High Dietary Glycemic Load May Increase Colorectal Cancer Risk in Women

Mindy Hung

February 03, 2004

Feb. 3, 2004 — A diet with a high dietary glycemic load may increase the risk of colorectal cancer in women, according to results of a prospective cohort study published in the Feb. 4 issue of the Journal of the National Cancer Institute.

"The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth," write Susan Higginbotham and colleagues from the University of California at Los Angeles.

Investigators followed a cohort of 38,451 subjects from the Women's Health Study, aged 45 years or older at baseline, in April 1993 to January 1996. Researchers administered a 131-item semiquantitative food-frequency questionnaire at baseline to assess average dietary intake during the previous year.

Women with more than 70 blanks in the questionnaire, or those with a total daily energy intake of less than 2,514 kJ or more than 14,665 kJ were excluded. Subjects also filled out a risk factor questionnaire at baseline and annually thereafter.

Glycemic load was estimated for each woman by multiplying the glycemic load for each food by the frequency of consumption and then summing over all foods. They obtained the overall glycemic index (the average glycemic index of carbohydrates in the diet) by dividing the participant's dietary glycemic load by total carbohydrate intake. Glucose was the standard in calculating glycemic index and glycemic load values.

The researchers identified 174 patients with incident colorectal cancer (148 with cancer of the colon and 26 with cancer of the rectum). The mean dietary glycemic load for the cohort was 117, and the mean overall glycemic index was 53.

Statistically significant positive associations of both dietary glycemic load and overall glycemic index were seen with colorectal cancer in age-adjusted models. In multivariable analyses that included total energy intake and nutrient risk factors (fat, fiber, folate, calcium, and vitamin D) in the models, colorectal cancer risk estimates for dietary glycemic load increased (adjusted relative risk [RR], 2.85; 95% confidence interval [CI], 1.40 - 5.80, comparing extreme quintiles of dietary glycemic load; P = .004). However, overall glycemic index risk estimates were essentially unchanged (adjusted RR, 1.71; 95% CI, 0.98 - 2.98; P = .04, comparing extreme quintiles of overall glycemic index).

Risk estimates for total carbohydrate (adjusted RR, 2.41; 95% CI, 1.10 - 5.27, comparing extreme quintiles of carbohydrate; P = .02), nonfiber carbohydrate (corresponding RR, 2.60; 95% CI, 1.22 - 5.54; P = .02), sucrose (corresponding RR, 1.51; 95% CI, 0.90 - 2.54; P = .06), and fructose (corresponding RR, 2.09; 95% CI, 1.13 - 3.87; P = .08) were consistent with but lower than the dietary glycemic load findings.

Higginbotham and colleagues acknowledge risk factors such as body mass index, physical inactivity, smoking, alcohol use, and nutrient intake would most likely bias risk estimates toward the null, implying that true risk may be greater than their estimates.

They note that their research was also limited by the fact that when the glycemic index value of a particular food was unavailable, they used the reported value for a similar food.

"A diet with a high glycemic load may increase the risk of colorectal cancer by affecting insulin and insulin-like growth factors or, as suggested by the cross-sectional association between dietary glycemic load and C-reactive protein, by exacerbating proinflammatory responses, either locally or systemically," they write. "Further work is needed to elucidate these mechanisms."

The study was supported by grants from the National Institutes of Health.

J Natl Cancer Inst. 2004;96:229-233

Reviewed by Gary D. Vogin, MD

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