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Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2877-87. doi: 10.1158/1055-9965.EPI-10-0507. Epub 2010 Sep 1.

Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer.

Author information

1
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Abstract

BACKGROUND:

Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.

METHODS:

We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.

RESULTS:

After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.

CONCLUSION:

Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.

IMPACT:

Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.

PMID:
20810604
PMCID:
PMC2989404
DOI:
10.1158/1055-9965.EPI-10-0507
[Indexed for MEDLINE]
Free PMC Article

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