Differences in IGFBP-3 regulation between young healthy women from BRCAX families and those belonging to BRCA1/2 families

Abstract

Since IGF-1 and IGFBP-3 levels have been implicated in premenopausal breast cancer, we aimed to explore whether there were differences in IGF-1 and IGFBP-3 regulation between women from BRCA1/2 families and from families in which no BRCA1/2 mutations could be detected, that is, from BRCAX families. One hundred and one healthy 18-40-year-old women from hereditary breast cancer families with known BRCA1/2 mutations and 111 women from BRCAX families completed a questionnaire including information on reproductive factors and oral contraceptive use. We measured height, weight, and plasma IGF-1 and IGFBP-3 levels during menstrual cycle days 5-10 and again during cycle days 18-23. IGF1 and IGFBP3 genotypes were determined. Women from BRCAX families had higher IGFBP-3 levels than women from BRCA1/2 families during cycle days 5-10 (P=0.08) and cycle days 18-23 (P=0.0001). The IGFBP3 (A-202C) A allele also segregated at a significantly higher frequency among women from BRCAX families than among women from BRCA1/2 families (40.3 versus 30.3%; P=0.04). The IGFBP3 genotype was highly associated with the IGFBP-3 levels during cycle days 5-10 and 18-23 (Ptrend=0.0004 and Ptrend=0.0003, respectively). After taking the IGFBP3 genotype into account, IGFBP-3 levels were still significantly higher in women from BRCAX families during cycle days 18-23 (P=0.004). No differences were found in IGF1 genotype or IGF-1 levels or the ratio of IGF-1 to IGFBP-3 between women from BRCAX and BRCA1/2 families. In conclusion, we found significant differences in IGFBP-3 regulation between young healthy women from BRCAX families and those belonging to BRCA1/2 families. It is possible that a subgroup of the BRCAX families has an increased risk of breast cancer because of high IGFBP-3 levels.