Affiliations of authors: F. B. Hu, Department of Nutrition, Harvard School of Public Health, Boston, MA; E. Giovannucci, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston.
Correspondence to: Frank B. Hu, M.D., Ph.D., Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115 (e-mail: frank.hu{at}channing.harvard.edu).
Ross suggested the increased oxidative stress because of hyperglycemia among diabetics as an additional mechanism for the observed positive association between type 2 diabetes mellitus and risk of colorectal cancer in women in our study. Although this is an interesting hypothesis, no data support a direct association between hyperglycemia and colorectal cancer. In our study, the positive association between diabetes and colon cancer was greatest within 11-15 years after diagnosis of diabetes and diminished after 15 years of diagnosis. These data suggest a more important role of hyperinsulinemia versus hyperglycemia, because hyperinsulinemia exists at an early stage of insulin resistance and diabetes but, as glucose intolerance worsens, intensified hyperglycemia and depletion of ß cells may lead to hypoinsulinemic response. Also, evidence exists that hyperinsulinemia increases risk of colon cancer by directly promoting colon carcinogenesis and stimulating insulin-like growth factor-I (IGF-I) (1,2) and that IGF-I levels significantly predict the risk of colorectal cancer (3).
REFERENCES
1 Koenuma M, Yamori T, Tsuruo T. Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26. Jpn J Cancer Res 1989;80:51-8.[Medline]
2 Tran TT, Medline A, Bruce WR. Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev 1996;5:1013-5.[Abstract]
3
Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens
CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like
growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 1999;91:620-5.
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