Scientific Reports: A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups (Bishop Lab)

Published On: July 19, 2021
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  • Debmalya Sengupta,
  • Souradeep Banerjee,
  • Pramiti Mukhopadhyay (Bishop Lab) 
  • Ritabrata Mitra,
  • Tamohan Chaudhuri,
  • Abhijit Sarkar,
  • Gautam Bhattacharjee,
  • Somsubhra Nath,
  • Susanta Roychoudhury,
  • Samsiddhi Bhattacharjee &
  • Mainak Sengupta

Abstract

Reports of genetic association of polymorphisms with lung cancer in the Indian subcontinent are often conflicting. To summarise and replicate published evidence for association with lung cancer and its subgroups. We performed a meta-analysis of candidate associations on lung cancer, its histological subtypes, and smoking status in the Indian subcontinent following PRISMA guidelines. Multiple testing corrections were done by the Benjamini–Hochberg method through assessment of significance at a false discovery rate of 10%. We genotyped and investigated rs1048943/CYP1A1 in a case-control sample from eastern India, followed by its global meta-analysis using a similar protocol. Meta-analysis of 18 variants of 11 genes reported in 39 studies (7630 cases and 8169 controls) showed a significant association of rs1048943/CYP1A1 [2.07(1.49–2.87)] and rs4646903/CYP1A1 [1.48(1.93–1.95)] with overall lung cancer risk at 10% FDR, while nominal association (p < 0.05) was observed for del1/GSTT1, del2/GSTM1, rs1695/GSTP1, and rs17037102/ DKK2. Subtype analysis showed a significant association of del1/GSTT1 with adenocarcinoma, rs4646903/CYP1A1 with squamous carcinoma, and rs1048943/CYP1A1 with both. Association of rs4646903/CYP1A1 in smokers and effect modification by meta-regression analysis was observed. Genotyping of rs1048943/CYP1A1 that presented significant heterogeneity (p < 0.1) revealed an association with adenocarcinoma among eastern Indian smokers, while a global meta-analysis in 10458 cases and 10871 controls showed association with lung cancer and its subgroups. This study identified the susceptibility loci for lung cancer and its covariate-subgroups.

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Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to the understanding of its causes, and accelerate the translation of knowledge into novel therapies. Through discovery, development, and dissemination of new scientific knowledge, Greehey CCRI strives to have a national and global impact on childhood cancer. Our mission consists of three key areas — research, clinical, and education.

Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.

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Article Categories: Research Paper

Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.