Impact of cell death pathway genes Fas 21377AA and FasL 2844CC polymorphisms on the risk of developing non-small cell lung cancer

Abstract

Background: The signalling pathway Fas and FasL system plays a  fundamental role in the regulation of apoptotic cell death and any disturbance of this pathway has been shown to promote immune escape
and tumorigenesis. Many types of cancers show reduced expression of FAS and elevated FasL expression. The Fas21377G/A, and FasL2844T/C polymorphisms might be associated with increased risk of lung cancer.

Objective: The interplay between genetic polymorphisms could participate in cancer development. This study aimed to examine the contribution of Fas21377AA and FasL2844CC genotypes to risk of developing lung cancer.

Subjects and methods: A case-control study was conducted on 20 non small cell lung cancer (NSCLC) cases and 40 controls. Genotyping of Fas 21377AA and FasL 2844CC Single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were done to all subjects.

Results: The distribution of Fas and FasL genotypes showed a higher frequency of Fas AA genotype among patients compared to controls with an increased risk of lung cancer (OR 5.28; CI:1.35–20.65, P value .01). No statistically significant difference was found between patients and controls groups in respect to FasL genotypes. Gene to gene interaction between Fas and FasL genotypes showed significant differences between the patients and controls groups. As regards the combination between FasL TT+CT & Fas AA, FasL CC & Fas GG+GA and FasL CC & Fas AA genotypes where patients carrying FasL CC or Fas AA genotypes have increased risk to develop lung cancer, (OR 10.28, 95% CI; 1.68–62.74, P value .01), (OR 72, 95% CI; 5.55–132.99, P value .001) and (OR 9, 95% CI; 1.5–53.86, P value .01) respectively. The FasL-CC genotype showed 2.25 folds increased risk to develop lung cancer in non-smoker patients, P = .008. No correlation was found between the pathological types, the stage of lung cancer and the Fas and FasL genotypes.

Conclusion: The interaction of the cell death pathwaygenes Fas and FasL polymorphisms could be associated with the risk of lung cancer, in the same respect Fas AA genotype could also potentiate this risk

Keywords: Cell death pathway genes Fas FasL polymorphisms Non small  cell lung cancer PCR-RFLP