Cancer and Diabetes

Diabetes and cancer are both common diseases and share several behavioral risk factors, including obesity, smoking, dietary factors, and physical inactivity, and disease pathways, such as hyperglycemia and hyperinsulinemia. According to data from the National Health Interview Surveys 2009–2010, after standardizing for age, 11.5% of U.S. adults with diabetes had a history of any cancer (excluding skin cancer), which was significantly greater than the estimate of 8.9% in adults without diabetes. This chapter discusses knowledge of the relationship between diabetes and various cancer outcomes, with emphases on epidemiologic and clinical evidence. Data from large observational studies and meta-analyses have shown that diabetes is significantly and positively associated with increased overall cancer risk and specific risk of pancreas (pooled relative risk [RR] 1.94, 95% confidence interval [CI] 1.66–2.27), colon (pooled RR 1.38, 95% CI 1.26–1.51), rectum (pooled RR 1.20, 95% CI 1.09–1.31), liver (pooled RR 2.20, 95% CI 1.7–3.0), kidney (pooled RR 1.42, 95% CI 1.06–1.91), bladder (pooled RR 1.29, 95% CI 1.08–1.54), breast (pooled RR 1.27, 95% CI 1.16–1.39), and endometrium (pooled RR 2.10, 95% CI 1.75–2.53) cancers, while negatively associated with the risk of prostate cancer (pooled RR 0.84, 95% CI 0.76–0.93). However, some of the meta-analyses included heterogeneous populations or study designs, resulting in problems of concluding the combining effects. Large cohort studies have found that diabetes increases cancer mortality. The American Cancer Society Cancer Prevention Study II reported that diabetes increased cancer mortality for colon (RR 1.20, 95% CI 0.77–1.27 in men; RR 1.24, 95% CI 1.07–1.43 in women), liver (RR 2.19, 95% CI 1.76–2.75 in men; RR 1.37, 95% CI 0.94–2.00 in women), pancreas (RR 1.48, 95% CI 1.27–1.73 in men; RR 1.44, 95% CI 1.21–1.72 in women), bladder (RR 1.43, 95% CI 1.14–1.80 in men; RR 1.30, 95% CI 0.85–2.00 in women), and breast (RR 1.27, 95% CI 1.11–1.45 in women) cancers. Certain diabetes medications are suggested to be associated with decreased or increased risk of cancer. However, various biases and confounding due to observational design or data analysis pitfalls may lead to biased conclusions. In the other direction, certain cancer treatments, such as chemotherapy for breast cancer, androgen deprivation therapy for prostate cancer, surgical resection of the pancreas, and steroid therapy, could increase the risk of diabetes through weight gain, insulin resistance, insulin intolerance, or hyperglycemia. Meta-analyses indicate diabetes is associated with increased mortality in patients with any cancer (hazard ratio [HR] 1.41, 95% CI 1.28–1.55), as well as cancers of the endometrium (pooled HR 1.76, 95% CI 1.34–2.31), breast (pooled HR 1.49, 95% CI 1.35–1.65), colorectum (pooled HR 1.32, 95% CI 1.24–1.41), prostate (pooled HR 1.57, 95% CI 1.12–2.20), and liver (pooled HR 1.34, 95% CI 1.18–1.51). Furthermore, diabetes is associated with an increased odds of postoperative mortality across all cancer types (pooled odds ratio 1.51, 95% CI 1.13–2.02). The American Diabetes Association and American Cancer Society Consensus Panel has recommended several strategies for primary and secondary preventions. The panel recommended that healthy diet, physical activity, and weight management should be advised for all. In addition, doctors should screen diabetic patients for cancer as recommended for all people in their age and sex groups. Finally, for most diabetic patients, cancer risk should not be a major factor in choosing diabetes treatment.