Insulin-like Growth Factor I (IGF-I), IGF-binding Proteins, and Breast Cancer

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 11; no. 12; pp. 1566 - 1573
• Main Authors: KRAJCIK, Rozlyn A, BOROFSKY, Nancy D, MASSARDO, Stephen, ORENTREICH, Norman
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2002
• Subjects: Adult; Age Distribution; Aged; Biological and medical sciences; Biomarkers - blood; Breast Neoplasms - epidemiology; Breast Neoplasms - etiology; Breast Neoplasms - physiopathology; Case-Control Studies; Cohort Studies; Female; Gynecology. Andrology. Obstetrics; Humans; Incidence; Insulin-Like Growth Factor Binding Proteins - adverse effects; Insulin-Like Growth Factor I - adverse effects; Logistic Models; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Odds Ratio; Postmenopause; Premenopause; Prognosis; Reference Values; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis; Tumors; Human; Mammary gland diseases; Binding protein; Risk factor; Female; Mammary gland; Malignant tumor; Insulin like growth factor 1; Epidemiology
• ISSN: 1055-9965; 1538-7755

Epidemiological evidence supports a role for the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the induction and progression of various cancers. Estrogen, which plays a role in the etiology of breast cancer, both regulates and is influenced by the IGF family. Risk of breast cancer associated with serum levels of IGF-I and/or IGFBPs may therefore depend upon menopausal status. A nested, case-control study was conducted on 66 women who were premenopausal and 60 who were postmenopausal at the time of diagnosis of primary breast cancer; they were selected from a cohort of 95,000 women who underwent multiphasic health check-ups > 30 years ago when enrolled in the Kaiser Permanente Medical Care Program. For each case, one control who matched by age, date of examination, and length of follow-up was chosen. Concentrations of IGF-I, insulin, glucose, and IGFBP-1, IGFBP-2, and IGFBP-3 in serum drawn at least 2 years before diagnosis (mean times of 10.5 and 15.8 years for pre- and postmenopausal cases, respectively) were compared using conditional logistic regression analysis. All statistical tests were two-sided. Serum IGF-I, adjusted for insulin, glucose, and body mass index, was weakly associated with breast cancer risk across quartiles for premenopausal women only ( P for trend = 0.05). Serum IGFBP-3 was higher in premenopausal cases versus controls ( P = 0.04) and showed a positive trend in risk for increasing quartiles ( P for trend = 0.033). After adjusting for insulin, glucose, body mass index, and IGF-I, premenopausal women in the highest quartile of IGFBP-3 had an elevated risk of breast cancer [odds ratio (OR) = 5.28, 95% confidence interval (CI) = 1.13–24.7]. Conversely, IGFBP-3 was lower in postmenopausal cases versus controls ( P = 0.04) but showed no significant trend in risk. Postmenopausal women with glucose levels in the diabetic range were at increased risk for developing breast cancer (OR = 2.06, 95% CI = 0.87–4.91), whereas those in the highest quartile of IGFBP-2 had a substantial reduction (71%) in risk relative to those in the lowest quartile (OR = 0.29, 95% CI = 0.09–0.92). Serum IGFBP-1 was not associated with breast cancer risk in either pre- or postmenopausal women. In premenopausal women, elevated serum IGF-I and IGFBP-3 are associated with increased breast cancer risk, whereas elevated serum IGFBP-2 is inversely associated with risk of postmenopausal breast cancer.