Interactions Between Genome-Wide Significant Genetic Variants and Circulating Concentrations of 25-Hydroxyvitamin D in Relation to Prostate Cancer Risk in the National Cancer Institute BPC3.

Abstract

Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls-from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP-prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (P ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.

• Authors: Vasiliki I Dimitrakopoulou, Ruth C Travis, Irene M Shui, Alison Mondul, Demetrius Albanes, Jarmo Virtamo, Antonio Agudo, Heiner Boeing, H Bas Bueno-de-Mesquita, Marc J Gunter, Mattias Johansson, Kay-Tee Khaw, Kim Overvad, Domenico Palli, Antonia Trichopoulou, Edward Giovannucci, David J Hunter, Sara Lindström, Walter Willett, J Michael Gaziano, Meir Stampfer, Christine Berg, Sonja I Berndt, Amanda Black, Robert N Hoover, Peter Kraft, Timothy J Key, Konstantinos K Tsilidis
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 185 Issue 6 Pg. 452-464 (03 15 2017) ISSN: 1476-6256 [Electronic] United States
• PMID: 28399564 (Publication Type: Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Vitamin D
• 25-hydroxyvitamin D

Topics

• Aged
• Case-Control Studies
• Gene-Environment Interaction
• Genome-Wide Association Study
• Genotype
• Humans
• Logistic Models
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (blood, genetics, mortality, prevention & control)
• Protective Factors
• Risk Assessment
• Vitamin D (analogs & derivatives, blood, genetics)