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  • Gu, Fangyi, et al. (författare)
  • Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
  • 2010
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2877-2887
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background:</strong> 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.</p><p><strong>Methods:</strong> 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 &gt;5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.</p><p><strong>Results:</strong> After adjusting for multiple testing, SNPs in the <em>IGF1</em> and <em>SSTR5</em> genes were significantly associated with circulating IGF-I (<em>P</em> &lt; 2.1 × 10<sup>−4</sup>); SNPs in the <em>IGFBP3</em> and <em>IGFALS</em> genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained <em>R</em><sup>2</sup> = 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.</p><p><strong>Conclusion:</strong> Common genetic variation in the <em>IGF1</em> and <em>SSTR5</em> genes seems to influence circulating IGF-I levels, and variation in <em>IGFBP3</em> and <em>IGFALS</em> 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.</p><p><strong>Impact:</strong> Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.</p>
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