Diabetes and cancer: Epidemiological and biological links

Table 1 Non-exhaustive summary of representative association studies between diabetes and various types of cancers in the past 5 years (2015-2019)

Cancer	Ref.	Design	Findings
Pancreatic Cancer	Setiawan et al[15], 2019	Cohort study	Positive association between diabetes and pancreatic cancer
	Chen et al[89], 2017	Cohort study
	Pang et al[14], 2017	Meta-analysis of 22 cohort studies
	Tan et al[90], 2017	Systematic review and meta-analysis
	Dankner et al[91], 2016	Cohort study
	Song et al[92], 2015	Meta-analysis
	Ogunleye et al[93], 2009	Cohort study
	Gupta et al[16], 2006	Cohort study
Liver cancer	Li et al[94], 2017	Case-control study	Increased risk of liver cancer in diabetes
	Wang et al[95], 2017	Meta‐analysis
	Chen et al[96], 2015	Meta-analysis of 21 cohort studies
	El-Serag et al[23], 2006	Systematic review
	Wang et al[22], 2014	Systematic review and meta-analysis	Diabetes is independently associated with a poorer survival in HCC patients
	Lai et al[20], 2006	Cohort study	Diabetes increases risk of HCC in HCV negative individuals
Colorectal cancer	Zhu et al[97], 2017	Meta-analysis	Positive correlation of diabetes with colorectal cancer
	Guraya et al[98], 2015	Meta-analysis of 8 cohort studies
	Larsson et al[28], 2005	Cohort study
	Amshoff et al[25], 2018	Cohort study	Pre-existing T2DM has no influence on disease-specific and all-cause survival among CRC patients
	Jacobs et al[29], 2016	Cohort study	The aMED score is related to lower mortality only in African-American women
	Campbell et al[27], 2010	Cohort study	Modest association between T2DM and CRC among men, but not among women
Breast cancer	Luo et al[35], 2015	Cohort study	Pre-existing diabetes increases the risk of total mortality among women with breast cancer
	Lipscombe et al[34], 2015	Cross-sectional study	Diabetes may predispose to more aggressive breast cancer
	Alokail et al[32], 2009	Cohort study
	Boyle et al[31], 2012	Meta-analysis	Risk of breast cancer is increased by 27% in diabetic women
Endometrial cancer	Saed et al[99], 2019	Systematic review and meta-analysis	Diabetes increases the risk of endometrial cancer in women
	Saltzman et al[39], 2008	Systematic review of case-control study
	Lindemann et al[37], 2015	Cohort study	Diabetes, but not BMI, is associated with an increased risk of all-cause death and death from EC
Bladder cancer	Xu et al[45], 2017	Meta-analysis of 21 cohort studies and case–control studies	Diabetes increases the risk of bladder cancer
	Turati et al[43], 2015	Case–control study
	Zhu et al[42], 2013	Meta-analysis of 36 observational studies
	Prizment et al[44], 2013	Cohort study	Positive association between diabetes and bladder cancer risk among White post-menopausal women
Prostate cancer	Häggström et al[55], 2018	Cohort study	An inverse association between diabetes and prostate cancer
	Lee et al[54], 2016	Meta‐analysis
	Dankner et al[52], 2016	Cohort study
	Khan et al[100], 2016	Cross-sectional, case-only study
	Fall et al[101], 2013	Case-control study

BMI: Body mass index; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; T2DM: Type 2 diabetes mellitus; CRC: Colorectal cancer; EC: Endometrial cancer.

Table 2 Biological links between diabetes and cancer

Characteristic of diabetes	Consequences which promote cancer
High blood sugar level	DNA damage
	ROS production
	Chronic inflammation
	Promote cancer cell proliferation
	Promote cancer cell growth
	Promote cancer cell metastasis
	Provide alternative energy source for cancer cell survival
High blood insulin level (as in T2DM)	Increase level of IGF-1
	Promote cancer cell proliferation
	Promote cancer cell differentiation
	Promote cancer cell survival
	Promote cancer cell migration
	Promote cancer cell growth
	Promote cancer cell metastasis
Inflammation	Promote cancer cell proliferation
	Accelerate cancer cell growth
	Accelerate cancer cell metastasis
	Promote EMT
	Promote cancer cell survival
	Inhibit certain immune responses

ROS: Reactive oxygen species; T2DM: Type 2 diabetes mellitus; IGF-1: Insulin-like growth factor-1; EMT: Epithelial-to-mesenchymal transition.