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


METHODS
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.
Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto Centre.
Ana L
AL
Teixeira
Ricardo
R
Ribeiro
Diana
D
Cardoso
Daniela
D
Pinto
Francisco
F
Lobo
Avelino
A
Fraga
Francisco
F
Pina
Fernando
F
Calais-da-Silva
Rui
R
Medeiros
D000726:Androgen Antagonists / Q000627:therapeutic use; D016022:Case-Control Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
D000726:Androgen Antagonists; D004815:Epidermal Growth Factor