Diabetes-associated cancers

Diabetes is associated with range of cancer types. As discussed elsewhere,many of these cancers over-express the insulin receptor on their surface, and concurrent risk factors for cancer, most notably obesity, may also be present. The associations between diabetes and cancer are particularly strong for pancreatic cancer (although there may be an element of reverse causation), endometrial and hepatocellular carcinoma. Diabetes is also associated with breast, colorectal and bladder cancer. In contrast, there is a negative association with prostate cancer, and the relationship with lung cancer remains undetermined. This entry summarizes a number of studies outlining the association between diabetes and cancer, with brief notes on each type. The specific cancers are considered in more detail in the daughter pages.

Background

There is substantial epidemiologic evidence in various populations indicating that patients with diabetes have an increased risk of several types of cancer (Table 1) [1][2][3][4][5][6][7][8][9][10].

Table 1. Associations between diabetes (mainly type 2) and incidence cancer risk

Authors Cancer type No. cohorts/no. case-control studies No. of cases Risk estimates (95% CIs)
Larsson et al. 2007 [3] Breast (all) 15/5 30,407 1.20 (1.12, 1.28)
Pre-menopausal Not stated Not stated 0.91 (0.62, 1.34)
Post-menopausal Not stated Not stated 1.16 (1.09, 1.24)
Larsson et al. 2005 [4] Colorectal 9/6 26,306 1.30 (1.20, 1.40)
Friberg et al. 2007 [5] Endometrial 3/13 7,596 2.10 (1.93, 3.24)
Larsson & Wolk 2011 [6] Kidney 9/0 8,757* 1.42 (1.06, 1.91)
Larsson et al. 2006 [7] Bladder 3/7 not stated 1.24 (1.08, 1.42)
Huxley et al. 2005 [8] Pancreas 19/17 9,220 1.82| (1.71, 1.94)
El-Serag et al. 2006 [9] Hepatocellular 13/13 not stated 2.50 (1.93, 3.24)
Kasper et al. 2006 [10] Prostate 12/7 20,373 0.84 (0.76, 0.93)

It cannot be over-emphasised that both diabetes and cancer are heterogeneous, and that the relationship between the two must be evaluated for each and every type of cancer. The literature indicates a strong and consistent increase in the risk of cancer in people with type 2 diabetes, but the strength of association depends on the specific cancer site. The risk of cancer in people with diabetes thus requires consideration in terms of specific cancer sites, rather than overall cancer incidence[1] .

Breast

In the Nurses’ Health Study, women with self-reported diabetes had a small but significantly elevated (17%) risk of breast cancer compared to women without diabetes [11]. This finding was independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. The data from the Nurses’ Health Study provide the largest population with the longest follow-up in assessing the association between diabetes and breast cancer. Similarly, a meta-analysis of 5 case-control studies and 15 cohort studies confirmed that diabetes was associated with an increased risk of breast cancer (summary RR: 1.20; 95% CI: 1.12-1.28)[3] . In both the Nurses’ Health Study and the meta-analysis, the increased risk of breast cancer was restricted to post-menopausal women with diabetes [3][11].

Colorectal

A meta-analysis of diabetes and the risk of colorectal cancer included 15 studies (6 case-control and 9 cohort studies), with nearly 2,600,000 participants[4]. The authors found that diabetes was associated with an increased risk of colorectal cancer, compared to individuals without diabetes (summary RR: 1.30; 95% CI: 1.20-1.40) [4]. Importantly, a positive association between diabetes and risk of colorectal cancer remained when only including studies that controlled for two potentially important confounders, physical activity and BMI [4].

Endometrial

A fairly recent meta-analysis looked at the association between diabetes and risk of endometrial cancer [5]. The analysis included 16 case-control and 3 cohort studies, with over 96,000 participants and nearly 7,600 cases of endometrial cancer. The results support a strong relationship between diabetes and risk of endometrial cancer (summary RR: 2.10; 95% CI: 1.75-2.53) [5].

Pancreatic

The positive association between diabetes and pancreatic cancer has been consistently observed in numerous studies. In some of the available literature, it is not clear if the population under study is restricted to type 1 or type 2 diabetes. Huxley et al performed a meta-analysis looking specifically at type 2 diabetes and pancreatic cancer [8]. The authors included 36 studies (17 case-control and 19 cohort studies) from 1966 to 2005, with information on over 9,000 people with pancreatic cancer. Their results support a strong association between type 2 diabetes and pancreatic cancer (summary OR: 1.82; 95% CI: 1.66-1.89). An important consideration in interpreting this elevated risk is the potential for reverse causality, where subclinical cancer developing within the pancreas may lead to symptoms of diabetes [1].

Bladder

A meta-analysis evaluating the association between diabetes and the risk of bladder cancer included 16 studies (7 case-control studies, 3 cohort studies, and 6 cohort studies of patients hospitalized with type 2 diabetes). Diabetes was associated with a modestly increased risk of bladder cancer, compared with no diabetes (summary RR: 1.24; 95% CI: 1.08-1.42)[7] .

Prostate

In contrast to other types of cancer, there appears to be an inverse relationship between diabetes and prostate cancer. This inverse association may be explained by the cancer-promoting role of endogenous testosterone, which is lower in men with type 2 diabetes [12]. Kasper et al conducted a meta-analysis of 19 studies, published between 1971 and 2005, and observed a statistically significant decreased risk of prostate cancer in people with diabetes (summary RR:0.84; 95% CI: 0.76-0.93)[10] .

Liver

A systematic review and meta-analysis of 26 studies (13 case-control and 13 cohort) examined the association between diabetes and liver cancer [13]. Diabetes was associated with a significantly increased risk of liver cancer among case control studies (pooled OR:2.5; 95%CI:1.8-3.5) and cohort studies (pooled RR: 2.5; 95%CI: 1.9-3.2). Importantly, these findings were independent of alcohol use, viral hepatitis, and were consistent in different populations [13]. As the liver is a metabolically active organ, the possibility of reverse causality is also a consideration in interpreting these estimates of increased risk [1].

Lung

There is very limited evidence of the association between diabetes and lung cancer ; in general , there has been no consistent association shown between diabetes and lung cancer. For example, a cohort study using the General Practice Research Database (GPRD) from the United Kingdom, found no increased risk of lung cancer among people with diabetes, compared to nondiabetic controls (HR:0.88; 95%CI: 0.79-0.97)[14].

References

  1. ^ Johnson JA, et al. Diabetes and Cancer (1): Evaluating the temporal relationship between type 2 diabetes and cancer incidence. Diabetologia 2012;55(6):1607-1618.

  2. ^ Nicolucci A. Epidemiological aspects of neoplasms in diabetes. Acta Diabetol 2010;47:87–95.

  3. ^ Larsson SC et al. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007;121:856–862.

  4. ^ Larsson SC et al. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005;97:1679–1686.

  5. ^ Friberg E et al. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007;50:1365–1374.

  6. ^ Larsson SC et al. Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies. Diabetologia 2011;54:1013–1018.

  7. ^ Larsson SC et al. Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia 2006;49:2819–2823.

  8. ^ Huxley R et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005;92:2076–2083.

  9. ^ El-Serag HB et al. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006;4:369–380.

  10. ^ Kasper JS et al. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:2056–2062.

  11. ^ Michels KB et al. Type 2 diabetes and subsequent incidence of breast cancer in the Nurses’ Health Study. Diabetes Care 2003;26:1752-8.

  12. ^ Thompson MM et al. Heart disease risk factors, diabetes, and prostatic cancer in an adult community. Am J Epidemiol 1989;129:511-7.

  13. ^ El-Serag HB et al.The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006;4:369–380.

  14. ^ Hall GC et al. Diabetes and the risk of lung cancer. Diabetes Care 2005;28:590–594.

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