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美国中年男性队列中他汀类药物的使用与结直肠癌风险:一项前瞻性队列研究。

Statin use and risk of colorectal cancer in a cohort of middle-aged men in the US: a prospective cohort study.

作者信息

Flick E Dawn, Habel Laurel A, Chan K Arnold, Haque Reina, Quinn Virginia P, Van Den Eeden Stephen K, Sternfeld Barbara, Orav Endel J, Seeger John D, Quesenberry Charles P, Caan Bette J

机构信息

Division of Research, Kaiser Permanente, Oakland, California 94612, USA.

出版信息

Drugs. 2009 Jul 30;69(11):1445-57. doi: 10.2165/00003495-200969110-00004.

Abstract

BACKGROUND

Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer.

OBJECTIVE

To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization.

METHODS

We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45-69 years who enrolled in the California Men's Health Study in 2002-3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders.

RESULTS

During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of >or=5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers.

CONCLUSION

These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for >or=5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.

摘要

背景

许多可改变的因素与降低结直肠癌风险相关,包括长期使用非甾体抗炎药(NSAIDs)。因此,从生物学角度来看,3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂(他汀类药物)这种同样具有抗炎作用的治疗药物,也可能与降低结直肠癌风险有关。

目的

在一个参加了预付费综合健康维护组织的中年男性大队列中,研究他汀类药物的使用与结直肠癌风险之间的关联。

方法

我们对1991年在南加州、1994年在北加州开始的自动化凯泽永久医疗集团(KP)门诊药房记录中,69115名年龄在45 - 69岁的北加州和南加州KP成员进行了一项前瞻性队列研究。通过与KP加州癌症登记处的数据链接来确定结直肠癌病例。他汀类药物暴露情况根据自动化KP门诊药房记录估算(南加州自1991年、北加州自1994年有记录),并被视为随时间变化的因素。使用Cox比例风险回归分析来估计风险比和95%置信区间(CIs),同时控制潜在的混杂因素。

结果

在最长3.5年的随访期间,共确定了171例结直肠癌病例。与未使用他汀类药物相比,曾经使用他汀类药物的调整后风险比为0.89(95%CI 0.61,1.30)。使用他汀类药物≥5年的风险比为0.83(95%CI 0.43,1.63)。结果在疾病类型或严重程度方面没有明显差异。也没有证据表明规律使用NSAIDs会改变这种效应。然而,分层分析因样本量小而受到限制。

结论

这些发现几乎不支持他汀类药物的使用与男性结直肠癌风险之间存在关联。有一些迹象表明使用他汀类药物≥5年与结直肠癌风险之间存在适度的负相关;然而,不能排除这种观察结果可能与规律使用NSAIDs有关的可能性。

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