Bhat Gh Rasool, Verma Sonali, Bhat Amrita, Shah Ruchi, Sethi Itty, Dar Khursheed A, Abrol Deepak, Bhat Audesh, Raina Rakesh, Kumar Rakesh
Cancer Genetics Research Group, ICMR, Centre for Advanced Research, School of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K UT India.
Human Genetics Research Group, School of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K UT India.
3 Biotech. 2020 Sep;10(9):410. doi: 10.1007/s13205-020-02403-1. Epub 2020 Aug 28.
Various Genome-wide association studies (GWAS) have reported the association of variant rs2494938 with lung cancer. However, genetic association of genetic variation with non-small cell lung cancer (NSCLC) in North Indian population remained unexplored. We conducted a case-control association study using TaqMan-based chemistry in which a total of 619 individuals, 189 NSCLC cases and 430 controls, were genotyped to explore the association of rs2494938 genetic variant of the gene with NSCLC patients from North India. The allele 'G' (risk allele) of the genetic variant rs2494938 was significantly associated with the NSCLC [OR = 1.51 (1.18-1.93 at 95% CI); value = 0.0009]. Genetic association was also explored by applying different genetic models (Dominant, Additive). These results suggest that rs2494938 polymorphism of the gene is a risk factor in the North Indian populations to develop NSCLC. The LD (Linkage Disequilibrium) plot demonstrates the variant and its LD SNPs ( > 0.8) and the variant has direct regulatory effect, which could affect the overall physiology of the gene. These findings could be used as diagnostic and prognostic markers in clinical studies of lung cancer patients in North Indian population groups. The present study also provides an important evidence on the genetic etiology of NSCLC in North Indian populations and further expounds GWAS findings on the role of in lung cancer risk. This study provides the holistic view about the non-small cell lung cancer in Jammu and Kashmir, North Indian population and it can be a hallmark of cancer if verified on a very large sample size (cohort).
多项全基因组关联研究（GWAS）报告了基因变异rs2494938与肺癌的关联。然而，在北印度人群中，该基因变异与非小细胞肺癌（NSCLC）的遗传关联仍未得到探索。我们采用基于TaqMan技术的方法进行了一项病例对照关联研究，对总共619名个体（189例NSCLC患者和430名对照）进行基因分型，以探究该基因的rs2494938基因变异与来自北印度的NSCLC患者之间的关联。基因变异rs2494938的等位基因“G”（风险等位基因）与NSCLC显著相关[比值比（OR）=1.51（95%置信区间为1.18 - 1.93）；P值 = 0.0009]。还通过应用不同的遗传模型（显性、加性）来探究遗传关联。这些结果表明，该基因的rs2494938多态性是北印度人群发生NSCLC的一个风险因素。连锁不平衡（LD）图展示了该变异及其LD单核苷酸多态性（r²>0.8），并且该变异具有直接调控作用，这可能会影响该基因的整体生理学功能。这些发现可作为北印度人群肺癌患者临床研究中的诊断和预后标志物。本研究还为北印度人群中NSCLC的遗传病因提供了重要证据，并进一步阐述了GWAS关于该基因在肺癌风险中作用的研究结果。本研究提供了关于北印度查谟和克什米尔地区非小细胞肺癌的整体观点，如果在非常大的样本量（队列）上得到验证，它可能成为癌症研究的一个标志。
