Vitamin D and prostate cancer prognosis: a Mendelian randomization study

Trummer, Olivia; Langsenlehner, Uwe; Krenn-Pilko, S.; Pieber, Thomas R.; Obermayer–Pietsch, Barbara; Gerger, Armin; Renner, Wilfried; Langsenlehner, Tanja

doi:10.1007/s00345-015-1646-9

Cited by 19 publications

(10 citation statements)

References 26 publications

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“…A detailed description has been published previously [13–15]. Briefly, PROCAGENE is a prospective study aimed at investigating genetic risk factors, functional relationships between genetic variations and clinical phenotypes, the genetically modified response to radiotherapy (radiogenomics), and the prognostic importance of genetic markers such as genetic variants in regulators of DNA repair, cell cycle, and apoptosis, including BCL2 -938C>A genotypes [16–21].…”

Section: Methodsmentioning

confidence: 99%

BCL2 genotypes and prostate cancer survival

Renner

Langsenlehner²,

Krenn-Pilko

et al. 2017

Strahlenther Onkol

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PurposeThe antiapoptotic B‑cell lymphoma 2 (BCL2) gene is a key player in cancer development and progression. A functional single-nucleotide polymorphism (c.-938C>A, rs2279115) in the inhibitory P2 BCL2 gene promoter has been associated with clinical outcomes in various types of cancer. Aim of the present study was to analyze the role of BCL2-938C>A genotypes in prostate cancer mortality.MethodsThe association between BCL2-938C>A (rs2279115) genotypes and prostate cancer outcome was studied within the prospective PROCAGENE study comprising 702 prostate cancer patients.ResultsDuring a median follow-up time of 92 months, 120 (17.1%) patients died. A univariate Cox regression model showed a significant association of the CC genotype with reduced cancer-specific survival (CSS; hazard ratio, HR, 2.13, 95% confidence interval, CI, 1.10–4.12; p = 0.024) and overall survival (OS; HR 2.34, 95% CI 1.58–3.47; p < 0.001). In a multivariate Cox regression model including age at diagnosis, risk group, and androgen deprivation therapy, the CC genotype remained a significant predictor of poor CSS (HR 2.05, 95% CI 1.05–3.99; p = 0.034) and OS (HR 2.25, 95% CI 1.51–3.36; p < 0.001).ConclusionThis study provides evidence that the homozygous BCL2-938 CC genotype is associated with OS and C in prostate cancer patients.

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Section: Methodsmentioning

confidence: 99%

BCL2 genotypes and prostate cancer survival

Renner

Langsenlehner²,

Krenn-Pilko

et al. 2017

Strahlenther Onkol

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“…The Austrian Prostate Cancer Genetics (PROCAGENE) study included 702 prostate cancer patients who were recruited between January 2004 and January 2007. A detailed description has been published previously 24 – 26 . Briefly, PROCAGENE is a prospective study aimed to investigate genetic risk factors, functional relationships between genetic variations and clinical phenotypes, genetically modified response to radiotherapy (radiogenomics), and the prognostic importance of genetic markers 27 – 30 .…”

Section: Methodsmentioning

confidence: 99%

“…Follow-up examinations were performed in regular intervals at the Department of Therapeutic Radiology and Oncology 26 . The primary study endpoint was overall mortality.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin polymorphism and prostate cancer mortality

Kaiser

Thurner

Mangge

et al. 2020

Sci Rep

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Prostate cancer is a common malignancy in men worldwide and it is known that oxidative stress is a risk factor for cancer development. A common functional haptoglobin (Hp) polymorphism, originating from a duplication of a gene segment spanning over two exons, results in three distinct phenotypes with different anti-oxidative capacities: Hp1-1, Hp1-2, and Hp2-2. The aim of the study was to investigate the relationship between this Hp polymorphism and prostate cancer mortality. The study was performed on 690 patients with histologically confirmed prostate cancer, recruited between January 2004 and January 2007. Hp genotypes were determined by a TaqMan fluorogenic 5′-exonuclease assay. Hp1-1 was present in 76 (11%), Hp1-2 in 314 (45.5%), and Hp2-2 in 300 (43.5%) patients. During a median follow-up of 149 months, 251 (35.3%) patients died. Hp genotypes were not significantly associated with higher overall mortality (HR 1.10; 95% CI 0.91–1.33; p = 0.34). This remained similar in a multivariate analysis including age at diagnosis, androgen deprivation therapy, and risk group based on PSA level, GS, and T stage (HR 1.11; 95% CI 0.91–1.34; p = 0.30). We conclude that the common Hp polymorphism does not seem to be associated with overall mortality in prostate cancer patients.

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“…Discrepancies in the investigated cohorts' characteristics, such as age, BMI, baseline vitamin D status, the dosage of serum vitamin D levels in pre and post diagnosis phase or in different stages of the disease, as well as the presence or absence of adjustment for potential confounding factors, might contribute to inconsistency among studies and to a challenging interpretation of data. However, recent findings demonstrated that isoforms of VDR [98], vitamin D-metabolizing genes [99,100] and DBP [6,101] may be associated with prostate cancer risks or clinical outcomes. The inconsistent findings on the role of vitamin D in prostate cancer can be explained by the interference of insulin like growth factor (IGF) axis components, notoriously involved in prostate cancer etiology and progression [102], which may compromise the antiproliferative vitamin D action.…”

Section: Vitamin D and Cancer: Epidemiological Evidencementioning

confidence: 99%

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

et al. 2020

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Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

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Vitamin D and prostate cancer prognosis: a Mendelian randomization study

Abstract: A causal role of vitamin D status, as reflected by GC rs2282679 genotype, in disease progression and mortality in prostate cancer patients is unlikely.

Cited by 19 publications

References 26 publications

BCL2 genotypes and prostate cancer survival

BCL2 genotypes and prostate cancer survival

Haptoglobin polymorphism and prostate cancer mortality

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

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