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

Authors El-Hamamsy M, Ghali RR, Saad AS, Shaheen SM, Salem AM

Received 23 June 2016

Accepted for publication 8 September 2016

Published 7 November 2016 Volume 2016:9 Pages 6857—6863

DOI https://doi.org/10.2147/OTT.S115631

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza


Manal El-Hamamsy,1 Ramy R Ghali,2 Amr S Saad,2 Sara M Shaheen,1 Ahmed M Salem1

1Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; 2Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Background: FAS-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 methods: In 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.
Results: The 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).
Conclusion: The 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.

Keywords: mesothelioma, platinum, FAS, FAS ligand, genotyping, survival

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