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Clin Cancer Res. 2008 Jun 1;14(11):3367-71. doi: 10.1158/1078-0432.CCR-07-5119.

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

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  • 1Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto Centre.

Abstract

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 +61 G>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 > or =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.

[PubMed - indexed for MEDLINE]
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