Interactions between genome-wide significant genetic variants and circulating concentrations of insulin-like growth factor 1, sex hormones, and binding proteins in relation to prostate cancer risk in the national cancer institute breast and prostate cancer cohort consortium

Konstantinos K. Tsilidis, Ruth C Travis, Paul N. Appleby, Naomi E. Allen, Sara Lindstrom, Fredrick R. Schumacher, David Cox, Ann W. Hsing, Jing Ma, Gianluca Severi, Demetrius Albanes, Jarmo Virtamo, Heiner Boeing, H Bas Bueno de Mesquita, Mattias Johansson, J. Ramón Quirós, Elio B Riboli, Afshan Siddiq, Anne Tjønneland, Dimitrios TrichopoulosRosario Tumino, J. Michael Gaziano, Edward Giovannucci, David J. Hunter, Peter Kraft, Meir Jonathan Stampfer, Graham G. Giles, Gerald L Andriole, Sonja I. Berndt, Stephen J Chanock, Richard B Hayes, Timothy J Key

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13 Citations (Scopus)


Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins. American Journal of Epidemiology.

Original languageEnglish
Pages (from-to)926-935
Number of pages10
JournalAmerican Journal of Epidemiology
Issue number9
Publication statusPublished - 1 May 2012
Externally publishedYes


  • gene-environment interaction
  • gonadal steroid hormones
  • insulin-like growth factor binding protein 3
  • insulin-like growth factor I
  • molecular epidemiology
  • prostatic neoplasms

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