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

描述（由申请人提供）：我们的首要目标是确定致死性前列腺癌的可改变危险因素。在美国，前列腺癌仍然是癌症死亡的第二大原因，但已知的人口统计学和遗传风险因素在延缓进展方面的价值有限。在美国人群中的进一步调查是有问题的，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，任何危险因素和PSA检测之间的关联都很容易压倒适度的重要病因学关联。为了消除这种已知的检测偏差，我们提出了一项前瞻性调查，以确定肥胖、烟草和酒精使用与致命性前列腺癌之间的关系，研究数据来自亚洲队列协会（ACC）。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，它汇集了15项前瞻性队列研究的数据，包括超过45万名男性，随访时间约为350万人年。前列腺癌在亚洲的发病率远低于美国，只有这样的联合体才有可能进行前瞻性研究。采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将按年龄（1岁）和队列分别与10例对照进行匹配。多变量条件logistic回归将用于研究BMI、吸烟和饮酒与致死性前列腺癌之间的关系。该项目提供了一个难得的机会，为致命性前列腺癌的可改变因素提供了第一个系统的前瞻性研究，同时最大限度地减少了选择性PSA检测和后续治疗的检测偏差。我们的研究结果可能会成为建议在亚洲预防前列腺癌死亡率的基础，更普遍的是，在没有常规psa检测的人群中。此外，研究结果还可为有进展到晚期和死亡风险的局限性疾病患者提供辅助护理建议。

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.