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Intratumoral vitamin D signaling and lethal prostate cancer.
Vaselkiv, Jane B; Shui, Irene M; Grob, Sydney T; Ericsson, Caroline I; Giovannucci, Isabel; Peng, Cheng; Finn, Stephen P; Mucci, Lorelei A; Penney, Kathryn L; Stopsack, Konrad H.
Afiliação
  • Vaselkiv JB; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Shui IM; Merck & Co., Inc., Kenilworth, NJ, United States.
  • Grob ST; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Ericsson CI; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Giovannucci I; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Peng C; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Finn SP; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
  • Mucci LA; Department of Pathology, Trinity College Dublin, Dublin, Ireland.
  • Penney KL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
  • Stopsack KH; Discovery Science, American Cancer Society, Atlanta, GA, United States.
Carcinogenesis ; 45(10): 735-744, 2024 Oct 10.
Article em En | MEDLINE | ID: mdl-39120256
ABSTRACT
High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1, CYP2R1, RXRA, RXRB, and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile 0.46, 95% confidence interval 0.21-0.99) in a dose-response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Aged / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Aged / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article