Ling Suping, Brown Karen, Miksza Joanne K, Howells Lynne, Morrison Amy, Issa Eyad, Yates Thomas, Khunti Kamlesh, Davies Melanie J, Zaccardi Francesco
Leicester Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, U.K.
Leicester Cancer Research Centre, Leicester Royal Infirmary, University of Leicester, Leicester, U.K.
Diabetes Care. 2020 Sep;43(9):2313-2322. doi: 10.2337/dc20-0204.
Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding.
PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality.
Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and <50% for other cancer incidences, and 92% for pancreatic cancer mortality.
Biases other than unmeasured confounding were not analytically assessed.
Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.
2型糖尿病（T2D）与癌症之间的关联是否具有因果关系仍存在争议。本研究的目的是评估T2D与癌症之间观察性关联对未测量混杂因素的稳健性。
于2019年1月10日系统检索了PubMed、Web of Science和Cochrane图书馆，以查找调查T2D与癌症发病率或死亡率之间关联的观察性研究。
提取队列水平的相对风险（RR）。RR在随机效应荟萃分析中进行合并，并在偏倚分析中使用合并估计值。共纳入151个队列（超过3200万人，110万例癌症病例和15万例癌症死亡）。在荟萃分析中，T2D与多种癌症的发病率相关，从前列腺癌（RR 0.83；95%CI 0.79，0.88）到肝癌（2.23；1.99，2.49），并与胰腺癌死亡率相关（1.67；1.30，2.14）。在偏倚分析中，假设与T2D和癌症均相关的未测量混杂因素的RR为1.5，对于肝癌、胰腺癌和子宫内膜癌，真实效应大小大于RR为1.1（即T2D个体风险增加10%）的研究比例接近100%，胆囊癌为86%，肾癌为67%，结肠癌为64%，结直肠癌为62%，其他癌症发病率<50%，胰腺癌死亡率为92%。
未对未测量混杂因素以外的偏倚进行分析评估。
我们的研究结果强烈提示T2D与肝癌、胰腺癌和子宫内膜癌发病率以及胰腺癌死亡率之间存在因果关联。相反，与其他癌症的关联对未测量混杂因素的稳健性较差。
