The single nucleotide variant rs2868371 associates with the risk of mortality in non-small cell lung cancer patients: A multicenter prospective validation.
Radiother Oncol
; 136: 29-36, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31015126
ABSTRACT
BACKGROUND AND PURPOSE:
Definitive radiation therapy (RT) with or without chemotherapy has become the standard treatment for non-metastatic unresectable non-small cell lung cancer (NSCLC). However, treatment outcomes can differ substantially and patients' genetic background could play a crucial role. Potential associations between single-nucleotide polymorphisms (SNP) in Heat shock protein beta-1 (HSPB1) and survival have been reported in prior single-institution retrospective reports. MATERIALS ANDMETHODS:
The current assay aims to validate such connection in a prospective multicenter study in a European cohort including 181 NSCLC patients. Median follow-up time for all patients was 13â¯months (range, 3-57â¯months).RESULTS:
The results obtained show an association between the rs2868371 GG genotype and better overall survival (HR 0.35; 95%CI 0.13-0.96; pâ¯=â¯0.042) in multivariate analysis. Two-year overall survival rate was 72% for patients carrying the rs2868371 GG genotype versus 36% for those patients harboring the rs2868371 CC/CG genotypes (pâ¯=â¯0.013). Additionally, the rs2868371 GG genotype was found to be associated with better disease-free survival in the multivariate analysis (HR 0.36; 95%CI 0.13-0.99; pâ¯=â¯0.048). In silico analysis of the potential functional SNP suggested significant difference in the affinity of the Glucocorticoid Receptor binding site between alternative allelic variants, confirmed by chromatin immunoprecipitation analysis displaying stronger affinity for the risk allele (C). Furthermore, our findings indicate that the rs2868371 influences (mRNA) HSPB1 expression, offering insight into the regulation of HSPB1 transcription.CONCLUSION:
The functional HSPB1 rs2868371 promoter variant may affect lung cancer survival by regulation of HSPB1 expression levels through glucocorticoid receptor interaction.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Chaperonas Moleculares
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Proteínas de Choque Térmico
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Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2019
Tipo de documento:
Article