Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Department of Epidemiology and Public Health, University of Maryland, Baltimore, MD.
Int J Cancer. 2020 Aug 1;147(3):785-792. doi: 10.1002/ijc.32801. Epub 2019 Dec 19.
Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18-10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06-3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91-1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72-1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.
Ⅰ型肌强直性营养不良(DM1)是一种常染色体显性多系统疾病,其特征为肌强直和肌肉无力。2 型糖尿病(T2D)和癌症已被证明是 DM1 表型的一部分。二甲双胍是一种用于 T2D 管理的成熟药物,被认为对普通人群具有预防癌症的作用。在我们的研究中,我们旨在评估 T2D、二甲双胍的使用与 DM1 患者癌症风险之间的关联。我们从英国临床实践研究数据链接(一个大型初级保健记录数据库)中确定了 913 名 DM1 患者的队列和 12318 名 DM1 无对照的年龄、性别和临床匹配队列。我们使用 Cox 回归模型来评估与无 T2D 的患者相比,T2D 患者中使用二甲双胍或未使用二甲双胍的患者的癌症风险。分别对 DM1 患者和对照组进行了分析。DM1 患者中 T2D 的患病率高于对照组(8%比 3%,p<0.0001)。与无 T2D 的患者相比,患有 T2D 的 DM1 患者更有可能患上癌症(危险比 [HR] = 3.60,95%置信区间 [CI] = 1.18-10.97;p = 0.02),但如果他们使用二甲双胍治疗则并非如此(HR = 0.43,95% CI = 0.06-3.35;p = 0.42)。在对照组中,我们在使用或未使用二甲双胍的患者中均未观察到 T2D 与癌症风险之间存在显著关联(HR = 1.28,95% CI = 0.91-1.79;p = 0.16 和 HR = 1.13,95% CI = 0.72-1.79;p = 0.59,分别)。这些结果表明 T2D 与 DM1 患者的癌症风险之间存在关联,并可能为二甲双胍在 DM1 中的可能应用提供新的见解。