High Glucose Levels Raise Colon Cancer Risk in Women

Tuesday, December 27, 2011
Older women who have high levels of serum glucose are at increased risk for colorectal cancer, a longitudinal study found.

Compared with postmenopausal women whose glucose levels were in the lowest tertile, those in the highest tertile had a multivariable adjusted hazard ratio for colorectal cancer of 1.74 (95% CI 0.97 to 3.15, P for trend=0.06), according to Geoffrey C. Kabat, MD, of Albert Einstein College of Medicine in New York, and colleagues.

And the risk was even higher when the analysis was specifically for colon cancer (HR 2.25, 95% CI 1.12 to 4.51, P for trend=0.02), they reported online in the British Journal of Cancer.
Action Points  
  • In this study, older women who had high levels of serum glucose were at increased risk for colorectal cancer.

  • Note that unlike glucose, baseline levels of insulin and the insulin resistance index were not associated with an increased risk of colorectal or colon cancer.

Although obesity and related conditions such as diabetes and the metabolic syndrome have been linked with colorectal cancer, it has not been known whether the risk relates to levels of circulating insulin or glucose.

Insulin theoretically could contribute in that it is anti-apoptotic and mitogenic, whereas glucose might increase the risk by providing an energy source for malignant cells, the researchers explained.

But the results of epidemiologic studies looking at a possible link between insulin and glucose levels have had inconsistent findings, possibly because of differences in types of study as well as in populations and risk factors.

So to examine this prospectively, Kabat and colleagues analyzed data from a subset of women participating in the Women's Health Initiative who had baseline and serial follow-up measurements of fasting serum glucose and insulin.

Covariates in the analysis included age, body mass index (BMI), alcohol consumption, physical activity, ethnicity, and family history of colorectal cancer.

During a median of 11.9 years, there were 81 cases of colorectal cancer among the cohort of 4,902 women.

A total of 65 of the cases were colon cancer, in six the malignancy was the rectosigmoid junction, and in 10 the cancer was rectal.

Compared with women who did not develop colorectal cancer, those who did were older by about two years, were more often white, and were less likely to be physically active.

Unlike glucose, which had a "robust" association, baseline levels of insulin and the insulin resistance index were not associated with an increased risk of colorectal or colon cancer, according to the researchers.

After mutual adjustment for glucose and insulin, the hazard ratio for the highest tertile of glucose versus the lowest was 1.72 (95% CI 0.94 to 3.15, P for trend=0.07), while the hazard ratio for insulin was 0.88 (95% CI 0.47 to 1.65, P for trend=0.70).

The hazard ratio for each 1 mg/dL−1 of glucose was 1.031 (95% CI 1.009 to 1.054, P for trend=0.0066).

The risk for both colorectal and colon cancer with higher levels of glucose was seen in patients whose BMI was 27.76 or higher, with a hazard ratio per mg/dL−1 of 1.029 (95% CI 0.997 to 1.062, P=0.08), and also for those whose BMI was lower (HR 1.031, 95% CI 1.001 to 1.063, P=0.04).

Here, too, the baseline insulin and the insulin resistance index were not associated with cancer risk.

The researchers also did the analysis excluding patients whose cancer developed within two years of study entry to eliminate possible cases of subclinical disease, and found similar results, with a hazard ratio for the highest versus lowest tertile of glucose of 1.81 (95% CI 0.93 to 3.51, P for trend 0.07).

"In conclusion," the researchers wrote, "in this cohort study of postmenopausal women, elevated fasting serum glucose, but not insulin or [the homeostasis model assessment of insulin resistance] was associated with roughly a twofold increased risk of colorectal cancer."

A limitation of the study was the small number of cancer cases identified and the researchers' resulting inability to more thoroughly analyze subsets of cases according to cancer sites and variables.

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