涉及葡萄糖和能量代谢途径的基因多态性与前列腺癌：与二甲双胍的相互作用。
Polymorphisms of Genes Involved in Glucose and Energy Metabolic Pathways and Prostate Cancer: Interplay with Metformin.
机构信息
School of Medicine, University of Tampere, Tampere, Finland; Department of Urology, Tampere University Hospital, Tampere, Finland.
Institute of Biosciences and Medical Technology / BioMediTech and Fimlab Laboratories, University of Tampere, Tampere, Finland.
出版信息
Eur Urol. 2015 Dec;68(6):1089-97. doi: 10.1016/j.eururo.2015.03.026. Epub 2015 Mar 26.
BACKGROUND
Energy metabolism is important in cancer proliferation and progression, but its role in prostate cancer (PCa) remains unclear.
OBJECTIVE
We explored whether single-nucleotide polymorphisms (SNPs) of genes involved in energy metabolic pathways are associated with PCa risk and prognosis, and whether antidiabetic treatment modifies any such association.
DESIGN, SETTING, AND PARTICIPANTS: The PRACTICAL Consortium genotyped 397 SNPs among 3241 screened participants (including 801 PCa cases) in the Finnish Prostate Cancer Screening Trial and 1983 hospital-based PCa cases. Information on medication use was obtained from a national prescription database.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Genetic risk scores were calculated in terms of SNPs associated with PCa incidence or survival at a significance level of p < 5×10(-3). Hazard ratios for PCa and disease-specific death were calculated via Cox regression modelling. The predictive value of the genetic risk score was evaluated using receiver operating characteristic and Harrell's c-index analyses.
RESULTS AND LIMITATIONS
A total of 30 SNPs were associated with PCa risk and ten SNPs with survival. The genetic risk score was consistently associated with PCa survival. The risk association was non-significantly weaker in metformin users. The genetic risk score did not improve prediction of PCa risk, but slightly improved the ability to predict PCa survival when added to conventional predictors (c-index improved from 87.4 to 87.9; p<0.001). A limitation is that information on diabetes apart from medication use was unavailable for the study population.
CONCLUSIONS
SNPs of genes involved in energy metabolic pathways are associated with PCa survival. This suggests an important role of glucose metabolism in PCa progression, which could point to new avenues for prevention of PCa death.
PATIENT SUMMARY
Genetic changes in glucose and energy metabolic pathways are associated with a higher risk of high-risk prostate cancer and adverse outcomes.
背景
能量代谢在癌症的增殖和进展中很重要，但它在前列腺癌（PCa）中的作用尚不清楚。
目的
我们探讨了参与能量代谢途径的基因的单核苷酸多态性（SNP）是否与 PCa 的风险和预后相关，以及糖尿病治疗是否会改变这种关联。
设计、地点和参与者：PRACTICAL 联盟在芬兰前列腺癌筛查试验中对 3241 名筛查参与者（包括 801 名 PCa 病例）中的 397 个 SNP 进行了基因分型，并对 1983 名基于医院的 PCa 病例进行了基因分型。药物使用信息来自国家处方数据库。
结局测量和统计分析
根据与 PCa 发病率或生存相关的 SNP，以在 5×10(-3) 显著性水平下计算遗传风险评分。通过 Cox 回归模型计算 PCa 和疾病特异性死亡的风险比。通过接收者操作特征和 Harrell 的 c 指数分析评估遗传风险评分的预测价值。
结果和局限性
共有 30 个 SNP 与 PCa 风险相关，10 个 SNP 与生存相关。遗传风险评分与 PCa 生存始终相关。二甲双胍使用者的风险关联不显著减弱。遗传风险评分不能提高 PCa 风险预测，但当添加到常规预测因子时，可略微提高预测 PCa 生存的能力（c 指数从 87.4 提高到 87.9；p<0.001）。一个局限性是研究人群中除了药物使用外，没有关于糖尿病的信息。
结论
参与能量代谢途径的基因的 SNP 与 PCa 生存相关。这表明葡萄糖代谢在 PCa 进展中起着重要作用，这可能为预防 PCa 死亡开辟新途径。
患者总结
葡萄糖和能量代谢途径的遗传变化与高危前列腺癌和不良结局的风险增加相关。
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