Statin drugs and risk of advanced prostate cancer
Statin drugs and risk of advanced prostate cancer
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DOI：
10.1093/jnci/djj499
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发表时间：
2006-12-20
影响因子：
10.3
通讯作者：
Giovannucci, Edward
中科院分区：
文献类型：
--
作者：
Platz, Elizabeth A.;Leitzmann, Michael F.;Giovannucci, Edward
背景他汀类药物是常用的降胆固醇药物，具有促凋亡和抗转移活性，可能影响癌症风险或进展。以前关于他汀类药物使用与癌症之间关系的流行病学研究结果并不一致。我们调查了他汀类药物使用与总前列腺癌和晚期前列腺癌的关系，后者是预防的最重要终点。研究方法：我们分析了一项正在进行的前瞻性队列研究的数据，该研究包括34989名美国男性卫生专业人员，他们在1990年没有患癌症，并随访至2002年。参与者在两年一次的问卷调查中报告了他们使用降胆固醇药物的情况。通过病历审查确认前列腺癌诊断。根据考克斯比例风险回归模型估计多变量调整的相对风险（RR）。统计检验是双侧的。结果如下：在376939人年的随访中，我们确定了2579例前列腺癌病例，其中316例为晚期（区域浸润性、转移性或致命性）。当前使用他汀类药物和过去或从未使用过他汀类药物的晚期前列腺癌的年龄标准化发病率分别为每10万人年38人和89人。与目前未使用他汀类药物相比，目前使用他汀类药物的晚期疾病的多变量校正相对风险为0.51（95%置信区间[CI] = 0.30至0.86），转移性或致死性疾病的多变量校正相对风险为0.39（95% CI = 0.19至0.77）。在调整前列腺特异性抗原筛查史后，相关性仍然存在（晚期疾病：RR = 0.57，95%CI = 0.30 - 1.11;转移性或致死性疾病：RR = 0.35，95%CI = 0.14 - 0.92）。晚期疾病的风险随着他汀类药物使用时间的延长而降低（P趋势= 0.003）;与从未使用相比，使用少于5年的相对风险为0.60（95%CI = 0.35至1.03），使用5年或更长时间的相对风险为0.26（95%CI = 0.08至0.83）。我们发现他汀类药物的使用与总前列腺癌风险之间没有关联（RR = 0.96，95%CI = 0.85至1.09）。结论：在男性健康专业人员队列中，他汀类药物的使用与前列腺癌的总体风险无关，但与晚期（特别是转移性或致死性）前列腺癌的风险降低相关。
Background. Statins are commonly used cholesterol-lowering drugs that have proapoptotic and antimetastatic activities that could affect cancer risk or progression. Results from previous epidemiologic studies of the association between statin use and cancer have been inconsistent. We investigated the association of statin use with total and advanced prostate cancer, the latter being the most important endpoint to prevent. Methods: We analyzed data from an ongoing prospective cohort study of 34 989 US male health professionals who were cancer free in 1990 and were followed to 2002. Participants reported their use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis was confirmed by medical record review. Multivariable-adjusted relative risks (RRs) were estimated from Cox proportional hazards regression models. Statistical tests were two-sided. Results: During 376939 person-years of follow-up, we ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally invasive, metastatic, or fatal). The age-standardized incidence rates of advanced prostate cancer were 38 and 89 per 100 000 person-years in current statin users and in past or never users, respectively. The multivariable-adjusted relative risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use. The associations remained after adjusting for prostate-specific antigen screening history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower with longer statin use (P-trend = .003); compared with never use, the relative risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09). Conclusions: In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.