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

被引：0
作者：
Layne, Tracy M. [1 ,2 ]
Rothstein, Joseph H. [3 ,4 ]
Song, Xiaoyu [5 ]
Andersen, Shaneda Warren [6 ]
Benn, Emma K. T. [1 ,2 ]
Sieh, Weiva [3 ,4 ]
Klein, Robert J. [3 ]
机构：
[1] Icahn Sch Med Mt Sinai, Ctr Sci Divers, New York, NY USA
[2] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY USA
[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA
[5] Ctr Quantitat Med, Duke NUS Med Sch, Singapore, Singapore
[6] Univ Wisconsin Madison, Dept Populat Hlth Sci, Madison, WI USA
来源：
CANCER EPIDEMIOLOGY | 2025年 / 95卷
基金：
美国国家卫生研究院; 瑞典研究理事会;
关键词：
Cancer disparities; Vitamin D; Cancer genomics; Cancer risk; Prostate cancer; D-BINDING PROTEIN; RECENT POSITIVE SELECTION; GENOME-WIDE ASSOCIATION; D PATHWAY; MENDELIAN RANDOMIZATION; 25-HYDROXYVITAMIN D; CALCIUM INTAKE; POLYMORPHISMS; BREAST; 1,25-DIHYDROXYVITAMIN-D;
D O I：
10.1016/j.canep.2025.102742
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：6
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