Shared risk factors for cancer
There are major shared modifiable and non-modifiable risk factors in the association between type 2 diabetes and cancer, and hyperglycaemia itself - the hallmark of diabetes - typically appears to play a minor role if any. Non-modifiable risk factors include age, sex and race/ethnicity. Almost 90% of cancers and the majority of diabetes cases are diagnosed after the age of 50, and the risk of diagnosis of either disease increases with age. Males have a higher age-adjusted incidence of diabetes than females, and a similar trend is observed for many cancers. The risk of diabetes and of several cancer types is higher among certain ethnic groups, including African-Americans and First Nations, although socioeconomic differences and other biologic/genetic factors may influence this association. Modifiable risk factors include obesity, sedentary lifestyle, socioeconomic status, smoking, alcohol and medication. Obesity, in particular, is strongly implicated in the specific cancers most commonly associated with type 2 diabetes. Environmental and/or behavioural risk factors play a dominant role in determining risk of type 2 diabetes and cancer, and these risks are potentially modifiable.
The association between diabetes and cancer is potentially confounded by a range of risk factors common to both conditions, and hyperglycaemia itself - the hallmark of diabetes - may be of little importance in determining the association.
Associated risk factors may be non-modifiable (age, gender, ethnicity), or modifiable (obesity, smoking, alcohol, inactivity). The relative importance of any given risk factor will vary with cancer type.
Non-modifiable risk factors
Gender: Males have a higher age-adjusted incidence of diabetes than females, and a similar trend is observed for many cancers.
Ethnicity: In North American studies, the risk of diabetes and of several cancer types is higher among certain ethnic groups, including African-Americans and First Nations, although socioeconomic differences and other biologic/genetic factors may influence this association.
Modifiable risk factors
Type 2 diabetes and cancer share several modifiable risk factors that increase the chance of developing either disease, notably: smoking, sedentary lifestyle, alcohol consumption and overweight/obesity:
Overweight and obesity have been linked with an increased incidence of many cancers, in both men and women. The cancers most consistently associated with overweight and obesity are breast (in postmenopausal women), colon/rectum, endometrium, pancreas, oesophageal adenocarcinoma, kidney, gallbladder, and liver cancers. Obesity is clearly a risk factor for type 2 diabetes, most likely by inducing insulin resistance, which may partly explain this association with cancer. Indeed, there is evidence to suggest that visceral adiposity, a marker of insulin resistance, is associated with risk of both type 2 diabetes, and certain cancers (e.g. colon) independent of BMI. Generalised obesity may also promote cancer through mechanisms independent of insulin resistance. For instance, there is excess oestrogen production in the peripheral adipose tissue of obese individuals, which may increase the risk of oestrogen-dependent tumours such as those of the breast and endometrium.
Diet and Inactivity are potentially important confounding factors to be considered, as they are thought to mediate cancer risk via insulin resistance and obesity. Given the potentially detrimental role for hyperinsulinaemia in both diabetes and cancer, physical activity is known to improve insulin sensitivity, particularly a combination of cardio-respiratory and resistance training.
Tobacco Smoking is more common in people with type 2 diabetes, and is well known to be associated with an increased risk of a number of cancers.
Socioeconomic status: social disadvantage carries a markedly increased risk of both type 2 diabetes, obesity and cancer, an effect probably mediated by modifiable behavioural risk factors
Medication: a number of medications have been claimed to increase (e.g. pioglitazone and bladder cancer) or reduce (e.g. aspirin and bowel cancer) cancer risk. Metformin is of particular interest in this respect [link].
Potentially modifiable environmental and/or behavioural risk factors play a predominant role in determining the risk of type 2 diabetes and of many types of cancer. This opens the way to future strategies of prevention.
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^ Clark AM, Raine K, Pahpael D. The American Cancer Society,American Diabetes Association and American Heart Association Joint Statement on preventing cancer, cardiovascular disease and diabetes: where are the social determinants? Diabetes Care 2004;27:3024.