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
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]