vitamin d and prostate cancer

Vitamin D and Prostate Cancer

Ammar Zaki Mahmood Al-JanabiMaster - Medical Biochemistry [email protected] East UniversityFaculty of MedicineNicosia, Cyprus21/ Jun/ 201611: 30 amTuesday

1

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

2

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.

3

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

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.


Stages of Prostate Cancer


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.


Introduction to Vitamin DThe 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.


Vitamin D AnalogsVitamin 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.


Vitamin D Rich Natural Food

10

Egg

Cod Liver Oil Oysters

Fish

Mushrooms

Diary Products Fortified

cereals

D

Metabolic Activation of Vitamin D


Circulation

Provitamin D3

(7-dehydrocholestrol)Previtamin D3

Endogenous

Skin UV

Synthesis



CirculationPrevitamin D3

Thermal

Vitamin D3

Isomerization



25-

Vitamin D325(OH) D3

hydroxylase



25(OH) D3 1α,25(OH)2 D3

hydroxylase1α-



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.



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.

Mechanism of Anticancer Genes Expression


Functions of Vitamin D


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.



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.



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.



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.



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.


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.


Referential Articles

1. Onco Targets and Therapy, 1/March/2016Polymorphisms 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/2016Staging 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/2016Association 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.

26

Referential Articles

4. Frontiers in Immunology, 22/February /2016 Vitamin D and Immune Response: Implications for Prostate Cancer in African Americanshttp://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 / 2015Anticancer Effects of Vitamin Dhttp://www.gotoper.com/publications/ajho/2015/2015Oct/Anticancer-Effects-of-Vitamin-D

6. Journal of Cancer, 5/Jan/ 2016Vitamin D and Colorectal, Breast, and Prostate Cancers: A Review of the Epidemiological Evidencehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747876/

27

28

Any Questions?

Thank God For GuidanceThank My Doctors For Supervision

andThank You For Listening

vitamin d and prostate cancer

Documents