Cancer Genetics Research Group, ICMR, Centre for Advanced Research, School of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K UT, India.
Department of Obstetrics and Gynecology, Government Medical College Srinagar, Srinagar, India.
Sci Rep. 2021 May 28;11(1):11291. doi: 10.1038/s41598-021-90742-1.
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.
肺癌在遗传上具有多样性，是一个主要的健康负担。非小细胞肺癌（NSCLC）占肺癌总病例的 80%，20%的病例为小细胞肺癌（SCLC）。本病例对照关联研究侧重于使用安捷伦 MassARRAY 基质辅助激光解吸/电离飞行时间、质谱（MALDI-TOF）平台进行高通量基因分型，以分析候选遗传变异的遗传关联，该平台具有成本效益。我们在 723 个样本（162 个 NSCLC 病例和 592 个健康对照）中进行了多重 PCR 和 12 个单核苷酸多态性（SNP）的基因分型。这些遗传变异是从文献中选择的，因为它们与全球各种癌症有关，这是该地区首次研究这些至关重要的遗传变异。采用前瞻性病例对照关联研究设计，评估了来自 10 个基因的 12 个变体。在这 12 个变体中，TCF21（rs12190287）、ERCC1（rs2298881、11615）、ERCC5（rs751402）、ARNTL（rs4757151）、BRIP1（rs4986764）在查谟和克什米尔人群中与 NSCLC 风险显著相关（p≤0.003）。这些遗传变异的计算机模拟研究结果表明了其具有显著的功能作用，需要进行体外验证。进一步预计，这种病例对照研究将帮助我们了解非小细胞肺癌的遗传缺失。
