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Article: Genetic predisposition to lung adenocarcinoma among never-smoking Chinese with different epidermal growth factor receptor mutation status

TitleGenetic predisposition to lung adenocarcinoma among never-smoking Chinese with different epidermal growth factor receptor mutation status
Authors
KeywordsEpidermal growth factor receptor mutation
Gene-environment interaction
Lung adenocarcinoma
Never-smokers
Single nucleotide polymorphisms
Issue Date2017
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/lungcan
Citation
Lung Cancer, 2017, v. 114, p. 79-89 How to Cite?
AbstractOBJECTIVES: The inconsistent findings from genetic association studies may be related to the heterogeneity in different molecular subtypes of lung cancer. This study evaluated the predisposing single-nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) mutant and EGFR wild-type lung adenocarcinoma separately among never-smokers. MATERIALS AND METHODS: This was a two-stage case-control study. Never-smokers with pathologically confirmed lung adenocarcinoma and healthy controls were recruited in Hong Kong and Macau. Genomic DNA was extracted and genotyped by MassARRAY. In the discovery stage, 51 SNPs were investigated at the SNP, gene and pathway level among 103 EGFR mutant and 78 EGFR wild-type lung adenocarcinoma cases compared with matched controls. In the validation stage, SNPs that were identified with significant lung cancer risk were replicated in a separate cohort of 84 lung adenocarcinoma cases and compared with 103 Chinese Han, Beijing and 105 Chinese Han, Southern public controls from the 1000 genome database. RESULTS AND CONCLUSION: The genetic association of IL-6 rs2069840 with EGFR mutant lung adenocarcinoma was ascertained. In the discovery stage, haplotype GGG in three SNPs (rs2069840, rs2069852, rs2066992) of IL-6, synergetic effects of IL-6 rs2069840 and environmental tobacco smoke in the workplace were found to be related to EGFR mutant lung adenocarcinoma. ERCC2 rs238406 showed a marginally significant association with EGFR mutant lung adenocarcinoma in the validation stage (P=0.096). ERCC2 rs50871 and ATM rs611646 showed significant association with EGFR wild-type lung adenocarcinoma in the discovery stage. In conclusion, IL-6 rs2069840 conferred susceptibility to EGFR mutant lung adenocarcinoma in a Hong Kong and Macau never-smoking Chinese population.
Persistent Identifierhttp://hdl.handle.net/10722/258650
ISSN
2017 Impact Factor: 4.486
2015 SCImago Journal Rankings: 1.923
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHan, L-
dc.contributor.authorLee, CK-
dc.contributor.authorPang, H-
dc.contributor.authorChan, HT-
dc.contributor.authorLo, IL-
dc.contributor.authorLam, SK-
dc.contributor.authorCheong, TH-
dc.contributor.authorHo, JCM-
dc.date.accessioned2018-08-22T01:41:50Z-
dc.date.available2018-08-22T01:41:50Z-
dc.date.issued2017-
dc.identifier.citationLung Cancer, 2017, v. 114, p. 79-89-
dc.identifier.issn0169-5002-
dc.identifier.urihttp://hdl.handle.net/10722/258650-
dc.description.abstractOBJECTIVES: The inconsistent findings from genetic association studies may be related to the heterogeneity in different molecular subtypes of lung cancer. This study evaluated the predisposing single-nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) mutant and EGFR wild-type lung adenocarcinoma separately among never-smokers. MATERIALS AND METHODS: This was a two-stage case-control study. Never-smokers with pathologically confirmed lung adenocarcinoma and healthy controls were recruited in Hong Kong and Macau. Genomic DNA was extracted and genotyped by MassARRAY. In the discovery stage, 51 SNPs were investigated at the SNP, gene and pathway level among 103 EGFR mutant and 78 EGFR wild-type lung adenocarcinoma cases compared with matched controls. In the validation stage, SNPs that were identified with significant lung cancer risk were replicated in a separate cohort of 84 lung adenocarcinoma cases and compared with 103 Chinese Han, Beijing and 105 Chinese Han, Southern public controls from the 1000 genome database. RESULTS AND CONCLUSION: The genetic association of IL-6 rs2069840 with EGFR mutant lung adenocarcinoma was ascertained. In the discovery stage, haplotype GGG in three SNPs (rs2069840, rs2069852, rs2066992) of IL-6, synergetic effects of IL-6 rs2069840 and environmental tobacco smoke in the workplace were found to be related to EGFR mutant lung adenocarcinoma. ERCC2 rs238406 showed a marginally significant association with EGFR mutant lung adenocarcinoma in the validation stage (P=0.096). ERCC2 rs50871 and ATM rs611646 showed significant association with EGFR wild-type lung adenocarcinoma in the discovery stage. In conclusion, IL-6 rs2069840 conferred susceptibility to EGFR mutant lung adenocarcinoma in a Hong Kong and Macau never-smoking Chinese population.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/lungcan-
dc.relation.ispartofLung Cancer-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEpidermal growth factor receptor mutation-
dc.subjectGene-environment interaction-
dc.subjectLung adenocarcinoma-
dc.subjectNever-smokers-
dc.subjectSingle nucleotide polymorphisms-
dc.titleGenetic predisposition to lung adenocarcinoma among never-smoking Chinese with different epidermal growth factor receptor mutation status-
dc.typeArticle-
dc.identifier.emailHo, JCM: jhocm@hku.hk-
dc.identifier.authorityHo, JCM=rp00258-
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.lungcan.2017.10.012-
dc.identifier.pmid29173771-
dc.identifier.hkuros287517-
dc.identifier.hkuros287782-
dc.identifier.volume114-
dc.identifier.spage79-
dc.identifier.epage89-
dc.identifier.isiWOS:000418782300013-
dc.publisher.placeIreland-

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