TY - JOUR
T1 - Association among plasma 1,25(OH)2D, ratio of 1,25(OH)2D to 25(OH)D, and prostate cancer aggressiveness
AU - Ramakrishnan, Swathi
AU - Steck, Susan E.
AU - Arab, Lenore
AU - Zhang, Hongmei
AU - Bensen, Jeannette T.
AU - Fontham, Elizabeth T.H.
AU - Johnson, Candace S.
AU - Mohler, James L.
AU - Smith, Gary J.
AU - Su, L. Joseph
AU - Woloszynska, Anna
N1 - Funding Information:
The authors would like to acknowledge the University of North Carolina BioSpecimen Facility and the Louisiana State University Health Sciences Center Pathology Lab for blood processing, storage, and sample disbursements (https://genome.unc.edu/bsp). The authors thank the staff, advisory committees and research subjects participating in PCaP for their important contributions. PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17‐03‐2–0052, and the current ancillary study is supported by DAMD 11‐1‐0568. AW is supported by DoD grant W81WH11‐1‐0308PCa. CSJ is supported by NIH grants CA067267, CA137650, and CA016056.
Publisher Copyright:
© 2019 The Authors. The Prostate Published by Wiley Periodicals, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men. Objective: To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)2D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer. Design: Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)2D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease. Results: Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)2D had lower odds of high aggressive prostate cancer (AA [ORT2vsT1: 0.66, 95%CI: 0.39-1.12; ORT3vsT1: 0.83, 95%CI: 0.49-1.41] and EA [ORT2vsT1: 0.68, 95%CI: 0.41-1.11; ORT3vsT1: 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)2D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (ORQ4vsQ1: 0.45, CI: 0.24-0.82) than in EA (ORQ4vsQ1: 0.64, CI: 0.35-1.17) research subjects. Conclusions: The 1,25(OH)2D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.
AB - Background: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men. Objective: To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)2D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer. Design: Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)2D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease. Results: Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)2D had lower odds of high aggressive prostate cancer (AA [ORT2vsT1: 0.66, 95%CI: 0.39-1.12; ORT3vsT1: 0.83, 95%CI: 0.49-1.41] and EA [ORT2vsT1: 0.68, 95%CI: 0.41-1.11; ORT3vsT1: 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)2D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (ORQ4vsQ1: 0.45, CI: 0.24-0.82) than in EA (ORQ4vsQ1: 0.64, CI: 0.35-1.17) research subjects. Conclusions: The 1,25(OH)2D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.
KW - prostate cancer
KW - racial disparities
KW - vitamin D
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U2 - 10.1002/pros.23824
DO - 10.1002/pros.23824
M3 - Article
C2 - 31077420
AN - SCOPUS:85066407451
SN - 0270-4137
VL - 79
SP - 1117
EP - 1124
JO - Prostate
JF - Prostate
IS - 10
ER -