Department of Surgery, School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
Diabetologia. 2012 Jun;55(6):1619-32. doi: 10.1007/s00125-012-2526-0. Epub 2012 Apr 4.
In this paper we address methodological aspects of aetiological importance in the link between diabetes and mortality in patients with cancer. We identified nine key points on the cancer pathway at which confounding may arise-cancer screening use, stage at diagnosis, cancer treatment selection, cancer treatment complications and failures, peri-treatment mortality, competing risks for long-term mortality, effects of type 2 diabetes on anti-cancer therapies, effects of glucose-lowering treatments on cancer outcome and differences in tumour biology. Two types of mortality studies were identified: (1) inception cohort studies that evaluate the effect of baseline diabetes on cancer-related mortality in general populations, and (2) cohorts of patients with a cancer diagnosis and pre-existing type 2 diabetes. We demonstrate, with multiple examples from the literature, that pre-existing diabetes affects presentation, cancer treatment, and outcome of several common cancer types, often to varying extents. Diabetes is associated with increased all-cause mortality in cancer patients, but the evidence that it influences cancer-specific mortality is inconsistent. In the absence of data that address the potential biases and confounders outlined in the above framework, we caution against the reporting of cancer-related mortality as a main endpoint in analyses determining the impact of diabetes and glucose-lowering medications on risk of cancer.
在本文中，我们探讨了糖尿病与癌症患者死亡率之间因果关系的方法学方面的重要问题。我们确定了癌症发生途径中可能出现混杂因素的九个关键点——癌症筛查的使用、诊断时的分期、癌症治疗的选择、癌症治疗的并发症和失败、治疗前的死亡率、长期死亡率的竞争风险、2 型糖尿病对抗癌治疗的影响、降血糖治疗对癌症结局的影响以及肿瘤生物学的差异。我们确定了两种类型的死亡率研究：（1）起始队列研究，评估基线糖尿病对一般人群癌症相关死亡率的影响，（2）患有癌症诊断和预先存在的 2 型糖尿病的患者队列。我们通过文献中的多个例子表明，预先存在的糖尿病会影响几种常见癌症类型的表现、癌症治疗和结局，而且往往程度不同。糖尿病与癌症患者的全因死亡率增加有关，但它是否影响癌症特异性死亡率的证据并不一致。在缺乏能够解决上述框架中潜在偏倚和混杂因素的数据的情况下，我们告诫不要将癌症相关死亡率作为分析糖尿病和降血糖药物对癌症风险影响的主要终点进行报告。
