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  • 1. Johansson, Mattias
    et al.
    Mckay, James D.
    Stattin, Par
    Canzian, Federico
    Boillot, Catherine
    Wiklund, Fredrik
    Adami, Hans-Olov
    Bälter, Katarina
    Gronberg, Henrik
    Kaaks, Rudolf
    Comprehensive evaluation of genetic variation in the IGF1 gene and risk of prostate cancer2007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 3, p. 539-542Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF1) stimulates cell proliferation, decreases apoptosis, and has been implicated in cancer development. Epidemiological studies have shown elevated levels of circulating IGF1 to be associated with increased risk of prostate cancer. To what extent genetic variation in the IGF1 gene is related to prostate cancer risk is largely unknown. We performed a comprehensive haplotype tagging (HT) assessment of single nucleotide polymorphisms (SNPs) representing the common haplotype variation in the IGF1 gene. We genotyped 10 SNPs (9 haplotype tagging SNPs (htSNPs)) within Cancer Prostate in Sweden (CAPS), a case-control study of 2,863 cases and 1,737 controls, in order to investigate if genetic variation in the IGF1 gene is associated with prostate cancer risk. Three haplotype blocks were identified across the IGF1 gene and 9 SNPs were selected as haplotype tagging SNPs. Common haplotypes in the block covering the 3' region of the IGF1 gene showed significant global association with prostate cancer risk (p = 0.004), with one particular haplotype giving an odds ratio of 1.46 (95% CI = 1.15-1.84, p = 0.002). This haplotype had a prevalence of 5% in the study population. Our results indicate that common variation in the IGF1 gene, particularly in the 3' region, mail affect prostate cancer risk. Further studies on genetic variations in the IGF1 gene in relation to prostate cancer risk as well as to circulating levels of IGF1 are needed to confirm this novel finding. (c) 2006 Wiley-Liss. Inc.

  • 2. McKay, James D.
    et al.
    Kaaks, Rudolf
    Johansson, Mattias
    Biessy, Carine
    Wiklund, Fredik
    Bälter, Katarina
    Adami, Hans-Olov
    Boillot, Catherine
    Gioia-Patricola, Lydie
    Canzian, Federico
    Stattin, Par
    Gronberg, Henrik
    Haplotype-based analysis of common variation in the growth hormone receptor gene and prostate cancer risk2007In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 16, no 1, p. 169-173Article in journal (Refereed)
    Abstract [en]

    The growth hormone receptor (GHR) is potentially involved in prostate cancer through its role in stimulating insulin-like growth factor I production and its cellular effects on prostate epithelium. We have used a haplotype-based tagging approach within CAncer Prostate Sweden, a large retrospective case-control study of 2,863 cases and 1,737 controls to investigate if genetic variation in the GHR gene influences prostate cancer risk. One haplotype in the 3' region of the GHR gene was found associated with prostate cancer risk in elderly men (> 65 years old at the time of diagnosis), with heterozygote haplotype carriers having an odds ratio of 1.65 (95% confidence interval, 1.21-2.16; P = 0.0009, P-corrected = 0.03). GHR function has been implicated in the determination of body mass index. Interestingly, the same haplotype associated with risk in the 3' end of the GHR gene was also associated with a decrease in body mass index in controls (P = 0.003, P-corrected = 0.05), possibly indicating some functionality with this haplotype. These results suggest that whereas genetic variation in the GHR gene does not seem to play a major role in prostate cancer etiology, one haplotype in the 3' region may be potentially relevant to cases with later onset of prostate cancer.

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