A meta-analysis of six case-control studies and nine cohort studies found that diabetes mellitus increased the incidence of colon cancer and rectal cancer by approximately 1.43- and 1.33-fold, respectively [3].

In a meta-analysis, diabetes mellitus was found to increase the incidence of pancreatic cancer by approximately 1.5 times. A study examining the association of baseline fasting blood glucose levels with cancer incidence and cancer-related mortality over a 10-year period using National Health Insurance Service data revealed a significant association between increased blood glucose levels, even within the prediabetic range, and both the incidence of and mortality from pancreatic cancer [4].

Since insulin is produced in the pancreas and transported to the liver via the hepatic portal vein, the liver is naturally exposed to high concentrations of insulin. Furthermore, factors such as diabetes-related fat accumulation, nonalcoholic fatty liver, and liver cirrhosis make individuals more susceptible to HCC. In a US study that analyzed the Surveillance Epidemiology and End-Results Program (SEER)-Medicare database, diabetes mellitus was associated with a twofold to threefold increase in the risk of HCC, even after adjusting for other risk factors such as hepatitis B, hepatitis C, and alcohol consumption [5].

Diabetes mellitus is known to increase the risk of breast cancer and endometrial cancer in women, which is thought to be related to elevated estrogen levels due to a decrease in sex hormone–binding protein [6,7].

Diabetes reduces the incidence of prostate cancer (excluding advanced prostate cancer) in men, and this decrease is believed to be due to a reduction in testosterone levels [8].

In Korea, a study examined the incidence and mortality rates of cancer in individuals with diabetes mellitus over a 10-year period using data from the National Health Insurance Service. After adjusting for smoking and alcohol consumption, higher fasting blood glucose levels were associated with an increased incidence of all cancers. Pancreatic cancer demonstrated the strongest association with fasting blood glucose levels. Fasting blood glucose levels were also linked to esophageal cancer, HCC, and colorectal cancer in men, as well as HCC and cervical cancer in women. Furthermore, a study utilizing National Health Insurance Service data from 2002 to 2013 revealed that the leading causes of death among patients with type 2 diabetes mellitus were malignant neoplasm (24.8%), diabetes mellitus (22.0%), cerebrovascular disease (11.2%), ischemic heart disease (6.2%), and other causes (31.3%). This indicates that cancer is the primary cause of death in patients with diabetes mellitus [9].

Among the common risk factors for diabetes mellitus and cancer, obesity is the most important. Both obesity and cancer are increasingly prevalent worldwide, posing a major threat to human health. Numerous studies have investigated the association between these two diseases, consistently confirming that obesity increases the risk of developing several types of cancer. In 2002, the International Agency for Research on Cancer (IARC) reported that various cancers were associated with obesity, including colon cancer, rectal cancer, postmenopausal breast cancer, endometrial cancer, renal cancer, and esophageal adenocarcinoma [11]. In 2007, the World Cancer Research Fund (WCRF) added pancreatic cancer to the list of cancers with a clear association with obesity and identified gallbladder cancer as likely being associated with obesity [12].

It has been proposed that obesity significantly increases the risk of developing cholelithiasis, gastroesophageal reflux disease, and nonalcoholic fatty liver. In turn, these conditions may result in a higher incidence of gallbladder cancer, esophageal cancer, and HCC, respectively. Insulin, insulin-like growth factors, sex hormones, and adipokines are believed to link obesity and cancer. It has also been suggested that the chronic inflammatory state induced by obesity may lead to cellular immune dysfunction and alterations in blood hormone levels, potentially accelerating cancer progression.

Hyperglycemia may contribute to the development of cancer, as evidenced by the association between elevated blood glucose levels and a higher incidence of cancer, even within the normal range. Furthermore, hyperglycemia can lead to energy dysregulation in cells and weakened immunity within the body. Numerous studies have discovered that hyperglycemia provides an ample supply of glucose for energy-hungry cancer cells, potentially playing a role in resistance to apoptosis and chemotherapy [13].

When insulin resistance leads to consistently high blood insulin concentrations, insulin-like growth factors and insulin receptors are persistently stimulated. This results in protein synthesis and cell proliferation while inhibiting apoptosis. Moreover, elevated insulin indirectly reduces sex hormone–binding globulin levels, leading to increased estrogen concentrations in both men and women, as well as elevated testosterone concentrations in women. In menopausal women, a rise in endogenous sex hormones has been linked to an increased incidence of breast and endometrial cancer [14,15].

Oxidative stress production is highly sensitive to hyperglycemia, leading to the overexpression of intracellular oxidative stress response genes and subsequent DNA damage. Furthermore, numerous inflammatory mediators, such as fatty acids, interleukin-6, plasminogen activator inhibitor-1, adiponectin, leptin, and tumor necrosis factor-α, play a role in the development and progression of cancer [15].

Obesity is associated with breast, colon, rectal, endometrial, pancreatic, esophageal, renal, and gallbladder cancer and HCC. Increased physical activity has been shown to help prevent colon, breast, and endometrial cancer. Studies have also found that smoking can increase the incidence of laryngeal, tracheal, bronchial, lung, upper gastrointestinal, bladder, renal, pancreatic, and cervical cancer, HCC, as well as leukemia. Additionally, excessive alcohol consumption has been associated with a higher incidence of oral, pharyngeal, laryngeal, esophageal, colon, rectal, and breast cancer and HCC. Therefore, to reduce the risk of cancer, it is essential to maintain regular physical activity and an appropriate weight, particularly for patients with diabetes mellitus, while also avoiding smoking and excessive alcohol consumption [16].

Most patients with type 2 diabetes mellitus are middle-aged or older adults, which is when the incidence of cancer increases. As the life expectancy of patients with diabetes mellitus rapidly improves due to advancements in treatments, it is crucial to emphasize regular cancer screening for these individuals. More frequent screenings should be considered for HCC, pancreatic, endometrial, colon, rectal, breast, and bladder cancer, as these have been found to develop more frequently in patients with type 2 diabetes mellitus than their counterparts in the same age group. In particular, regular screening is strongly recommended for HCC, pancreatic, and endometrial cancer, as these have been reported to have a more than twofold higher relative risk in previous meta-analyses [17].