients and methodsIn this cohort study (NCT02269878), 68 epithelioid MPM Egyptian patients treated with first-line platinum-based chemotherapy were recruited in the period between April 2014 and May 2015. The genotype analysis was performed using TaqMan® single-nucleotide polymorphism genotyping assay. The association between the selected polymorphisms and response rate, progression-free survival (PFS) and overall survival (OS) at 18 months was evaluated.ResultsThe median age of patients was 55 years and 45.6% of them received platinum in combination with pemetrexed, while 54.4% received platinum in combination with gemcitabine. FASL-844 CC genotype was more common than expected in early-stage tumor (P=0.042). It was found that there was no association between the investigated polymorphisms and response rate or 18-month OS. However, the PFS rate at 18 months for FASL-844 CC genotype carriers was 45% versus 10.6% for FASL-844 CT/TT genotypes carriers (log-rank: 6.2; P=0.013). Also, the number of platinum-based cycles and tumor stage were found to be significant variables for PFS by univariate analysis (P≤0.001 and P=0.006, respectively). Stratified Cox regression showed that the carriers of FASL-844 CT/TT genotypes were still more susceptible to disease progression than carriers of FASL-844 CC genotype (adjusted HR =3.77, 95% CI: 1.34–10.62, P=0.012).ConclusionThe results of this study suggest that FASL-844 C/T polymorphism could predict PFS in MPM patients receiving platinum-based chemotherapy; therefore, this should be further evaluated as a potential marker for the prediction of clinical outcome in patients with MPM.

Genomic variants in Fas-mediated apoptosis pathway predict a poor response to Platinum-based Chemotherapy for Chinese Gastric Cancer Patients

“…Previous investigations demonstrated that those functional genetic variations of Fas/FasL/CASP8 may influence the susceptibility to gastric cancer or affected the sensitivity to platinum-based chemotherapy for some types of cancer, including non-small-cell lung cancer, malignant pleural mesothelioma and so on [29][30][31]. However, the associations between genomic variants involved in Fas-mediated apoptosis pathway, with the response to platinum-based chemotherapy for gastric cancer patients, was still unclear.…”

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

“… 22 FASL-844 polymorphism could predict progression free survival (PFS) in MM patients receiving platinum based chemotherapy. 23 Polymorphisms in REV1 and REV3L were also associated with the outcome of cisplatin based chemotherapy in MM. 24 The results of the study showed that DNA repair gene polymorphisms XRCC1 may modify the response to gemcitabine-platinum combination chemotherapy in MM patients.…”