1. Vitamin D and Prostate Cancer
Ammar Zaki Mahmood Al-Janabi
Master - Medical Biochemistry
ammar.zaki89@yahoo.com
Near East University
Faculty of Medicine
Nicosia, Cyprus
21/ Jun/ 2016
11: 30 am
Tuesday
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2. Outline
• Introduction
• Prostate Gland
• Prostate Cancer
• Vitamin D
• Introduction to Vitamin D
• Vitamin D Analogs
• Metabolic Activation of Vitamin D
• Mechanism of Anticancer Genes Expression
• Functions of Vitamin D
• Review of the Epidemiological Evidence
• Summary
• Referential Articles
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3. Prostate Gland
• Location
• Below the Bladder.
• In front of the Rectum.
• Surrounding the upper
part of the urethra.
• Function
• Producing a secretion forms a part of the semenal
fluid that mixes with it right before ejaculation.
• This secretion is essential for the mobility and the
survival of the sperm.
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4. Prostate Cancer
Prostate Cancer (PCa) is the second-most frequently
diagnosed cancer in males around the world.
It’s also one of the leading causes of cancer death among
men of all races.
Few risk factors have been established for PCa other than
older age, a positive family history, and race.
Some previous epidemiological studies suggested that low
serum levels of vitamin D receptor (VDR) might be a risk
factor for PCa.
4Referential Article 1
5. Prostate Cancer
Such low levels could be recognized by 1α,25
dihydroxyvitamin D3 (active form of vitamin D) and it’s
analogs.
Through the interaction of these substances the tumor cell
cycle could be fixed in the G1 Phase, leading to stagnation
of the tumor cells.
5Referential Article 1
7. Introduction to Vitamin D
Prostate cell division is influenced by two steroid hormones:
testosterone and vitamin D.
The action of these hormones is mediated by their respective
receptors: androgen receptor (AR) and Vitamin D Receptor
(VDR).
Prostate epithelial cells express multiple members of nuclear
receptor superfamily that regulate proliferation and
differentiation of cells in the prostate gland.
7Referential Article 3
8. Introduction to Vitamin D
The action of these hormones is disturbed in PCa,
presenting molecular alterations and mutations related to the
diagnosis of the disease and response to therapy.
VDR is a member of the superfamily of nuclear hormone
receptors that regulate gene transcription.
The idea that the VDR gene may influence the occurrence of
PCa and other diseases is mainly based on the notion that
vitamin D is implicated in a wide variety of biological
processes.
8Referential Article 3
9. Vitamin D Analogs
Vitamin D2 and D3 is not
biologically active forms of
Vitamin D and they can’t
achieve full hormonal
function until they get
activated by the body’s
metabolism.
The total circulating
concentration of 25(OH)D is
the biomarker that is most
frequently used in
epidemiological
investigations.
9Referential Article 4
10. Vitamin D Rich Natural Food
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Egg
Cod Liver Oil Oysters
Fish
Mushrooms
Diary
ProductsFortified
cereals
11. Metabolic Activation of Vitamin D
11Referential Article 4
Circulation
Provitamin D3
(7-dehydrocholestrol)
Previtamin D3
Endogenous
Skin
UV
Synthesis
12. Metabolic Activation of Vitamin D
12Referential Article 4
Circulation
Previtamin D3
Thermal
Vitamin D3
Isomerization
13. Metabolic Activation of Vitamin D
13Referential Article 4
25-
Vitamin D3
25(OH) D3
hydroxylase
14. Metabolic Activation of Vitamin D
14Referential Article 4
25(OH) D3 1α,25(OH)2 D3
hydroxylase1α-
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16. Metabolic Activation of Vitamin D
16Referential Article 4
The final product of this process (1α,25 (OH)2 D3) is the most
active form of vitamin D and the less abundant compared
with the rest of vitamin D analogs.
Because, as long as it is the most active, so once it’s produced
it’s consumed in many biological processes including
modulation of the immune response and inhibition of cancer
cell growth, angiogenesis and metastasis etc.
17. Metabolic Activation of Vitamin D
17Referential Article 4
Any break in this
activation process such as
inadequate oral intake,
inadequate sun light, liver
disease or kidney disease
can lead to vitamin D
deficiency.
Even increased skin
pigmentation is associated,
and as such, African-
Americans have
significantly lower 25
(OH) D3 levels than any
other group in the U.S.
20. Review of the Epidemiological Evidence
Vitamin D has been the subject of intense scrutiny in
relation to various cancer endpoints with particular focus on
the incidence and mortality of colorectal, breast, and
prostate cancers.
Together, these three malignancies account for
approximately 35% of cancer cases and 20% of cancer
deaths in the United States.
Regarding prostate cancer, approximately 30 studies of the
association between 25 (OH) D3 and prostate cancer
incidence have been conducted.
20Referential Article 6
21. Review of the Epidemiological Evidence
Of these, only two have reported a clear and statistically
significant inverse relationship for overall risk of prostate
cancer.
while an additional five studies demonstrated an increased
risk for prostate cancer associated with higher
concentrations of 25 (OH) D3.
The remainder of the published reports are null for the
endpoint of overall prostate cancer incidence.
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22. Review of the Epidemiological Evidence
however, a meta-analysis published in 2014 of 21 studies
reported a statistically significant finding that higher 25
(OH) D3 concentrations were related to a higher risk for
developing prostate cancer.
Taken together, epidemiological association studies have
provided no convincing evidence that higher concentrations
of 25 (OH) D3 might reduce the risk of developing prostate
cancer.
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23. Review of the Epidemiological Evidence
Regarding mortality, studies conducted to date of 25 (OH)
D3 and prostate cancer mortality have been equivocal, with
some studies showing a significant inverse association and
others being null.
Therefore, there is no convincing evidence that vitamin D
will prevent prostate cancer, some evidence that it may
prevent progression of early-stage disease, and inconsistent
findings for mortality.
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24. Review of the Epidemiological Evidence
Overall, association studies of circulating concentrations of
25 (OH) D3 and colorectal, breast, and prostate cancer
incidence, progression, or mortality have yielded a wide
range of results of varying consistency.
In following Figure, the evidence is strongest for an
association between 25 (OH) D3 and colorectal cancer
incidence and mortality, and breast cancer progression
and/or mortality.
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25. Summary
Summary of findings from observational epidemiological studies of
25 (OH) D3 in the carcinogenesis pathway of colorectal, breast, and
prostate cancers. Solid-colored bars represent consistent evidence for
protection against cancer, white bars represent no evidence, and
hashed bars represent inconsistent evidence for the association
between 25 (OH) D3 and the indicated endpoints of pre-cancerous
lesions, cancer incidence, progression and mortality.
25Referential Article 6
26. Referential Articles
1. Onco Targets and Therapy, 1/March/2016
Polymorphisms of vitamin D receptor gene TaqI susceptibility
of prostate cancer: a meta-analysis.
http://www.ncbi.nlm.nih.gov/pubmed/27042096
2. British Institute of Radiology, 16/May/2016
Staging of prostatic carcinoma at 1.5 T MRI: correlation of a
simplified MRI exam with whole mount radical prostatectomy
specimens.
http://www.ncbi.nlm.nih.gov/pubmed/27181821
3. Springer Plus, 24/March/2016
Association of vitamin D receptor variants with clinical parameters
in prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/?term=Association+of%C2%A0vitamin+D%
C2%A0receptor+variants+with+clinical+parameters+in%C2%A0prostate+cancer.
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27. Referential Articles
4. Frontiers in Immunology, 22/February /2016
Vitamin D and Immune Response: Implications for Prostate Cancer in
African Americans
http://www.ncbi.nlm.nih.gov/pubmed/?term=Vitamin+D+and+Immune+Response%3A
+Implications+for+Prostate+Cancer+in+African+Americans
5. American Journal of Hematology / Oncology, October / 2015
Anticancer Effects of Vitamin D
http://www.gotoper.com/publications/ajho/2015/2015Oct/Anticancer-Effects-of-
Vitamin-D
6. Journal of Cancer, 5/Jan/ 2016
Vitamin D and Colorectal, Breast, and Prostate Cancers: A Review of
the Epidemiological Evidence
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747876/
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