title: FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma.
abstract: 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.
  
  
  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 andP=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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Manal
authors.initials: M
authors.lastname: El-Hamamsy
authors.affiliation: Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Ramy R
authors.initials: RR
authors.lastname: Ghali
authors.affiliation: Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Amr S
authors.initials: AS
authors.lastname: Saad
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Shaheen
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salem
keywords: FAS; FAS ligand; genotyping; mesothelioma; platinum; survival