STATIN暴露与降低的癌症风险相关

StephenW

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED RISK OF CANCER
Author(s):

Roger Bedimo1, Fatma Shebl2, Keith M. Sigel3, Sheldon T. Brown4, Kristina Crothers5, Matthew B. Goetz6, Amy C. Justice7, Janet Tate7

1VA North Texas Health Care Center, Dallas, TX, USA,2Yale University, New Haven, CT, USA,3Icahn School of Medicine at Mt Sinai, New York, NY, USA,4James J. Peters VA Medical Center, Bronx, NY, USA,5University of Washington, Seattle, WA, USA,6VA Greater Los Angeles Health Care System, Los Angeles, CA, USA,7VA Connecticut Healthcare System, West Haven, CT, USA
Abstract Body:

Beyond inhibition of cholesterol biosynthesis, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis, and inflammation. Statins may also reduce cancer risk, particularly among HIV-infected (HIV+) subjects who experience chronic inflammation and immune activation. Small observational studies have suggested an association between statin use and lower cancer risk in HIV+ but small sample sizes limited cancer type-specific analyses. Comparison of the association of statin exposure with cancer in HIV+ and HIV-uninfected comparators (HIV-) is also lacking. We used the Veterans Aging Cohort Study (VACS), a large observational cohort with cancer registry linkage and detailed pharmacy data to address these questions

We followed statin users identified between 2000-2012, beginning 180 days after an index date defined as first statin prescription for users and a random visit date in the same year for non-users. To account for known and potential confounders we fit a propensity score (PS) model for statin use including age, calendar year, smoking, chronic diseases (e.g., diabetes, hypertension, HCV co-infection, alcohol use disorder), and laboratory values (e.g., LDL, albumin). We matched each statin user to up to four non-users by PS. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, individual cancers, infection-related cancers (anal, colorectal, head and neck, liver, lymphoma, and stomach) and notinfection-related cancers.

The PS-matched sample included 48,214 participants, of whom 23,512 (48.8%) were incident statin users. Incident cancers were diagnosed in 940 (9.7%) of 9,649 HIV+ and 3,079 (8.0%) in 38,565 uninfected. Overall, statin use was associated with ~20% reduced risk of any cancer [HR 0.82 (95% CI 0.77 – 0.88)] and ~40% lower risk for infection-related cancers [HR 0.62 (95% CI 0.55 – 0.70)]. In general, the association was stronger in HIV+, but the interaction did not reach statistical significance except for non-Hodgkin lymphoma

Statin exposure is associated with lower risk of cancer independent of HIV status. This protective effect appears to be stronger for infection-related cancers.

StephenW

STATIN暴露与降低的癌症风险相关
作者（S）：

Roger Bedimo1，Fatma Shebl2，Keith M. Sigel3，Sheldon T. Brown4，Kristina Crothers5，Matthew B. Goetz6，Amy C. Justice7，Janet Tate7

1VA北德克萨斯州健康护理中心，美国德克萨斯州达拉斯，2Yale大学，美国康涅狄格州纽黑文，3美国纽约州西奈山伊坎医学院，4纽约布朗克斯詹姆斯彼得斯VA医学中心，美国华盛顿大学，美国华盛顿州西雅图6VA大洛杉矶医疗保健系统，美国加利福尼亚州洛杉矶，美国康涅狄格州西黑文7VA康涅狄格医疗系统
抽象身体：

除抑制胆固醇生物合成外，他汀类药物似乎具有多效性，包括调节细胞生长，凋亡和炎症。他汀类药物还可以降低癌症风险，尤其是在经历慢性炎症和免疫激活的HIV感染者（HIV +）受试者中。小型观察研究表明他汀类药物使用与艾滋病毒携带者患癌症风险较低有关，但小样本量限制了癌症类型特异性分析。艾滋病毒+和未感染艾滋病毒的比较者（HIV-）中他汀类药物暴露与癌症之间的关联的比较也缺乏。我们使用了退伍军人衰老队列研究（VACS），这是一个具有癌症登记联动和详细药房数据的大型观察队列来解决这些问题

我们追踪了在2000 - 2012年间确定的他汀类药物使用者，这些药物使用者在索引日期后180天开始，该索引日期被定义为用户的第一次他汀类药物处方，同年非用户的随机访问日期。为了说明已知和潜在的混杂因素，我们使用他汀类药物使用的倾向评分（PS）模型，包括年龄，日历年，吸烟，慢性病（例如糖尿病，高血压，HCV合并感染，酒精使用障碍）和实验室值例如LDL，白蛋白）。我们通过PS将每个他汀类药物使用者与多达四名非使用者相匹配。我们使用Cox比例风险回归模型来估计所有癌症，个体癌症，感染相关癌症（肛门，结肠直肠，头部和颈部，肝脏，淋巴瘤等）与他汀类药物使用相关的危险比（HR）和95％置信区间（CI）和胃）和非感染相关的癌症。

PS匹配样本包括48,214名参与者，其中23,512名（48.8％）是他汀类药物使用者。 9409例HIV感染者中有940例（9.7％）和38565例未感染者中有3,079例（8.0％）确诊为癌症。总体而言，他汀类药物使用与任何癌症发生风险降低约20％相关[HR 0.82（95％CI 0.77 - 0.88）]，感染相关癌症风险降低约40％[HR 0.62（95％CI 0.55 - 0.70）] 。一般来说，艾滋病病毒感染者的关联性更强，但除了非霍奇金淋巴瘤之外，这种相互作用没有达到统计学意义

他汀类药物暴露与独立于HIV状态的癌症风险较低有关。这种保护作用似乎对感染相关癌症更强。