© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 12, 914-916,
June 18, 2003
© 2003 Oxford University Press
BRIEF COMMUNICATION |
Glycemic Load, Carbohydrate Intake, and Risk of Colorectal Cancer in Women: A Prospective Cohort Study
Affiliations of authors: P. D. Terry, T. E. Rohan, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY; M. Jain, Integrated Policy and Planning Division, Ontario Ministry of Health and Long-Term Care, and Department of Public Health Sciences, University of Toronto, Toronto, Canada; A. B. Miller, Department of Public Health Sciences, University of Toronto, and Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany; G. R. Howe, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
Correspondence to: Paul D. Terry, Ph.D., M.P.H., National Institute of Environmental Health Sciences, Epidemiology Branch, P.O. Box 12233 MD A3–05, Research Triangle Park, NC 27709–2233 (e-mail: terry2{at}niehs.nih.gov).
ABSTRACT
Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk. The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and/or insulin-like growth factor-I levels. We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a randomized, controlled trial of screening for breast cancer in Canada. Linkages to Canadian mortality and cancer databases yielded data on mortality and cancer incidence up to December 31, 2000. During an average 16.5 years of follow-up, we observed 616 incident cases of colorectal cancer (436 colon cancers, 180 rectal cancers). Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 (95% confidence interval [CI] = 0.73 to 1.53; Ptrend = .94) for glycemic load, 1.01 (95% CI = 0.68 to 1.51; Ptrend = .66) for total carbohydrates, and 1.03 (95% CI = 0.73 to 1.44; Ptrend = .71) for total sugar. Our data do not support the hypothesis that diets high in glycemic load, carbohydrates, or sugar increase colorectal cancer risk.
Diet is a potentially modifiable exposure that might be associated with colorectal cancer risk (1). In this regard, carbohydrates may be particularly relevant because they have postprandial glycemic effects and can therefore affect insulin levels (2–4). Mounting evidence from epidemiologic, clinical, and experimental studies suggests that relatively high circulating levels of insulin might be associated with increased colorectal cancer risk (4–7). The glycemic index is a means of classifying the carbohydrate content of individual foods according to their postprandial glycemic effects and, hence, their effects on blood insulin levels (2–4). Thus, the total glycemic effect (i.e., glycemic load) can be estimated with respect to a given diet (8). Only two previous studies (9,10), both of which used case–control designs, have examined the association between glycemic load and the risk of colorectal cancer. One study (10) found 69% and 87% increased colon cancer risk among females and males, respectively, who consumed diets with a high glycemic load compared with those who consumed diets with a low glycemic load; associations with dietary sugar intake in that study were generally weaker than those with glycemic load or null. The other study (9) found that individuals with a high glycemic load had a 70% increased risk of colorectal cancer compared with those with a low glycemic load. However, case–control studies are susceptible to selection and recall bias. Therefore, in the large prospective cohort study reported here, we examined the association between dietary glycemic load, intakes of carbohydrates and sugar, and subsequent colorectal cancer risk in women.
The design of our study has been described in detail elsewhere (11). In brief, 89 835 women aged 40–59 years were recruited into the Canadian National Breast Screening Study from the general Canadian population between 1980 and 1985 (12,13). Information was obtained from participants on demographic characteristics, lifestyle factors, menstrual and reproductive histories, and the use of oral contraceptives and hormone replacement therapy. Beginning in 1982, a questionnaire regarding diet and physical activity was distributed to all new attendees at all screening centers and to women returning to the screening centers for re-screening (14). A total of 49 612 dietary questionnaires were returned and were available for analysis. We excluded 422 women from our study because they had extreme energy intake values (at least three standard deviations above or below the mean value for natural logarithm-transformed calories), and we excluded 66 women with prevalent colorectal cancer. Thus, the study cohort comprised 49 124 women at the start of follow-up.
We used glycemic index values for foods that were obtained from published reports of studies conducted in North America (8). The total dietary glycemic load was calculated by multiplying the carbohydrate intake from a particular food item by its glycemic index value and summing the resulting values for all food items reported. When the reported glycemic index values for a particular food item varied across studies (8), we used the mean of the reported values of glycemic index for that food item. The main foods contributing to glycemic load in our study cohort are listed in a footnote to Table 1
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Outcome (incident colorectal cancer or death) was ascertained by computerized record linkages to the Canadian Cancer Database and the National Mortality Database, both of which are maintained by Statistics Canada. Linkages to these databases yielded data on mortality and cancer incidence up to December 31, 2000, for women who resided in Ontario; to December 31, 1998, for women who resided in Quebec; and to December 31, 1999, for women who resided in other regions of Canada. During follow-up of the dietary cohort, we identified 616 incident cases of colorectal cancer (436 colon cancers and 180 rectal cancers). Cox proportional hazards models (using duration of follow-up as the time scale) were used to estimate rate ratios and 95% confidence intervals (CIs) for the association between glycemic load and colorectal cancer risk. We examined the proportional hazards assumption by including time-varying covariates in the model and by plotting the log of the cumulative hazards function. There was no violation of the proportional hazards assumption. Multivariable models included the variables listed in a footnote to Table 2
. For tests of trend in risk across successive levels of categorical variables, median values of each category were fitted in the risk models as successive integers (15). Tests for interaction were based on likelihood ratio tests that compared models with and without product terms representing the variables of interest. All P values are two-sided.
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The average duration of follow-up for cohort members was 16.5 years, which corresponded to a total of 810 649 person-years of follow-up. The average age (± standard deviation) at diagnosis was 62.0 years (±7.1 years) for case subjects who developed colon cancer and 60.4 years (±7.1 years) for case subjects who developed rectal cancer. There was a 2.6-fold difference in median values between the lowest and the highest quintiles of glycemic load (Table 1
). Compared with women who had low glycemic load, women with high glycemic load were slightly older, engaged in more physical activity, consumed less alcohol, had higher intakes of energy and red meat, were less likely to have smoked, were less likely to have attended a university, and were slightly more likely to have used hormone replacement therapy. There was no appreciable variation in median body mass index, calcium or folic acid intake, or parity by quintile levels of glycemic load.
Glycemic load was not associated with colorectal cancer risk after adjustment for age and energy intake only (data not shown) or in multivariable-adjusted models (Table 2). There was also no association between colorectal cancer risk and intake of total carbohydrates or sugars (including sucrose, glucose, fructose, and other types of sugar, when analyzed separately [data not shown]). Although there was a suggestion of positive associations between glycemic load and carbohydrate intake and the risk of distal colon cancer, those findings were based on a limited number of cases. The null associations with these dietary factors were unaltered after we excluded cases that were diagnosed within the first year of follow-up, suggesting that changes in diet due to preclinical undiagnosed colorectal cancer were unlikely to have influenced the results. The associations between glycemic load and proximal or distal colorectal cancers did not vary appreciably across strata defined by total fiber; fiber from cereals, fruits, or vegetables; physical activity levels; body mass index; or menopausal status (data not shown).
Our data are limited by the possibility of error with respect to the measurement of diet and the calculation of glycemic load. In our study, misclassification may have resulted from errors in the measurement of daily intake of carbohydrates and sugars because of inaccurate recall or changes in diet over time (16). Misclassification also could have arisen because glycemic index values derived from studies that considered food items separately may not accurately reflect the glycemic index values of those foods when they are consumed with other foods, that is, the absorption and metabolism of individual foods may be altered as a result of their consumption with other foods (17). In addition, the glycemic index values of some foods are currently based on results reported in only one or two studies, and those studies often had small sample sizes (8). Thus, misclassification in our study could also be caused by random variation in the estimated values of glycemic index. Finally, although we adjusted our estimates for a wide range of potentially confounding variables, uncontrolled confounding from dietary (or other) factors cannot be excluded.
In conclusion, our data do not support the hypothesis that diets high in glycemic load, carbohydrates, or sugar increase colorectal cancer risk.
NOTES
Funded in part by the National Cancer Institute of Canada.
We thank Statistics Canada, the provincial and territorial Registrars of Vital Statistics, and the Cancer Registry directors for their assistance in making the cancer incidence and mortality data available.
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Manuscript received December 18, 2002; revised April 4, 2003; accepted April 16, 2003.
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