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 Riboli, Afshan Siddiq, Anne Tjønneland, Dimitrios TrichopoulosRosario Tumino, J. Michael Gaziano, Edward Giovannucci, David J. Hunter, Peter Kraft, Meir J. Stampfer, Graham G. Giles, Gerald L. Andriole, Sonja I. Berndt, Stephen J. Chanock, Richard B. Hayes, Timothy J. Key

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)926-935
Number of pages10
JournalAmerican journal of epidemiology
Volume175
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Epidemiology

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    Tsilidis, K. K., Travis, R. C., Appleby, P. N., Allen, N. E., Lindstrom, S., Schumacher, F. R., Cox, D., Hsing, A. W., Ma, J., Severi, G., Albanes, D., Virtamo, J., Boeing, H., Bueno-De-Mesquita, H. B., Johansson, M., Quirós, J. R., Riboli, E., Siddiq, A., Tjønneland, A., ... Key, T. J. (2012). 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. American journal of epidemiology, 175(9), 926-935. https://doi.org/10.1093/aje/kwr423