Singh S, et al. Mutat Res 2020.
E2Fs transcription factors family is involved in the G1/S transition and DNA replication and their deregulated expression have been reported in various human cancers. Studies have shown that the genetic variants of E2F1 family members play an important role in head and neck carcinogenesis. In this study, we predicted six highly deleterious nsSNPs (C227F, R252H, V295D, C298Y, R56W, and Y59C) of E2F1 gene through in silico analyses. The latter was based on protein structure, function, and amino
acid conservation. Molecular dynamics studies showed a deviation of the structures of the mutant proteins from the global protein parameters. Further, a case-control study that included total 535 samples (305 cancer patients and 230 controls) was conducted to find the association of the predicted SNPs with the susceptibility to lung cancer (LC) and head and neck cancer (HNC). The genotyping was done applying in-house artificial-RFLP method. Statistical analysis showed that the mutant alleles/genotypes of rs3213172 (R252H) were found to increase ∼ 2-5 fold risk of LC and HNC in all the genetic models. These results suggest that the rs3213172C/T polymorphism of the E2F1 gene could be used as an effective biomarker for genetic susceptibility to LC and HNC in our population.