Ananthakrishnan Ashwin N, Cagan Andrew, Cai Tianxi, Gainer Vivian S, Shaw Stanley Y, Churchill Susanne, Karlson Elizabeth W, Murphy Shawn N, Liao Katherine P, Kohane Isaac
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Research Information Services and Computing, Partners HealthCare, Charlestown, Massachusetts.
Clin Gastroenterol Hepatol. 2016 Jul;14(7):973-9. doi: 10.1016/j.cgh.2016.02.017. Epub 2016 Feb 22.
BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are associated with an increased risk of colorectal cancer (CRC). Chemopreventive strategies have produced weak or inconsistent results. Statins have been associated inversely with sporadic CRC. We examined their role as chemopreventive agents in patients with IBD.
We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010. Diagnoses of CRC were determined using validated International Classification of Diseases, 9th revision, Clinical Modification codes. Statin use before diagnosis was assessed through analysis of electronic prescriptions. We performed multivariate logistic regression analyses, adjusting for potential confounders including primary sclerosing cholangitis, smoking, increased levels of inflammation markers, and CRC screening practices to identify an independent association between statin use and CRC. We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use.
In our cohort, 1376 of the patients (12.5%) received 1 or more prescriptions for a statin. Patients using statins were more likely to be older, male, white, smokers, and have greater comorbidity than nonusers. Over a follow-up period of 9 years, 2% of statin users developed CRC compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24-0.53). On multivariate analysis, statin use remained independently and inversely associated with CRC (odds ratio, 0.42; 95% confidence interval, 0.28-0.62). Our findings were robust on a variety of sensitivity and subgroup analyses.
Statin use was associated inversely with the risk of CRC in a large IBD cohort. Prospective studies on the role of statins as chemopreventive agents are warranted.
诸如克罗恩病和溃疡性结肠炎等炎症性肠病（IBD）与结直肠癌（CRC）风险增加相关。化学预防策略产生的结果微弱或不一致。他汀类药物与散发性CRC呈负相关。我们研究了它们在IBD患者中作为化学预防剂的作用。
我们收集了1998年至2010年在大波士顿都会区医院接受治疗的11001例IBD患者的数据。使用经过验证的《国际疾病分类》第九版临床修订版编码确定CRC的诊断。通过分析电子处方评估诊断前他汀类药物的使用情况。我们进行了多变量逻辑回归分析，对包括原发性硬化性胆管炎、吸烟、炎症标志物水平升高和CRC筛查实践等潜在混杂因素进行了调整，以确定他汀类药物使用与CRC之间的独立关联。我们使用倾向评分调整和他汀类药物使用定义的变化进行了敏感性分析。
在我们的队列中，1376例患者（12.5%）接受了1种或更多种他汀类药物的处方。使用他汀类药物的患者比未使用者更可能年龄较大、为男性、白人、吸烟者且合并症更多。在9年的随访期内，2%的他汀类药物使用者发生了CRC，而未使用者为3%（年龄调整后的优势比为0.35；95%置信区间为0.24 - 0.53）。在多变量分析中，他汀类药物的使用仍然与CRC独立且呈负相关（优势比为0.42；95%置信区间为0.28 - 0.62）。我们的发现在各种敏感性和亚组分析中都很稳健。
在一个大型IBD队列中，他汀类药物的使用与CRC风险呈负相关。有必要对他汀类药物作为化学预防剂的作用进行前瞻性研究。
