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.

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.

• Authors: 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 Trichopoulos, Rosario 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
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 175 Issue 9 Pg. 926-35 (May 01 2012) ISSN: 1476-6256 [Electronic] United States
• PMID: 22459122 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Gonadal Steroid Hormones
• IGFBP3 protein, human
• Insulin-Like Growth Factor Binding Protein 3
• Sex Hormone-Binding Globulin
• Insulin-Like Growth Factor I

Topics

• Aged
• Case-Control Studies
• Genome-Wide Association Study
• Gonadal Steroid Hormones (blood)
• Humans
• Insulin-Like Growth Factor Binding Protein 3 (blood)
• Insulin-Like Growth Factor I (metabolism)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (blood, genetics)
• Sex Hormone-Binding Globulin (metabolism)