Modifiable Risk Factors for Fatal Prostate Cancer: A Prospective Study In Asia

描述(由申请者提供)：我们的首要目标是确定致命前列腺癌的可改变的危险因素。前列腺癌仍然是美国癌症死亡的第二大原因，但已知的人口统计和遗传风险因素在延缓进展方面的价值有限。在美国人群中进行进一步的研究是有问题的，因为广泛和选择性的前列腺特异性抗原(PSA)检测与诊断阶段密切相关，以至于风险因素和PSA检测之间的任何关联都很容易被重要的病因学关联压倒。为了消除这种已知的检测偏差，我们建议进行一项前瞻性调查，利用亚洲队列联合会(ACC)的数据来确定肥胖、吸烟和饮酒与致命性前列腺癌之间的关联。亚洲国家很少进行PSA检测，亚洲大多数前列腺癌患者被诊断为晚期或转移性疾病。ACC是一个独特的资源，它协调了15项前瞻性队列研究的数据，包括超过45万名男性和大约350万人年的随访。前列腺癌在亚洲的发病率远低于美国，只有这样的财团才有可能进行前瞻性研究。使用嵌套病例对照设计，迄今为止记录的507例前列腺癌死亡病例中的每一例将按年龄(1岁)和队列分别与10名对照匹配。将使用多变量条件Logistic回归来调查BMI、吸烟和饮酒与致命性前列腺癌之间的关系。该项目提供了一个难得的机会，为致命前列腺癌的可修改因素提供第一个系统的前瞻性研究，同时将选择性PSA测试和后续治疗的检测偏差降至最低。我们的结果可能形成在亚洲预防前列腺癌死亡率的建议的基础，更广泛地说，在没有定期进行PSA检测的人群中。此外，这些结果也可能成为对被诊断为有进展到晚期和死亡风险的局部疾病患者的辅助护理建议的基础。 公共卫生相关性：前列腺癌是癌症相关死亡的主要原因，而广泛的筛查导致了对早期和非致命疾病的过度治疗。这项关于致命前列腺癌的可改变因素的前瞻性研究，同时尽可能减少选择性前列腺癌筛查和检测的任何影响。我们的结果可能会建议新的预防或辅助护理策略，以降低死亡率，避免不必要的治疗导致的大小便失禁和阳萎等并发症。

DESCRIPTION (provided by applicant): Our overarching goal is to identify modifiable risk factors for fatal prostate cancer. Prostate cancer remains the second leading cause of cancer-death in the United States (U.S.), but known demographic and genetic risk factors have limited value in delaying progression. Further investigation in U.S. populations is problematic because widespread and selective prostate-specific antigen (PSA) testing is so strongly associated with the stage at diagnosis that any association between a risk factor and PSA testing could easily overwhelm a modest by important etiologic association. To remove this known detection bias, we propose a prospective investigation to determine the association between obesity, tobacco, and alcohol use with fatal prostate cancer using data from the Asian Cohort Consortium (ACC). Asian nations rarely perform PSA tests, and most prostate cancer patients in Asia are diagnosed with advanced or metastatic disease. The ACC is a unique resource that has harmonized data across 15 prospective cohort studies and includes over 450,000 men with approximately 3.5 million person-years follow-up. Prostate cancer is far less common in Asia than the U.S., and a prospective study would only be possible with such a consortium. Using a nested case- control design, each of the 507 recorded prostate cancer deaths to date will be individually matched to 10 controls by age (1 year) and cohort. Multivariable conditional logistic regression will be used to investigate associations between BMI, tobacco, and alcohol use with fatal prostate cancer. This project provides an exceptional opportunity to provide the first systematic prospective investigation of modifiable factors for fatal prostate cancer, while minimizing detection bias from selective PSA testing and subsequent treatment. Our results may form the basis for recommendations to prevent prostate cancer mortality in Asia, and more generally, in populations that are not routinely PSA-tested. Furthermore, results may also form the basis for adjuvant care recommendations among men diagnosed with localized disease by at risk for progression to an advanced stage and for death. PUBLIC HEALTH RELEVANCE: Prostate cancer is a leading cause of cancer-related mortality, while widespread screening had led to the over-treatment of early stage and non-fatal disease. This prospective investigation of modifiable factors for fatal prostate cancers while reducing as much as possible any influence of selective prostate cancer screening and detection. Our results may suggest new prevention or adjuvant care strategies to reduce mortality and avoid comorbidities such as incontinence and impotency derived from unnecessary treatment.