title: Premenopausal levels of circulating insulin-like growth factor I and the risk of postmenopausal breast cancer.
abstract: Increased levels of insulin-like growth factor I (IGF-I) may directly stimulate breast cell proliferation and promote growth and survival of transformed cells. Higher levels of IGF-I have been associated with increased risk of premenopausal breast cancer but not postmenopausal breast cancer. We investigated whether circulating levels of IGF-I prior to menopause are associated with breast cancer diagnosed after menopause in a population-based nested case-control study. Female cohort participants were enrolled in 1974 (n = 15,192) and 1989 (n = 18,724) and blood was drawn. Cases were women diagnosed with primary breast cancer at ages > or =50, of whom 152 were premenopausal at blood draw. One control was matched to each case on cohort participation, age, ethnic group, menopausal status and date of blood draw. Levels of IGF-I and IGF binding protein 3 (IGFBP-3) were measured using enzyme-linked immunoabsorbent assays. The association between IGF-I and breast cancer was determined using conditional logistic regression, adjusting for IGFBP-3. IGF-I levels decreased with age (p = 0.0001). Prior to age-stratification, IGF-I levels neither measured before nor after menopause were associated with postmenopausal breast cancer. After age-stratification, associations were suggested in the youngest premenopausal age group (upper vs. lowest third: odds ratio (OR) = 5.31, 95% confidence intervals (CI) = 0.85-33.13; p trend = 0.06) and oldest postmenopausal age group (upper vs. lowest third: OR = 3.41, 95% CI = 0.66-17.71; p trend = 0.13). The association between circulating levels of IGF-I and postmenopausal breast cancer risk may be modified by age. Increased levels of circulating IGF-I may be of particular interest in the younger premenopausal women and older postmenopausal women. Age-stratification should be undertaken in larger investigations of IGF-I levels as predictors of postmenopausal breast cancer.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E-6142, Baltimore, MD 21205, USA.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rollison
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Newschaffer
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Tao
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology; D004198:Disease Susceptibility / Q000097:blood*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D017697:Premenopause / Q000097:blood*; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I