Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m² ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.

Background

Obesity is a strong risk factor for endometrial cancer, but it is unclear whether metabolic syndrome (MetS) contributes to endometrial cancer risk over and above the contribution of obesity.

Methods

We examined the association of MetS and its components with risk of endometrial cancer in a sub-cohort of 24,210 women enrolled in the Women's Health Initiative cohort study. Two variants of the National Cholesterol Education Program Adult Treatment Panel III definition of the MetS were used: one including and one excluding waist circumference (WC). Cox proportional hazards models were used to estimate the association of the study exposures with disease risk.

Results

When WC was included in the definition, MetS showed an approximately two-fold increase in endometrial cancer risk (HR 2.20; 95% CI 1.61-3.02); however, when WC was excluded, MetS was no longer associated with risk. We also observed that women with hyperglycemia, dyslipidemia and hypertension, in combination, had almost a twofold increased risk of endometrial cancer, independent of WC (HR 1.94; 95% CI 1.09, 3.46). Glucose, and, in particular, WC and body mass index were also positively associated with risk.

Conclusions

Our findings suggest that MetS may predict risk of endometrial cancer independent of obesity among women with the remaining four Mets components.