REV3L single nucleotide variants lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir

Background: Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for 80-85% of all lung cancer cases. Various genetic studies have associated REV3L (Protein reversion less 3-like) gene mutations, which encodes the catalytic subunit of error prone translesion synthesis polymerase zeta with cancer, including lung cancer; however, no such data is available from any North Indian population. In this study we attempted to screen the North Indian population of Jammu and Kashmir (J&K) for the potential role of REV3L gene polymorphisms in NSCLC. Methods: A total of four REV3L single nucleotide variants were selected for genotyping based on the available literature. The genotyping was carried out by using the TaqMan allele discrimination assay in 500 subjects (200 NSCLC patients and 300 age and sex matched healthy controls). The association of variants with NSCLC was evaluated by logistic regression. Results: Out of the four REV3L variants genotyped; rs1002481, rs462779, and rs465646 were found significantly associated with NSCLC risk under the recessive model, with an Odds Ratio (OR) of 3.52(2.14-5.8 at 95% CI, pvalue = 0.00000062), 3.7 (1.8-7.6 at 95% CI, p-value = 0.00031), and 2.2 (1.47-3.37 at 95% CI, p-value = 0.0003), respectively. Discussion: Our data supports a strong association between variants rs1002481, rs462779, rs465646 and NSCLC, indicating a potential role of these REV3L variants in increasing the risk 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. Our data along with the existing data supports the notation that these variants can be used as potential genetic predisposition markers. Availability of data and materials: Data generated and analysed during study is not available publicly but can be made available from the corresponding author upon reasonable request.

Automated summary

This study identified a significant association between REV3L gene polymorphisms and the risk of non-small cell lung cancer (NSCLC) in the North Indian population, suggesting a potential role of these variants in increasing the risk for NSCLC development. These findings support the use of these variants as potential genetic predisposition markers for NSCLC.