Department of Medical Oncology, Mater Misericordiae University Hospital and St James's Hospital, Dublin, Ireland.
BJU Int. 2012 Dec;110(11 Pt C):E809-18. doi: 10.1111/j.1464-410X.2012.11450.x. Epub 2012 Sep 14.
What's known on the subject? and What does the study add? Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic strategies. Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical behaviour. Genome wide association studies (GWAS) have identified more common genetic variations that explain an estimated 20% of familial prostate cancer risk. In this review, we focus on the potential of germline genetic variation to provide biomarkers for prostate cancer screening, prevention and management. We discuss how germline genetics may have a role in treatment selection if reliable pharmacogenetic predictors of efficacy and toxicity can be identified. We have outlined possible mechanisms for including germline investigation in future prostate cancer clinical trials.
• Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic strategies. • In this review we focus on the potential of germline genetic variation to provide these biomarkers.
• We review the published literature on germline genetics in prostate cancer and examine the possibility of including germline genetic biomarkers in future prostate cancer clinical trials.
• Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical behaviour. • Genome-wide association studies (GWAS) have identified more common genetic variations that explain an estimated 20% of familial prostate cancer risk. • Germline genetics may have a role in treatment selection, if reliable pharmacogenetic predictors of efficacy and toxicity can be identified.
• This rapidly emerging area of prostate cancer research may provide answers to current clinical conundrums in the prostate cancer treatment paradigm. We have outlined possible mechanisms for including germline investigation in future prostate cancer clinical trial design.
前列腺癌是一种异质性疾病，需要生物标志物来预测其发病率和后续的临床行为，以调整筛查、预防和治疗策略。BRCA1、BRCA2 和 HOXB13 等基因中的罕见突变会影响前列腺癌的发病率和/或临床行为。全基因组关联研究（GWAS）已经确定了更多常见的遗传变异，这些变异可以解释约 20%的家族性前列腺癌风险。在这篇综述中，我们专注于种系遗传变异在前列腺癌筛查、预防和管理中的潜在生物标志物。我们讨论了如果能够确定可靠的药物遗传学预测疗效和毒性的预测因子，种系遗传学在治疗选择中可能发挥的作用。我们概述了在未来的前列腺癌临床试验中纳入种系研究的可能机制。
• 前列腺癌是一种异质性疾病，需要生物标志物来预测其发病率和后续的临床行为，以调整筛查、预防和治疗策略。• 在这篇综述中，我们专注于种系遗传变异在提供这些生物标志物方面的潜力。
• 我们回顾了前列腺癌种系遗传学的已发表文献，并研究了在未来的前列腺癌临床试验中纳入种系遗传生物标志物的可能性。
• BRCA1、BRCA2 和 HOXB13 等基因中的罕见突变会影响前列腺癌的发病率和/或临床行为。• 全基因组关联研究（GWAS）已经确定了更多常见的遗传变异，这些变异可以解释约 20%的家族性前列腺癌风险。• 如果能够确定可靠的药物遗传学预测疗效和毒性的预测因子，种系遗传学在治疗选择中可能发挥作用。
• 这一快速发展的前列腺癌研究领域可能为当前前列腺癌治疗模式中的临床难题提供答案。我们已经概述了在未来的前列腺癌临床试验设计中纳入种系研究的可能机制。
