Insulin resistance and cancer: epidemiological evidence

Abstract

Over the last 60 years, Japanese people have experienced a rapid and drastic change in lifestyle, including diet. Suspicions have been raised that so-called 'Westernization', characterized by a high-calorie diet and physical inactivity, is associated with increasing trends in the incidence of cancer of the colon, liver, pancreas, prostate, and breast, as well as type 2 diabetes. Epidemiological evidence from our prospective study, the Japan Public Health Center-based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers. These cancers are inversely associated with physical activity and coffee consumption, which are known to decrease the risk of type 2 diabetes. The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin-like growth factor 1 (IGF1) stimulate tumor growth. In contrast, associations with diabetes are less clear for cancer of the colon in women, and breast and prostate, which are known to be related to sex hormones. The effect of insulin resistance or body fat on sex-hormone production and bioavailability may modify their carcinogenic effect differently from cancers of the colon in men, and liver and pancreas. In conclusion, there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption.

Figure 1

Time trends in nutrient intake (per capita per day) in Japan. Data source: The National Nutrition Survey by the Ministry of Health, Labour and Welfare of Japan.

Figure 2

Trends in mortality rates of selected cancers in Japan (rate adjusted by Japanese model population in 1985). Data source: Vital Statistics Reports by the Ministry of Health, Labour and Welfare of Japan.

Figure 3

History of diabetes and risk of cancer: the Japan Public Health Center‐based Prospective (JPHC) study. Adjusted for age, study area, history of cerebrovascular disease, history of ischemic heart disease, smoking, ethanol intake, body mass index, leisure‐time physical activity, green vegetable intake, and coffee intake. Data source: Inoue et al. ^{( 12 )}

Figure 4

Plasma C‐peptide and risk of colon cancer: a nested case control study within the Japan Public Health Center‐based Prospective (JPHC) Study. Matched by sex, age, date of blood drawn, time since last meal, and study area. Adjusted for smoking, ethanol intake, body mass index, leisure‐time physical activity, and family history of colorectal cancer. Data source: Otani et al. ^{( 22 )}

Figure 5

Physical activity and cancers of the colon, liver, and pancreas: the Japan Public Health Center‐based Prospective (JPHC) study. HR, hazard ratio. Data source: Inoue et al. ^{( 29 )}

Figure 6

Coffee consumption and cancers of the colon, liver, and pancreas: the Japan Public Health Center‐based Prospective (JPHC) study. HR, hazard ratio. Data sources: colon;^{( 33 )} liver;^{( 32 )} pancreas.^{( 34 )}