Teixeira A L, Ribeiro R, Morais A, Lobo F, Fraga A, Pina F, Calais-da-Silva F M, Calais-da-Silva F E, Medeiros R
Molecular Oncology Group-CI and Department of Virology, Portuguese Institute of Oncology, Porto Centre, 4200-072 Porto, Portugal.
Pharmacogenomics J. 2009 Oct;9(5):341-6. doi: 10.1038/tpj.2009.20. Epub 2009 Jun 2.
Proliferative mechanisms involving the epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta(1)) ligands are potential alternative pathways for prostate cancer (PC) progression to androgen independence (AI). Thus, the combined effect of EGF and TGFB1 functional polymorphisms might modulate tumor microenvironment and consequently its development. We studied EGF+61G>A and TGFB1+869T>C functional polymorphisms in 234 patients with PC and 243 healthy individuals. Intermediate- and high-proliferation genetic profile carriers have increased risk for PC (odds ratio (OR)=3.76, P=0.007 and OR=3.98, P=0.004, respectively), when compared with low proliferation individuals. Multivariate analysis showed a significantly lower time to AI in the high proliferation group, compared with the low/intermediate proliferation genetic profile carriers (HR=2.67, P=0.039), after adjustment for age, metastasis and stage. Results suggest that combined analysis of target genetic polymorphisms may contribute to the definition of cancer susceptibility and pharmacogenomic profiles. Combined blockage of key molecules in proliferation signaling pathways could be one of the most promising strategies for androgen-independent prostate cancer.
涉及表皮生长因子（EGF）和转化生长因子β（TGF-β1）配体的增殖机制是前列腺癌（PC）进展为雄激素非依赖性（AI）的潜在替代途径。因此，EGF和TGFB1功能多态性的联合作用可能会调节肿瘤微环境，进而影响其发展。我们研究了234例PC患者和243例健康个体中的EGF+61G>A和TGFB1+869T>C功能多态性。与低增殖个体相比，中高增殖基因谱携带者患PC的风险增加（优势比（OR）分别为3.76，P=0.007和OR=3.98，P=0.004）。多变量分析显示，在调整年龄、转移和分期后，高增殖组进展为AI的时间显著短于低/中增殖基因谱携带者（风险比（HR）=2.67，P=0.039）。结果表明，对目标基因多态性进行联合分析可能有助于确定癌症易感性和药物基因组学特征。联合阻断增殖信号通路中的关键分子可能是雄激素非依赖性前列腺癌最有前景的策略之一。
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