Poor Metabolic Health Increased Risk for Colorectal Cancer in Women

Normal-weight women should be evaluated for metabolic health to reduce their risk for colorectal cancer, according to the results of a study published in Cancer Epidemiology, Biomarkers & Prevention.

Results from the study showed that almost one-third of normal-weight women had metabolically unhealthy phenotypes and that these phenotypes were associated with a higher risk for colorectal cancer.

“The results of this long-term prospective study of normal-weight postmenopausal women suggest that metabolically unhealthy women have a higher risk of colorectal cancer than metabolically healthy women,” wrote Xiaoyun Liang, MD, PhD, an associate professor at Beijing Normal University in China, and colleagues. “The reason why colorectal cancer risk is higher in normal-weight women with metabolic abnormalities is not entirely clear, but mechanistically, these results may suggest that the phenotype represents a proinflammatory state.”

Using data from the Women’s Health Initiative, the researchers analyzed 5,068 postmenopausal women with a body mass index between 18.5 and 25 kg/m². They sought to compare the risk for colorectal cancer in normal-weight postmenopausal women with healthy or unhealthy metabolic phenotypes.

Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference. Women were considered to be metabolically healthy if they had one or none of four components: elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and elevated fasting glucose.

Of the enrolled women, 33.7% had metabolically unhealthy phenotypes. These women were more likely to be older; non-Hispanic white; current smokers; have lower alcohol consumption, total energy intake, and dietary fiber; and less physical activity.

During the follow-up period, 114 cases of colorectal cancer occurred in 64 of the 3,358 metabolically healthy women and 50 of the 1,710 metabolically unhealthy women. Women with metabolically unhealthy phenotypes had a significantly greater risk for colorectal cancer compared with women with healthy phenotypes (hazard ratio [HR], 1.49; 95% CI, 1.02–2.18).

“Compared with metabolically healthy normal-weight individuals, metabolically unhealthy normal-weight individuals may have less physical activity and consume more saturated fat and less fiber; however, physical activity, saturated fat, and dietary fiber were included as covariates in this study, and it is unlikely that the differences in these lifestyle factors would account for the observed association,” the researchers wrote.

The researchers looked at the individual components of metabolic syndrome and found that elevated fasting glucose was associated with a significantly increased risk for colorectal (HR, 1.71; 95% CI, 1.12–2.58) and colon cancer (HR, 1.68; 95% CI, 1.04–2.71). Elevated triglycerides, low HDL cholesterol, and elevated blood pressure were not associated with colorectal or colon cancer.

Finally, women with metabolic syndrome had more than double the risk for colorectal (HR, 2.14; 95% CI, 1.38–3.32) and colon cancer (HR, 2.42; 95% CI, 1.48–3.95) compared with women who were metabolically healthy.

“Current guidelines recommend commencing colorectal cancer screening based primarily on age,” the researchers wrote. “Earlier identification of individuals at higher risk based on obesity or high-risk metabolic phenotype could result not only in appropriate preventive interventions, but also earlier screening thus increased likelihood of early-stage diagnosis and improved survival.”