Diabetes mellitus (DM), one of the metabolic diseases which is characterized by sustained hyperglycemia, is a life-threatening disease. The global prevalence of DM is on the rise, mainly in low- and middle-income countries. Diabetes is a major cause of blindness, heart attacks, kidney failure, stroke, and lower limb amputation. Type 2 diabetes mellitus (T2DM) is a form of diabetes that is characterized by high blood sugar and insulin resistance. T2DM can be prevented or delayed by a healthy diet, regular physical activity, maintaining normal body weight, and avoiding alcohol and tobacco use. Ethanol and its metabolites can cause differentiation defects in stem cells and promote inflammatory injury and carcinogenesis in several tissues. Studies have suggested that diabetes can be treated, and its consequences can be avoided or delayed with proper management. DM has a greater risk for several cancers, such as breast, colorectal, endometrial, pancreatic, gallbladder, renal, and liver cancer. The incidence of cancer is significantly higher in patients with DM than in those without DM. In addition to DM, alcohol abuse is also a risk factor for many cancers.
The possible biological links between diabetes mellitus or impaired glucose tolerance and cancer comprise hyperinsulinemia, hyperglycemia, and fat-induced chronic inflammation. DM is a known risk factor for several cancers [1], resulting from insulin resistance induced by a paraneoplastic syndrome [2] or pancreatic β-cell dysfunction [3]. Mechanistically, hyperglycemia may cause hyperinsulinemia, providing growth signals to positively stimulate the expansion of cancer [4,5,6]. In addition, it has been demonstrated that moderate alcohol intake had no significant impact, whereas high alcohol intake was associated with an increased risk of breast and gastrointestinal cancer [7,8,9,10].
According to the National Diabetes Statistics Report, a periodical publication by the Centers for Disease Control and Prevention (CDC), during 1999–2016, the age-adjusted prevalence of total diabetes significantly increased among adults aged 18 years or older. Prevalence estimates were 9.5% in 1999–2002 and 12.0% in 2013–2016. Among the overall US population, the crude estimates for 2018 were that 34.2 million people of all ages or 10.5% of the US population had diabetes. Furthermore, 34.1 million adults aged 18 years or older, or 13.0% of all US adults, had diabetes. Age-adjusted data for 2017–2018 indicated that non-Hispanic blacks (8.2 per 1000 persons) and people of Hispanic origin (9.7 per 1000 persons) had a higher incidence of diabetes compared to non-Hispanic whites (5.0 per 1000 persons). According to the National Institute of Diabetes and Digestive and Kidney Diseases, diabetes is the seventh leading cause of death in the United States.
In 2017, the International Agency for Research on Cancer (IARC) concluded that obesity is a risk factor of cancer of 13 anatomic sites [11]. The direct association of diabetes mellitus with pancreatic, liver, breast, endometrium, bladder, and kidney cancer has been demonstrated. In addition to obesity and diabetes, other risk factors of cancer are alcohol abuse, genetics (family history), smoking, and exposure to toxic chemicals ( Figure 1 ). Recent studies have shown an association between the incidence of cancer and anti-diabetic medications. Furthermore, the use of metformin (a drug for type 2 diabetes mellitus) is associated with a reduced risk of cancer [12,13,14,15,16] or cancer mortality [17].
Figure 1. Risk factors of cancer. There are several risk factors for cancer. Obesity (IL-1β, TAN, PSC, desmoplasia), diabetes mellitus (IGF-1, p38 MAPK, IL-6, TNF-β, VEGF, and NF-κB), and genetics (mutations in K-ras, BRCA2, and STK11) are biological risk factors for cancer. Toxic chemicals (chlorinated hydrocarbons and polycyclic aromatic hydrocarbons), alcohol abuse (acetaldehyde, ROS, ADH1, and ALDH2), and smoking (nicotine, hydrogen cyanide, formaldehyde, lead, arsenic, ammonia, benzene, carbon monoxide, nitrosamines, and polycyclic aromatic hydrocarbons), are external or environmental risk factors of cancer. Smoking is known as a strong carcinogen in many cancers. Most cancer cases are attributed to environmental factors but a small percentage are involved in gene mutations and hereditary traces. Peutz–Jeghers syndrome (PJS) is caused by mutations in the tumor suppressor STK11 gene.