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Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115 [E. G., W. C. W., M. J. S., G. A. C., F. E. S., S. E. H.]; Departments of Nutrition [E. G., E. A. P., W. C. W., M. J. S.] and Epidemiology [E. G., E. A. P., W. C. W., M. J. S., G. A. C. S. E. H.], Harvard School of Public Health, Boston, Massachusetts 02115; and Cancer Prevention Research Unit, Departments of Medicine and Oncology, Jewish General Hospital and McGill University, Montreal, Quebec, H3T 1E2 Canada [M. N. P., N. M.]
Insulin-like growth factor-1 (IGF-1) is an important mitogen, and IGF
binding protein-3 (IGFBP-3) has opposing effects. Acromegalics, who
have abnormally elevated levels of IGF-1, are at increased risk of
colorectal tumors. Recent studies have found that IGF-1 levels
correlate with risk of prostate cancer and colorectal cancer in men,
premenopausal breast cancer in women, and lung cancer in men and women.
We examined whether prediagnostic plasma levels of IGF-1 and IGFBP-3
influence risk of colorectal cancer and adenoma in women. From 1989 to
1990, a total of 32,826 women from the Nurses’ Health Study provided
blood specimens that were archived in liquid nitrogen. During 6 years
of follow-up from 1989 to 1994, we documented 79 new cases of
colorectal cancer, 90 cases of intermediate/late-stage adenoma (
1 cm
or tubulovillous/villous histology), and 107 cases of early-stage
adenoma (<1 cm and tubular histology). After matching controls (2:1
for cancers and 1:1 for adenomas) to cases by age, month of blood draw,
fasting status, and indication for endoscopy (for adenoma controls),
plasma IGF-1 and IGFBP-3 levels were measured. Controlling for IGFBP-3
level, relative to women in the low tertile of IGF-1, those in the high
tertile were at elevated risk of intermediate/late-stage colorectal
neoplasia adenoma [multivariate relative risk (RR), 2.78; 95%
confidence interval (CI), 0.76–9.76] and cancer (RR, 2.18; 95% CI,
0.94–5.08). Controlling for IGF-1 level, relative to women in the low
tertile of IGFBP-3, women in the high tertile of IGFBP-3 were at lower
risk of intermediate/late-stage colorectal adenoma (RR, 0.28; 95% CI,
0.09–0.85) and cancer (RR, 0.28; 95% CI, 0.10–0.83). Neither IGF-1
nor IGFBP-3 had any appreciable relation with early-stage adenoma.
These analyses indicate that high levels of circulating IGF-1 and
particularly low levels of IGFBP-3 are associated independently with an
elevated risk of large or tubulovillous/villous colorectal adenoma and
cancer.
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