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Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115
Dear Editor,
Studies that assess body mass index, physical inactivity, central adiposity or that measure insulin in relation to colon cancer risk, as well as animal studies, support the hypothesis that hyperinsulinemia increases the risk of colon cancer (1
). Studies also show that high circulating IGF-1 is associated with higher risk of colon cancer (1
). Although the mechanisms linking insulin and IGF-1 to colon cancer could be independent, the close relationship between these hormones suggests a common link. Hyperinsulinemia may increase bioactive or free IGF-1 by reducing levels of IGF binding proteins 1 and 2, while not influencing total IGF-1 level substantially (1
). Thus, factors that lower insulin, and thereby also lower free IGF-1, could be protective against colon cancer risk.
I argued that the most important nutritional factor determining insulin levels is probably energy balance (1
). Secondarily, some specific dietary factors, including refined carbohydrates and saturated and trans-fatty acids may have a role beyond their contribution to energy balance. The role of specific dietary factors is difficult to assess because of intercorrelated elements in the diet. Factor analysis, one approach attempting to integrate these factors, has identified a dietary pattern characterized by relatively higher consumption of red meat and processed meat, refined grains, sweets and lower consumption of whole grains and poultry (2
,3
). Factors associated with this dietary pattern are related to both high insulin levels (2
) and colon cancer risk (3
). It is presently impossible to determine which of the specific individual components of this dietary pattern are the most important determinants of its hyperinsulinemic effect.
As Grant argues in the accompanying letter, protein intake does influence IGF-1 level somewhat. However, IGF-1 level also has strong genetic determinants (4
). Except in relatively extreme conditions of protein and energy restriction, the dietary influence of IGF-1 may be relatively modest, although these relationships should be studied further. Protein and energy intakes during growth that are sufficiently low to limit attained height probably lower IGF-1 levels substantially, which may explain why average population height correlates with rates of some cancers, including colon cancer (1
). Meat availability is a good indicator of affluence. Thus, the ecologic data referred to by Grant supporting a role for animal protein are intractably confounded by factors associated with economic development including obesity, physical inactivity, highly refined carbohydrate diet and saturated fat, in addition to height. These data are important in demonstrating that a Western lifestyle is deleterious with respect to colon cancer risk, but to implicate protein intake in adulthood in isolation of other factors (e.g., obesity, physical inactivity or nutrition during development) is not possible.
In studies conducted within populations, for which confounding factors may be minimized and better controlled, red meat (perhaps processed meat in particular) is associated with a higher risk, but all other sources of protein are either not associated with risk or are associated with a lower risk. Although sources of protein may increase circulating IGF-1 slightly, they may also contribute potentially beneficial nutrients, including (n-3) fatty acids, calcium, methionine and have a low glycemic load. In the Health Professionals Follow-Up Study, for example, almost three fourths of colon cancer was attributable to modifiable factors (obesity, physical inactivity, red meat, alcohol and low folate) (5
), whereas higher total protein intake was related to a lower risk of colon cancer (6
). The major protein sources included fish, poultry and low fat dairy, in addition to plant sources. Focusing on obesity, physical inactivity and hyperinsulinemic aspects of diet, rather than total protein intake, is more likely to benefit overall health, including colon cancer risk, although avoiding some sources of protein may be prudent.
Manuscript received 19 February 2002. Revision accepted 28 February 2002.
LITERATURE CITED
1. Giovannucci, E. (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J. Nutr. 131:3109S-3120S.
2. Fung, T. T., Rimm, E. B., Spiegelman, D., Rifai, N., Tofler, G. H., Willett, W. C. & Hu, F. B. (2001) The association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am. J. Clin. Nutr. 73:61-67.
3. Slattery, M. L., Boucher, K. M., Caan, B. J., Potter, J. D. & Ma, K. N. (1998) Eating patterns and risk of colon cancer. Am. J. Epidemiol. 148:4-16.
4. Hong, Y., Pedersen, N. L., Brismar, K., Hall, K. & De Faire, U. (1996) Quantitative genetic analyses of insulin-like growth factor-I (IGF-I), IGF-binding protein-1, and insulin levels in middle-aged and elderly twins. J. Clin. Endocrinol. Metab. 81:1791-1797.[Abstract]
5. Platz, E. A., Willett, W. C., Colditz, G. A., Rimm, E. B., Spiegelman, D. & Giovannucci, E. (2000) Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men. Cancer Causes Control 11:579-588.[Medline]
6. Giovannucci, E., Rimm, E. B., Stampfer, M. J., Colditz, G. A., Ascherio, A. & Willett, W. C. (1994) Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res. 54:2390-2397.
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