Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Eur Urol. 2019 Jul;76(1):33-40. doi: 10.1016/j.eururo.2018.09.041. Epub 2018 Oct 6.
Growing evidence shows that clinical and molecular subtypes of prostate cancer (PCa) have specific risk factors. Observational studies suggest that physical activity may lower the risk of aggressive PCa. To our knowledge, the association between physical activity and PCa defined by TMPRSS2:ERG has not been evaluated.
To prospectively examine the association between physical activity and risk of PCa defined by clinical features and TMPRSS2:ERG.
DESIGN, SETTING, AND PARTICIPANTS: We studied 49160 men aged 40-75 yr in the Health Professionals Follow-up Study from 1986 to 2012. Data was collected at baseline and every 2 yr with >90% follow-up. Total and vigorous physical activity were measured in metabolic equivalent of task (MET)-h/wk.
Advanced PCa was defined as stage T3b, T4, N1, or M1 at diagnosis and lethal PCa as distant metastases or death due to disease over follow-up. Presence of TMPRSS2:ERG was estimated by immunohistochemistry of ERG protein expression. Cox proportional hazards models were used to obtain multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of subtype-specific PCa.
During 26 yr of follow-up, 6411 developed PCa overall and 888 developed lethal disease. There were no significant associations between total physical activity and risk of PCa in the overall cohort. In multivariable-adjusted models, men in the highest quintile of vigorous activity had a significant 30% lower risk of advanced PCa (HR: 0.70, 95% CI: 0.53-0.92) and 25% lower risk of lethal PCa (HR: 0.75, 95% CI: 0.59-0.94) than men in the lowest quintile of vigorous activity. The association was independent of screening history. Vigorous activity was not associated with total PCa in the overall cohort but was inversely associated among highly screened men (top vs bottom quintile, HR: 0.83, 95% CI: 0.70-0.97). Of all cases, 945 were assayed for ERG (48% ERG-positive). Men with higher vigorous activity had a lower risk of ERG-positive PCa (top vs bottom quintile, HR: 0.71, 95% CI: 0.52-0.97). There was no significant association with the risk of ERG-negative disease (p heterogeneity=0.09).
Our study confirms that vigorous physical activity is associated with lower risk of advanced and lethal PCa and provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease.
The identification of modifiable lifestyle factors for prevention of clinically important prostate cancer (PCa) is needed. In this report, we compared risk of PCa in men with different levels of physical activity. Men with higher vigorous activity had a lower risk of developing advanced and lethal PCa and PCa with the common TMPRSS2:ERG gene fusion.
越来越多的证据表明，前列腺癌（PCa）的临床和分子亚型具有特定的危险因素。观察性研究表明，体力活动可能降低侵袭性 PCa 的风险。据我们所知，TMPRSS2:ERG 定义的 PCa 与体力活动之间的关联尚未得到评估。
前瞻性研究体力活动与 TMPRSS2:ERG 定义的临床特征和 PCa 风险之间的关系。
设计、地点和参与者：我们研究了 1986 年至 2012 年间健康专业人员随访研究中的 49160 名 40-75 岁的男性。数据在基线和每 2 年收集一次，随访率超过 90%。总体力活动和剧烈体力活动以代谢等效物（MET）-h/wk 衡量。
高级 PCa 定义为诊断时 T3b、T4、N1 或 M1 期，致命性 PCa 定义为远处转移或因疾病导致的死亡。通过 ERG 蛋白表达的免疫组织化学来估计 TMPRSS2:ERG 的存在。使用 Cox 比例风险模型获得特定亚组 PCa 发病率的多变量风险比（HR）和 95%置信区间（CI）。
在 26 年的随访中，6411 人患有总体 PCa，888 人患有致命性疾病。总体力活动与总体队列中 PCa 的风险之间没有显著关联。在多变量调整模型中，剧烈活动最高五分位的男性患晚期 PCa 的风险显著降低 30%（HR：0.70，95%CI：0.53-0.92），致命性 PCa 的风险降低 25%（HR：0.75，95%CI：0.59-0.94）比剧烈活动最低五分位的男性。这种关联独立于筛查史。剧烈活动与总体队列中的总 PCa 无关，但在高度筛查的男性中呈负相关（最高与最低五分位，HR：0.83，95%CI：0.70-0.97）。在所有病例中，有 945 例进行了 ERG 检测（48%为 ERG 阳性）。体力活动较多的男性患 ERG 阳性 PCa 的风险较低（最高五分位与最低五分位，HR：0.71，95%CI：0.52-0.97）。与 ERG 阴性疾病的风险无显著相关性（p 异质性=0.09）。
我们的研究证实，剧烈体力活动与较低的高级和致命性 PCa 风险相关，并为 TMPRSS2:ERG 阳性疾病风险较低提供了新的证据。
需要确定可改变的生活方式因素以预防具有临床意义的前列腺癌（PCa）。在本报告中，我们比较了不同体力活动水平的男性患 PCa 的风险。剧烈活动较多的男性患高级和致命性 PCa 以及常见的 TMPRSS2:ERG 基因融合 PCa 的风险较低。
