BACKGROUND: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I. MATERIALS AND METHODS: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden (CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort (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 IGF-I gene in relation to circulating IGF-I levels. RESULTS: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC (P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I (P = 0.001 and P < 0.0001, respectively). CONCLUSIONS: Genetic variation in the 3' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.
BACKGROUND: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I. MATERIALS AND METHODS: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden (CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort (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 IGF-I gene in relation to circulating IGF-I levels. RESULTS: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC (P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I (P = 0.001 and P < 0.0001, respectively). CONCLUSIONS: Genetic variation in the 3' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.
Authors: Fredrick R Schumacher; Iona Cheng; Matthew L Freedman; Lorelei Mucci; Naomi E Allen; Michael N Pollak; Richard B Hayes; Daniel O Stram; Federico Canzian; Brian E Henderson; David J Hunter; Jarmo Virtamo; Jonas Manjer; J Michael Gaziano; Laurence N Kolonel; Anne Tjønneland; Demetrius Albanes; Eugenia E Calle; Edward Giovannucci; E David Crawford; Christopher A Haiman; Peter Kraft; Walter C Willett; Michael J Thun; Loïc Le Marchand; Rudolf Kaaks; Heather Spencer Feigelson; H Bas Bueno-de-Mesquita; Domenico Palli; Elio Riboli; Eiliv Lund; Pilar Amiano; Gerald Andriole; Alison M Dunning; Dimitrios Trichopoulos; Meir J Stampfer; Timothy J Key; Jing Ma Journal: Hum Mol Genet Date: 2010-05-19 Impact factor: 6.150
Authors: Fangyi Gu; Fredrick R Schumacher; Federico Canzian; Naomi E Allen; Demetrius Albanes; Christine D Berg; Sonja I Berndt; Heiner Boeing; H Bas Bueno-de-Mesquita; Julie E Buring; Nathalie Chabbert-Buffet; Stephen J Chanock; Françoise Clavel-Chapelon; Vanessa Dumeaux; J Michael Gaziano; Edward L Giovannucci; Christopher A Haiman; Susan E Hankinson; Richard B Hayes; Brian E Henderson; David J Hunter; Robert N Hoover; Mattias Johansson; Timothy J Key; Kay-Tee Khaw; Laurence N Kolonel; Pagona Lagiou; I-Min Lee; Loic LeMarchand; Eiliv Lund; Jing Ma; N Charlotte Onland-Moret; Kim Overvad; Laudina Rodriguez; Carlotta Sacerdote; Maria-José Sánchez; Meir J Stampfer; Pär Stattin; Daniel O Stram; Gilles Thomas; Michael J Thun; Anne Tjønneland; Dimitrios Trichopoulos; Rosario Tumino; Jarmo Virtamo; Stephanie J Weinstein; Walter C Willett; Meredith Yeager; Shumin M Zhang; Rudolf Kaaks; Elio Riboli; Regina G Ziegler; Peter Kraft Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-09-01 Impact factor: 4.254
Authors: Sally L Ricketts; Katrijn L Rensing; Jeff M Holly; Li Chen; Elizabeth H Young; Robert Luben; Sofie Ashford; Kijoung Song; Xin Yuan; Abbas Dehghan; Benjamin J Wright; Dawn M Waterworth; Vincent Mooser; Gérard Waeber; Peter Vollenweider; Stephen E Epstein; Mary S Burnett; Joseph M Devaney; Hakon H Hakonarson; Daniel J Rader; Muredach P Reilly; John Danesh; Simon G Thompson; Alison M Dunning; Cornelia M van Duijn; Nilesh J Samani; Ruth McPherson; Nicholas J Wareham; Kay-Tee Khaw; S Matthijs Boekholdt; Manjinder S Sandhu Journal: Int J Mol Epidemiol Genet Date: 2011-08-03
Authors: Elena E Giorgi; Daniel O Stram; Darin Taverna; Stephen D Turner; Fredrick Schumacher; Christopher A Haiman; Annette Lum-Jones; Maarit Tirikainen; Christian Caberto; David Duggan; Brian E Henderson; Loic Le Marchand; Iona Cheng Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-06-05 Impact factor: 4.254
Authors: Federico Canzian; David G Cox; V Wendy Setiawan; Daniel O Stram; Regina G Ziegler; Laure Dossus; Lars Beckmann; Hélène Blanché; Aurelio Barricarte; Christine D Berg; Sheila Bingham; Julie Buring; Saundra S Buys; Eugenia E Calle; Stephen J Chanock; Françoise Clavel-Chapelon; John Oliver L DeLancey; W Ryan Diver; Miren Dorronsoro; Christopher A Haiman; Göran Hallmans; Susan E Hankinson; David J Hunter; Anika Hüsing; Claudine Isaacs; Kay-Tee Khaw; Laurence N Kolonel; Peter Kraft; Loïc Le Marchand; Eiliv Lund; Kim Overvad; Salvatore Panico; Petra H M Peeters; Michael Pollak; Michael J Thun; Anne Tjønneland; Dimitrios Trichopoulos; Rosario Tumino; Meredith Yeager; Robert N Hoover; Elio Riboli; Gilles Thomas; Brian E Henderson; Rudolf Kaaks; Heather Spencer Feigelson Journal: Hum Mol Genet Date: 2010-07-15 Impact factor: 6.150
Authors: Prevathe Poniah; Zahurin Mohamed; Yamunah Devi Apalasamy; Shamsul Mohd Zain; Shanggar Kuppusamy; Azad Ha Razack Journal: Int J Clin Exp Med Date: 2015-10-15
Authors: Martijn Verheus; Gertraud Maskarinec; Christy G Woolcott; Christopher A Haiman; Loïc Le Marchand; Brian E Henderson; Iona Cheng; Laurence N Kolonel Journal: Int J Cancer Date: 2010-09-01 Impact factor: 7.396