A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups

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 his...

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Autores principales:	Debmalya Sengupta, Souradeep Banerjee, Pramiti Mukhopadhyay, Ritabrata Mitra, Tamohan Chaudhuri, Abhijit Sarkar, Gautam Bhattacharjee, Somsubhra Nath, Susanta Roychoudhury, Samsiddhi Bhattacharjee, Mainak Sengupta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b9489cf02884b0bbf68a67c6b4e1fca
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spelling	oai:doaj.org-article:9b9489cf02884b0bbf68a67c6b4e1fca2021-12-02T15:33:13ZA comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups10.1038/s41598-021-92275-z2045-2322https://doaj.org/article/9b9489cf02884b0bbf68a67c6b4e1fca2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92275-zhttps://doaj.org/toc/2045-2322Abstract 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 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.Debmalya SenguptaSouradeep BanerjeePramiti MukhopadhyayRitabrata MitraTamohan ChaudhuriAbhijit SarkarGautam BhattacharjeeSomsubhra NathSusanta RoychoudhurySamsiddhi BhattacharjeeMainak SenguptaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debmalya Sengupta Souradeep Banerjee Pramiti Mukhopadhyay Ritabrata Mitra Tamohan Chaudhuri Abhijit Sarkar Gautam Bhattacharjee Somsubhra Nath Susanta Roychoudhury Samsiddhi Bhattacharjee Mainak Sengupta A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
description	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 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.
format	article
author	Debmalya Sengupta Souradeep Banerjee Pramiti Mukhopadhyay Ritabrata Mitra Tamohan Chaudhuri Abhijit Sarkar Gautam Bhattacharjee Somsubhra Nath Susanta Roychoudhury Samsiddhi Bhattacharjee Mainak Sengupta
author_facet	Debmalya Sengupta Souradeep Banerjee Pramiti Mukhopadhyay Ritabrata Mitra Tamohan Chaudhuri Abhijit Sarkar Gautam Bhattacharjee Somsubhra Nath Susanta Roychoudhury Samsiddhi Bhattacharjee Mainak Sengupta
author_sort	Debmalya Sengupta
title	A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
title_short	A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
title_full	A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
title_fullStr	A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
title_full_unstemmed	A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
title_sort	comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b9489cf02884b0bbf68a67c6b4e1fca
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A comprehensive meta-analysis and a case–control study give insights into genetic susceptibility of lung cancer and subgroups

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