Genetic evaluation of the variants using MassARRAY in non-small cell lung cancer among North Indians

Gh Rasool Bhat,Deepak Abrol,Sonali Verma,Muddasser Nazir,Itty Sethi,Rakesh Kumar,Ruchi Shah,Khursheed A Dar,Amrita Bhat,Bhanu Sharma,Divya Bakshi

doi:10.1038/s41598-021-90742-1

Abstract

Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). The present case–control association study focused on the cost effective high throughput genotyping using Agena MassARRAY matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) platform to analyze the genetic association of candidate genetic variants. We performed multiplex PCR and genotyped twelve single nucleotide polymorphisms (SNPs) in 723 samples (162 NSCLC cases and 592 healthy controls). These genetic variants were selected from literature for their association with various cancers worldwide and this is the first study from the region to examine these critically important genetic variants. With prospective case–control association study design, twelve variants from ten genes were evaluated. Amongst these six variants, TCF21 (rs12190287), ERCC1 (rs2298881, 11615), ERCC5 (rs751402), ARNTL (rs4757151), BRIP1 (rs4986764) showed significant association with NSCLC risk (p ≤ 0.003) in Jammu and Kashmir population. In-silico findings of these genetic variants showed remarkable functional roles that needs in-vitro validations. It is further anticipated that such case control studies will help us in understanding the missing heritability of non-small cell lung cancer.

Highlights

Lung cancer is genetically diverse and a major health burden
The population enrolled in this study was genotyped for twelve genetic variants of ten genes including Transcription factor 21 (TCF21), Excision repair cross complimentary group-1 (ERCC1), ERCC5, ARNTL, BRIP1, REV1, PIK3CA, Cancer Susceptibility Candidate 16 gene (CASC16), DDC and BCL2 as mentioned in Supplementary Table 1
The allele (C) of variant rs4757151 (C/G) exhibited significant association with Non-small cell lung cancer (NSCLC) risk with an odds ratio (OR) of 2.12 (1.32–3.47 at 95% of CI) and p value of 0.002 (Table 2). This variant has not been evaluated for the non-small cell lung cancer risk in any Indian population group and our results proved that rs4757151 of ARNTL is a risk factor for NSCLC in Jammu and Kashmir (J&K) population, North India

Summary

Introduction

Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). Genetic characterization of variants have attracted significant attention in current medical era as potential biomarkers for predicting disease susceptibility and therapeutic targets[8] With this background, the variants in genes, which are critically important in various biological pathways like DNA damage and repair, invasion, metastasis, autophagy, circadian rhythm, apoptosis and signaling processes like TCF21, ERCC1, BRIP1, ARNTL, ERCC5, REV1, PIK3CA, CASC16, DDC, BCL2 were targeted. It is noteworthy that such studies will provide the holistic view of genetic landscape of non-small cell lung cancer in population of Jammu and Kashmir, North India With this perspective, we evaluated twelve genetic variants of ten genes that are critically important and were previously associated with various cancers including lung cancer.

Methods

Results

Conclusion