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This version published online on October 2, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0887
A more recent version of this article appeared on December 1, 2007
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Submitted on April 18, 2007
Accepted on September 26, 2007

Implications for Prostate Cancer of IGF1 Genetic Variation and Circulating IGF1 Levels

Mattias Johansson*, James D. McKay, Fredrik Wiklund, Sabina Rinaldi, Martijn Verheus, Carla H. van Gils, Göran Hallmans, Katarina Bälter, Hans-Olov Adami, Henrik Grönberg, Pär Stattin, and Rudolf Kaaks

Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden; International Agency for Research on Cancer, Lyon, France; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands; Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden; Department of Epidemiology, Harvard University, Boston, MA, USA and Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

* To whom correspondence should be addressed. E-mail: Mattias.Johansson{at}oc.umu.se.

Background: Elevated levels of circulating IGF1 have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3' region of the IGF1 gene associated with increased risk of prostate cancer and we hypothesised that the observed association is mediated by circulating IGF1.

Material and methods: We analyzed haplotypes and 3 haplotype tagging SNPs (htSNPs) in the 3' region of the IGF1 gene in relation to circulating levels IGF1 in 698 control subjects from the CAPS study and 599 cases and controls from the prospective NSHDC study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3' region of the IGF1 gene in relation to circulating IGF1 levels.

Results: The IGF1 haplotype previously associated with prostate cancer risk, labelled "TCC", was associated with elevated levels of IGF1 in CAPS (p = 0.02), but not in NSHDC. In contrast, two of the three IGF1 htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF1 in NSHDC (p= 0.03 and 0.04, respectively), but not in CAPS. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF1 (p = 0.001 and <0.0001, respectively).

Conclusions: Genetic variation in the 3' region of the IGF1 gene seems to influence circulating levels of IGF1. This observation is consistent with the hypothesis that variation in the IGF1 gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF1.
Key words: IGF1 • plasma levels • single nucleotide polymorphism • haplotype • block




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C. Palles, N. Johnson, B. Coupland, C. Taylor, J. Carvajal, J. Holly, I. S. Fentiman, I. dos Santos Silva, A. Ashworth, J. Peto, et al.
Identification of genetic variants that influence circulating IGF1 levels: a targeted search strategy
Hum. Mol. Genet., May 15, 2008; 17(10): 1457 - 1464.
[Abstract] [Full Text] [PDF]


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