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.
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Authors
Dimitrakopoulou, Vasiliki ITravis, Ruth C
Shui, Irene M
Mondul, Alison
Albanes, Demetrius
Virtamo, Jarmo
Agudo, Antonio
Boeing, Heiner
Bueno-de-Mesquita, H Bas
Gunter, Marc J
Johansson, Mattias
Khaw, Kay-Tee
Overvad, Kim
Palli, Domenico
Trichopoulou, Antonia
Giovannucci, Edward
Hunter, David J
Lindström, Sara
Willett, Walter
Gaziano, J Michael
Stampfer, Meir
Berg, Christine
Berndt, Sonja I
Black, Amanda
Hoover, Robert N
Kraft, Peter
Key, Timothy J
Tsilidis, Konstantinos K
Type
ArticleLanguage
en
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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.Published in
Am J Epidemiol 2017; 185(6):452-64Publiekssamenvatting
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.PMID
28399564ae974a485f413a2113503eed53cd6c53
10.1093/aje/kww143
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