Suping Ling1, Karen Brown2, Joanne K Miksza3, Lynne Howells2, Amy Morrison3, Eyad Issa2,4, Thomas Yates3,5, Kamlesh Khunti3, Melanie J Davies3,5, Francesco Zaccardi3. 1. Leicester Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, U.K. sl617@leicester.ac.uk. 2. Leicester Cancer Research Centre, Leicester Royal Infirmary, University of Leicester, Leicester, U.K. 3. Leicester Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, U.K. 4. Leicester HPB Unit, Leicester General Hospital, Leicester, U.K. 5. National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, U.K.
Abstract
BACKGROUND AND PURPOSE: 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. DATA SOURCES AND STUDY SELECTION: 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. DATA EXTRACTION AND DATA SYNTHESIS: 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. LIMITATIONS: Biases other than unmeasured confounding were not analytically assessed. CONCLUSIONS: 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.
BACKGROUND AND PURPOSE: 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. DATA SOURCES AND STUDY SELECTION: 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. DATA EXTRACTION AND DATA SYNTHESIS: 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 cancermortality. LIMITATIONS: Biases other than unmeasured confounding were not analytically assessed. CONCLUSIONS: Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancermortality. Conversely, associations with other cancers were less robust to unmeasured confounding.
Authors: Kajsa Sjöholm; Lena M S Carlsson; Per-Arne Svensson; Johanna C Andersson-Assarsson; Felipe Kristensson; Peter Jacobson; Markku Peltonen; Magdalena Taube Journal: Diabetes Care Date: 2022-02-01 Impact factor: 19.112
Authors: Amina Amadou; Heinz Freisling; Mazda Jenab; Konstantinos K Tsilidis; Antonia Trichopoulou; Paolo Boffetta; Bethany Van Guelpen; Olatz Mokoroa; Tom Wilsgaard; Frank Kee; Ben Schöttker; José M Ordóñez-Mena; Satu Männistö; Stefan Söderberg; Roel C H Vermeulen; J Ramón Quirós; Linda M Liao; Rashmi Sinha; Kari Kuulasmaa; Hermann Brenner; Isabelle Romieu Journal: Br J Cancer Date: 2021-03-26 Impact factor: 7.640
Authors: Kristy T K Lau; Lui Ng; Jason W H Wong; Herbert H F Loong; Wendy W L Chan; Chi Ho Lee; Carlos K H Wong Journal: Rev Endocr Metab Disord Date: 2021-07-17 Impact factor: 6.514