Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer.
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.
Krajcik
Rozlyn A
RA
Orentreich Foundation for the Advancement of Science, Inc, Cold Spring-on-Hudson, New York 10516, USA. ofas1@juno.com
Borofsky
Nancy D
ND
Massardo
Stephen
S
Orentreich
Norman
N
D000328:Adult; D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D018969:Insulin-Like Growth Factor Binding Proteins / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects*; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D017698:Postmenopause; D017697:Premenopause; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I