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.

中文翻译：

---

鉴定转录因子E2F1的nsSNPs使个体易患肺癌和头颈癌。

E2Fs转录因子家族参与G1 / S过渡和DNA复制及其表达失调已在各种人类癌症中报道。研究表明，E2F1家族成员的遗传变异在头颈部癌变中起重要作用。在这项研究中，我们通过计算机分析预测了E2F1基因的六个高度有害的nsSNP（C227F，R252H，V295D，C298Y，R56W和Y59C）。后者基于蛋白质的结构，功能和氨基酸保守性。分子动力学研究表明突变蛋白的结构与总体蛋白参数存在偏差。进一步，进行了一项包括535个样本（305个癌症患者和230个对照）的病例对照研究，以发现预测的SNP与肺癌（LC）和头颈癌（HNC）的易感性之间的关系。使用内部人工RFLP方法进行基因分型。统计分析表明，在所有遗传模型中，rs3213172（R252H）的突变等位基因/基因型增加了LC和HNC的2-5倍风险。这些结果表明，E2F1基因的rs3213172C / T多态性可以用作对人群中LC和HNC遗传易感性的有效生物标记。统计分析表明，在所有遗传模型中，rs3213172（R252H）的突变等位基因/基因型增加了LC和HNC的2-5倍风险。这些结果表明，E2F1基因的rs3213172C / T多态性可以用作对人群中LC和HNC遗传易感性的有效生物标记。统计分析表明，在所有遗传模型中，rs3213172（R252H）的突变等位基因/基因型增加了LC和HNC的2-5倍风险。这些结果表明，E2F1基因的rs3213172C / T多态性可以用作对人群中LC和HNC遗传易感性的有效生物标记。