REV3L gene variants rs1002481, rs462779, and rs465646 lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir.

Abstract Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer accounting for 80–85% of all lung cancer cases. Various genetic studies have tried to reveal the association of REV3L (Protein reversion less 3-like) gene mutations with cancer, including lung cancer but no such study has been carried out in the population of Jammu and Kashmir (J&K).Methods: Four selected REV3L single nucleotide variants were genotyped using the TaqMan allele discrimination assay in 550 subjects (203 NSCLC patients and 347 healthy controls). The association of variants was evaluated by logistic regression.Results: Out of the four REV3L variants genotyped, we found rs1002481, rs462779, and rs465646 significantly associated with NSCLC risk with an Odds Ratio (OR) of 3.5 (1.98–6.3 at 95% CI ), p-value = 0.00002; OR = 4.4 (1.8–10.4 at 95% CI ), p-value = 0.00075; and OR = 2.4 (1.47–4.008 at 95% CI ), p-value = 0.00053, respectively. The analysis of rs465646/rs462779/rs1002481 haplotypic combinations revealed a significant association of AGT, AGA, GGT, and AAA haplotypes with NSCLC. Conclusion: The analysed data suggest a strong association of variants rs1002481, rs462779, rs465646 with NSCLC. This association is indicative of a potential role of mutations in the REV3L gene as risk factor for the development of NSCLC in the studied population. Although a first report from any Indian population, these variants have been previously reported to be associated with lung and colorectal cancers in different world populations. These data along with the analysed data supports the notation that these variants can be used as potential prognostic biomarker.