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Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density
- Verheus, Martijn (författare)
- McKay, James D (författare)
- Kaaks, Rudolf (författare)
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- Canzian, Federico (författare)
- Biessy, Carine (författare)
- Grobbee, Diederick E (författare)
- Peeters, Petra H M (författare)
- van Gils, Carla H (författare)
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- (creator_code:org_t)
- 2007-12-07
- 2008
- Engelska.
- Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 112:1, s. 109-122
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- insulin-like growth factor I
- SNP
- circulating levels
- breast density
- menopause
- prospective study
- Prospect-EPIC
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Breast Cancer Research and Treatment (Sök värdpublikationen i LIBRIS)
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