黑人男性中与维生素D相关的基因变异与前列腺癌风险

Vitamin D-related genetic variants and prostate cancer risk in Black men.

作者信息

Layne Tracy M, Rothstein Joseph H, Song Xiaoyu, Andersen Shaneda Warren, Benn Emma K T, Sieh Weiva, Klein Robert J

机构信息

Center for Scientific Diversity and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.

出版信息

Cancer Epidemiol. 2025 Apr;95:102742. doi: 10.1016/j.canep.2025.102742. Epub 2025 Jan 16.

DOI:10.1016/j.canep.2025.102742

PMID:39823710

Abstract

BACKGROUND

The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

METHODS

We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men for comparison. A statistical significance threshold of 0.000685 was used to account for the 73 variants tested.

RESULTS

None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Suggestive associations (P < 0.05) for four variants were found in Black men, including two in RXRA (rs41400444 OR=1.09, 95 % CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055).

CONCLUSION

We observed suggestive associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

摘要

背景

维生素D与前列腺癌之间的关系主要在白人男性中得到了描述。然而，黑人男性的前列腺癌发病率和死亡率更高，循环维生素D水平长期较低，并且在维生素D相关基因中存在特定祖先的基因变异。在此，我们研究了黑人男性中维生素D途径的关键基因与前列腺癌风险的关系。

方法

我们评估了基因（即GC、CYP27A1、CYP27B1、CYP24A1、VDR和RXRA）中的总共73个候选变异，包括先前与白人男性前列腺癌和循环25(OHD)相关的功能变异。使用全基因组关联研究数据，对黑人男性中约10,000例前列腺癌病例和10,000例对照，以及白人男性中超过85,000例病例和91,000例对照进行比较，以研究与前列腺癌风险的关联。采用0.000685的统计显著性阈值来考虑所测试的73个变异。

结果

在进行多重比较调整后，黑人男性中所检测的变异均未与前列腺癌风险显著相关。在黑人男性中发现了四个变异的提示性关联（P<0.05），包括RXRA中的两个（rs41400444，OR=1.09，95%CI：1.01-1.17，P=0.024；rs10881574，OR=0.93，0.87-1.00，P=0.046）和VDR中的两个（rs2853563，OR=1.07，1.01-1.13，P=0.017；rs1156882，OR=1.06，1.00-1.12，P=0.045）。VDR中的两个变异在白人男性中也与风险呈正相关（rs11568820，OR=1.04，1.02-1.06，P=0.00024；rs4516035，OR=1.03，1.01-1.04，P=0.00055）。