IGF1, IGFBP1, and IGFBP3 genes and mammographic density: the Multiethnic Cohort

Insulin-like growth factor-I (IGF-I) has mitogenic properties and stimulates cell growth. In this analysis, we investigated the relation between common genetic variation in IGF1, IGFBP1, and IGFBP3, and mammographic density among 819 women of Hawaiian, European, and Japanese ancestry from the Multiethnic Cohort Study. Mammographic density was assessed using a quantitative computer-assisted method. Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (26 tag SNPs) and IGFBP1/IGFBP3 (22 tag SNPs) were genotyped among the 819 women. Mixed models were conducted to evaluate the associations between genetic variation and mammographic density. Two SNPs were borderline statistical significantly associated with mammographic density: rs35539615 on IGFBP1 (p = 0.05) and rs2453839 on IGFBP3 (p = 0.01). Rs35767on IGF1 (p = 0.03) was also associated with mammographic density, although in opposite direction of what was expected from previous findings with IGF-I levels. The majority of SNPs were, however, not associated with mammographic density. Analyses stratified by ethnicity showed similar results as the overall analyses for IGF1 and IGFBP1. However, for 4 SNPs in the IGFBP3 gene, the minor allele was associated with lower mammographic density in Japanese Americans and higher mammographic density in Caucasians. Given the large number of SNPs tested and the few borderline significant results, we only found weak evidence that genetic variations in IGFBP1 or IGFBP3 may be related to mammographic density. Ethnicity may modify these relations.