BACKGROUND/AIM: The associations between the polymorphisms in the promoter region of the V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) gene and lung cancer risk were investigated. MATERIALS AND METHODS: By direct sequencing, we first found two known polymorphisms (-536 A/G and -276 C/T). Further TaqMan assays and logistic regression analyses were performed in order to characterize the association between the -276 C/T polymorphism of ERBB3 and lung cancer risk in 425 patients with lung cancer and 411 healthy controls. To examine the potential effects of the -276 C/T polymorphism on ERBB3 transcription, luciferase reporter assays were performed in non-small cell lung cancer (NSCLC) cell lines. RESULTS: The -276 C/T polymorphism was associated with the risk of lung cancer in a recessive model of never-smokers. Interestingly, the T allele conferred significantly lower promoter activity by 32% and 33% than the C allele in H2009 and H358 cell lines. CONCLUSION: ERBB3 promoter polymorphisms affect ERBB3 gene expression, and contribute to genetic susceptibility to lung cancer in never-smokers.
BACKGROUND/AIM: The associations between the polymorphisms in the promoter region of the V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) gene and lung cancer risk were investigated. MATERIALS AND METHODS: By direct sequencing, we first found two known polymorphisms (-536 A/G and -276 C/T). Further TaqMan assays and logistic regression analyses were performed in order to characterize the association between the -276 C/T polymorphism of ERBB3 and lung cancer risk in 425 patients with lung cancer and 411 healthy controls. To examine the potential effects of the -276 C/T polymorphism on ERBB3 transcription, luciferase reporter assays were performed in non-small cell lung cancer (NSCLC) cell lines. RESULTS: The -276 C/T polymorphism was associated with the risk of lung cancer in a recessive model of never-smokers. Interestingly, the T allele conferred significantly lower promoter activity by 32% and 33% than the C allele in H2009 and H358 cell lines. CONCLUSION:ERBB3 promoter polymorphisms affect ERBB3 gene expression, and contribute to genetic susceptibility to lung cancer in never-smokers.
Authors: Aideen M McInerney-Leo; Hui Yi Chew; Po-Ling Inglis; Paul J Leo; Shannon R Joseph; Caroline L Cooper; Satomi Okano; Tim Hassall; Lisa K Anderson; Rayleen V Bowman; Michael Gattas; Jessica E Harris; Mhairi S Marshall; Janet G Shaw; Lawrie Wheeler; Ian A Yang; Matthew A Brown; Kwun M Fong; Fiona Simpson; Emma L Duncan Journal: Hum Mol Genet Date: 2021-11-30 Impact factor: 6.150