Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences (FMHS), University of Auckland, Private Bag 92019, Auckland, New Zealand.
Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Sci Rep. 2022 Jan 7;12(1):55. doi: 10.1038/s41598-021-04116-8.
It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo-keto reductase 1C3 (AKR1C3) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.
目前，人们对于基于前列腺特异性抗原（PSA）的筛查是否能有效降低前列腺癌死亡率仍存在争议。这种不确定性可能与筛查中使用的基于年龄的 PSA 截断阈值的缺陷有关。本研究共纳入了 2779 名前列腺癌患者和 1606 名无癌症诊断的男性，他们分别来自新西兰、美国和中国台湾的多项研究。采用多元线性回归和单变量模型分析了 PSA 与人口统计学、生活方式、临床特征（病例组）以及醛酮还原酶 1C3（AKR1C3）rs12529 基因多态性之间的相关性。对病例组进行的多变量合并分析显示，PSA 与人口统计学、生活方式和临床数据显著相关，种族和年龄之间的相互作用进一步改变了这种相关性。对对照组数据的多变量合并分析也表明，人口统计学和生活方式与 PSA 水平显著相关。独立的病例和对照组分析表明，与 PSA 相关的因素在每个队列中都是特定的。单变量分析显示，除了美国-欧洲病例外，所有病例和对照组的年龄和 PSA 之间均存在显著相关性，而病例中的基因分层显示相关性存在差异。数据表明，针对人口统计学、生活方式和遗传学的特定 PSA 截断阈值可能更适合前列腺癌筛查。
