Genetic polymorphism in EGF is associated with prostate cancer aggressiveness and progression-free interval in androgen blockade-treated patients

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Ana L Teixeira (Autor) Outra; Ricardo Ribeiro (Autor) Outra; Diana Cardoso (Autor) Outra; Daniela Pinto (Autor) Outra; Francisco Lobo (Autor) Outra; Avelino Fraga (Autor) Outra; Francisco Pina (Autor) Outra; Fernando Calais da Silva (Autor) Outra; Rui Medeiros (Autor) ICBAS

Revista

Título: Clinical Cancer Research

Vol. 14

Páginas: 3367-3371

ISSN: 1078-0432

Editora: American Association for Cancer Research

Indexação

ISI Web of Knowledge - 32 Citações

Scopus - 34 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-003-YP8

DOI: 10.1158/1078-0432.ccr-07-5119

Abstract (EN): Purpose: Most prostate cancer patients develop resistance to androgen deprivation treatment, resulting in hormone resistance. Epidermal growth factor (EGF) activates several pro-oncogenic intracellular pathways inducing proliferation, differentiation, and tumorigenesis in epithelial cells. The EGF-EGF receptor pathway seems to be especially relevant in hormone-resistant prostate cancer stage. A single nucleotide polymorphism G>A in +61 locus of EGF gene has been described, in which A homozygous carriers express significantly less EGF protein compared with G allele carriers. Our purpose was to investigate the potential prognostic and predictive role of EGF functional genetic variant +61G>A in prostate cancer patients submitted to androgen blockade therapy (ABT). Experimental Design: We conducted a case-control study in prostate cancer patients treated with ABT (n = 123) and in healthy controls without evidence of cancer (n = 152). Cumulatively, a follow-up study (median follow-up, 37 months) was undertaken to evaluate response to ABT therapy in prostate cancer patients. EGF +61 G>A genotypes were detected by PCR-RFLP. Results: We found increased risk in G carriers, after age-adjusted regression analysis, for being diagnosed with Gleason >= 7 and with metastatic disease compared with control group (CG; age-adjusted odds ratio, 3.37, P = 0.004 and age-adjusted odds ratio, 2.61, P = 0.043, respectively). Kaplan-Meier survival analysis and log-rank test showed an influence of EGF +61 G >A polymorphism in time to relapse during ABT (P = 0.018). Conclusions: EGF functional polymorphism may contribute to earlier relapse in ABT patients, supporting the involvement of EGF as an alternative pathway in hormone-resistant prostatic tumors. Furthermore, our results lend support to EGF-EGF receptor pathway as an additional therapeutic target during hormonal treatment.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5