Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density
2008 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 112, no 1, 109-122 p.Article in journal (Refereed) Published
INTRODUCTION: High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. OBJECTIVES: We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. DESIGN AND METHODS: Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. RESULTS: The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and higher. CONCLUSION: Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.
Place, publisher, year, edition, pages
2008. Vol. 112, no 1, 109-122 p.
insulin-like growth factor I, SNP, circulating levels, breast density, menopause, prospective study, Prospect-EPIC
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-18666DOI: 10.1007/s10549-007-9827-xISI: 000259696500014PubMedID: 18064566OAI: oai:DiVA.org:umu-18666DiVA: diva2:174315