TERT Polymorphism rs2736100-C Is Associated with EGFR Mutation-Positive Non-Small Cell Lung Cancer.
Clin Cancer Res
; 21(22): 5173-5180, 2015 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-26149460
ABSTRACT
PURPOSE:
EGF receptor (EGFR) mutation-positive (EGFRmut(+)) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, for example, adenocarcinoma histology, never-smoking history, and female gender. We aim to test the association between TERT polymorphism and EGFRmut(+) NSCLC. EXPERIMENTALDESIGN:
We conducted a genetic association study in Chinese patients with NSCLC (n = 714) and healthy controls (n = 2,520), between the rs2736100 polymorphism and EGFRmut(+) NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored.RESULTS:
The rs2736100-C allele was significantly associated with EGFRmut(+) NSCLC [OR, 1.52; 95% confidence interval (CI), 1.28-1.80; P = 1.6 × 10(-6)] but not EGFRmut(-) NSCLC (OR = 1.07, 95% CI, 0.92-1.24, P = 0.4). While patients with NSCLC as a whole have significantly longer LTL than healthy controls (P ≤ 10(-13)), the EGFRmut(+) patients have even longer LTL than EGFRmut(-) patients (P = 0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status, and histology (P < 0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro.CONCLUSIONS:
Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut(+) NSCLC. Further investigation for the underlying mechanism is warranted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Telomerase
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Estudos de Associação Genética
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Receptores ErbB
Tipo de estudo:
Etiology_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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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA