Affiliations of authors: Division of Hematology/Medical Oncology (LM, CCE, DS, RB) and Division of Molecular and Cellular Biology (DS), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (CCE, SYC, MK); Ontario Institute for Cancer Research, Toronto, Ontario, Canada (CCE).
J Natl Cancer Inst. 2016 Oct 20;109(3). doi: 10.1093/jnci/djw226. Print 2017 Mar.
Metabolic syndrome (MetS) is a risk factor for development of cancer. Because aberrant lipid metabolism is a pathogenic feature of chronic lymphocytic leukemia (CLL), our objective was to determine if CLL patients have a higher prevalence of MetS preceding diagnosis and to determine the impact of lipid-lowering medications on survival.
We conducted a population-based case-control study in Ontario, Canada, using administrative databases of adults age 66 years and older to compare the prevalence of MetS preceding CLL with age- and sex-matched control subjects. Logistic regression was used to study the association between MetS and its components to CLL. The Kaplan-Meier method and Cox Regression were used to investigate survival. All statistical tests were two-sided.
We identified 2124 persons with CLL and 7935 control subjects from January 1, 2000, to December 31, 2005, with follow-up until March 31, 2014, three years from the date of last contact with the health care system, or death. The mean age was 75.6 years, 20.2% had diabetes, 35.8% had hypertension, and 17.6% had dyslipidemia. In multivariable analysis, dyslipidemia (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.44, P < .001) and hypertension (OR = 1.12, 95% CI = 1.01 to 1.25, P = .03) were associated with the development of CLL, whereas MetS and diabetes were not. Lipid-lowering medication was associated with a statistically significant improved survival in patients with CLL (HR = 0.53, 95% CI = 0.47 to 0.61, P < .001).
We demonstrate a higher prevalence of dyslipidemia preceding a diagnosis of CLL compared with control subjects, supporting preclinical data. Lipid-lowering medications appear to confer a survival advantage in CLL. Prospective studies are needed to confirm these results and test their potential as therapeutic applications.
代谢综合征(MetS)是癌症发展的一个风险因素。由于异常的脂质代谢是慢性淋巴细胞白血病(CLL)的一个发病特征,我们的目的是确定 CLL 患者在诊断前是否有更高的 MetS 患病率,并确定降脂药物对生存的影响。
我们在加拿大安大略省进行了一项基于人群的病例对照研究,使用 66 岁及以上成年人的行政数据库,比较 CLL 患者在诊断前的 MetS 患病率与年龄和性别匹配的对照人群。采用 logistic 回归研究 MetS 及其各组成部分与 CLL 的关系。采用 Kaplan-Meier 法和 Cox 回归法研究生存。所有统计检验均为双侧。
我们从 2000 年 1 月 1 日至 2005 年 12 月 31 日确定了 2124 名 CLL 患者和 7935 名对照者,随访至 2014 年 3 月 31 日,即最后一次与医疗保健系统接触或死亡之日起三年。平均年龄为 75.6 岁,20.2%有糖尿病,35.8%有高血压,17.6%有血脂异常。多变量分析显示,血脂异常(比值比[OR] = 1.26,95%置信区间[CI] = 1.11 至 1.44,P <.001)和高血压(OR = 1.12,95%CI = 1.01 至 1.25,P =.03)与 CLL 的发生相关,而 MetS 和糖尿病则没有。降脂药物与 CLL 患者的生存有显著统计学改善相关(HR = 0.53,95%CI = 0.47 至 0.61,P <.001)。
与对照者相比,我们在 CLL 诊断前观察到血脂异常的患病率更高,这支持了临床前数据。降脂药物似乎在 CLL 中提供了生存优势。需要前瞻性研究来证实这些结果,并测试它们作为治疗应用的潜力。