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.
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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美国国家癌症研究所 BPC3 中全基因组显着遗传变异与 25-羟基维生素 D 循环浓度与前列腺癌风险之间的相互作用。
DOI：
10.1093/aje/kww143
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发表时间：
2017
影响因子：
5
通讯作者：
Tri
中科院分区：
文献类型：
--
作者：
Dimitrakopoulou,VasilikiI;Travis,RuthC;Shui,IreneM;Mondul,Alison;Albanes,Demetrius;Virtamo,Jarmo;Agudo,Antonio;Boeing,Heiner;Bueno-de-Mesquita,HBas;Gunter,MarcJ;Johansson,Mattias;Khaw,Kay-Tee;Overvad,Kim;Palli,Domenico;Tri
全基因组关联研究（GWAS）已经确定了100多个与前列腺癌相关的单核苷酸多态性（SNP）。然而，关于某些协会的机械基础的信息有限。最近的研究已经针对维生素D浓度和前列腺癌的潜在关联，但对上述遗传关联是否被维生素D修饰知之甚少。我们调查了46个GWAS鉴定的SNP、25-羟基维生素D（25（OH）D）的循环浓度和前列腺癌（3，811例，其中511例死于该疾病，与2，980例对照相比-来自5个队列研究，这些研究招募了20世纪80年代开始的几个时期的参与者）的关联。我们使用逻辑回归模型与来自美国国家癌症研究所乳腺癌和前列腺癌队列联盟（BPC 3）的数据，以评估乘法和加法尺度上的相互作用。在允许多次测试后，没有一个SNP与25（OH）D浓度显著相关，SNP与前列腺癌的相关性在这些浓度下没有差异。在乘法和加法量表上，观察到8 q24区域的2个SNP（rs620861和rs 16902094）、25（OH）D浓度和致死性前列腺癌的统计学显著相互作用（P≤ 0.001）。我们没有发现强有力的证据表明GWAS鉴定的SNP与前列腺癌之间的关联被25（OH）D的循环浓度改变。rs620861和rs 16902094之间有趣的相互作用，25（OH）D浓度和致命的前列腺癌值得复制。
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.
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