M.

Prasad Naidu
MSc Medical Biochemistry, Ph.D,.
Dr.M.Krishnamma M.D(Biochemistry),D.G.O
Professor,
Dept of Biochemistry,
Narayana Medical College,Nellore.

Dr. V.Venu Gopal Reddy Professor (Community Medicine)
Mr. M.Prasad Naidu Ph.D.Research Scholar


INTRODUCTION
Prostate cancer is the most common malignancy among men
in developed and developing countries.

Incidence of prostate cancer is 5per 1,00,000 in southern
and eastern Asia.

Both genetic and environmental and nutritional factors
have been implicated in its etiology.

The mitogenic and growth stimulatory effects of Insulin
growth factor may be involved in prostate carcinogenesis.

Prostate specific antigen (PSA) & prostatic acid phosphatase
(ACP) are produced in the epithelial cells. Both cell types
express androgen receptors, & depend on androgen for
growth.(1)

The prostate protects itself against electrophilic attacks from
carcinogens by inducing a battery of enzymes, of which
glutathione S-transferase is the most prominent.
2

Normal concentration of prostate specific antigen is 1 to 5
g/L .
Total acid phosphatase 2.5 to 12 IU/L.
Tratrate (labile acid phosphatase <1IU/L.
Insulin suppresses the hepatic synthesis of SHBG, and
crosssectional studies reported an inverse correlation
between insulin and SHBG levels.

Decreased levels of SHBG result in increased levels of
the bioactive free fraction of testosterone entering the
prostate cells, which in turn may increase the risk of
prostate cancer.
Insulin resistance is associated with a higher risk of prostate
cancer among men and that insulin sensitivity is associated
with a reduced risk of prostate cancer among men.
3

Both genetic, environmental and nutritional factors have
been implicated in the etiology of prostate cancer.

Antioxidants like tocopherol (vit E),ascarbic acid vit c
and selenium may also reduce the risk.

Several molecular etiological pathways have been suggested
for prostate cancerandrogen transactivation pathways,
insulin like growth factor signaling pathways and chemical
carcinogenic pathways.
4

IGF-1 is known to increase the prostate cancer risk by
stimulating cellular proliferation of the prostate, and
IGFBP-3 is reported to prevent prostate cancer by
blunting the proliferative effect of IGF-1 on prostate
cells.

1,25(OH)2 vitamin D reduces prostate cancer cell growth
by multiple mechanisms, which include cell cycle arrest,
the induction of apoptosis, and regulation of growth
factor signaling.
A multidimensional model of cancer development
A simple model of prostate cancer development: possible interfaces of
etiological path ways.
Objectives:

To evaluate insulin resistance by HOMA- IR.

To estimate Prostatic specific antigen .

To estimate Antioxidant vitamins.
Materials and method:

In our study 30 prostate cancer patients aged 60-80years
were taken as cases.

30 normal age matched disease free person were taken as
controls in both groups, Insulin resistance and antioxidant
vitamin status was studied.
By using SPSS 17 version

1. To evaluate insulin resistance by homeostasis model
assessment of insulin resistance (HOMA-IR).
2. To estimate Prostatic specific antigen by immuno
enzymatic assay.
3. To estimate Antioxidant vitamins by high performance
liquid chromatography.
4. To estimate plasma Glucose by GOD POD.

5. HOMA IR= Plasma insulin mIU/LXPlasma glucose mg/dl
405

Results
In the present study, the value of HOMA-IR significantly
increased (p<0.05) in cases, compared to controls.

Serum vitamin E and vitamin C values for cases was
reduced (p<0.05) significantly than controls.

The results of the present study are consistent with the
findings showing an association between increased insulin
resistance, lowered antioxidant vitamin status and the
pathogenesis of prostate cancer.

Parameter Patients

Controls

P' value

t value

Mean S.D Mean S.D

PSA
21.489
7.1592

4.76
0.695106
Fasting insulin
19.266667
3.52266879

15.13333333
3.390995514
<0.0001 4.6301
Fasting glucose
63.76666667
3.901222915

62.93333333
2.448551061
0.3258 0.991
HOMA - IR
3.073333333
0.753361814

2.357333333
0.587583792
0.0001 4.1047
Vitamin E
0.339333333
0.124732357

0.585666667
0.117845116
<0.0001 7.8627
Vitamin C
30.44866667
10.72923455

51.69666667
14.49848466
<0.0001 6.4524
Increased insulin resistance in prostate cancer.
19.26
63.76
3.07
15.12
62.93
2.35
0
10
20
30
40
50
60
70
Fastin Insulin Fasting Glucose HOMA IR
Cases
Controls
Low level of antioxidant vitamin status and PSA pathogenesis
of prostate cancer
21.48
0.33
30.44
4.76
0.58
51.69
0
10
20
30
40
50
60
PSA Vitamin E Vitamin C
Cases
Controls
CONCLUSION
The development of prostate cancer is a multistep
process.

Hyperinsulinemia associated with insulin resistance
may play a role in the pathogenesis of prostate cancer
through its sympathoexcitatory effect, by altering sex
hormone metabolism, activating the IGF pathway,
through signal transduction mechanisms and via
dyslipidemia and inflammation.
Whether increased insulin resistance, either through
lifestyle changes or genetic susceptibility, increases
the risk of prostate cancer warrants further
investigation, especially in prospective studies.

Elevated fasting plasma insulin and other components
of the metabolic syndrome were associated with
greater prostate cancer mortality.

Prostate cancer cells generate high levels a ROS and
the generation of ROS increases with aggre ssiveness
of the cells.


Recent work has shown that vitamin E suppresses the
expression of androgen receptor in prostate cancer
cells and helps to establish new therapeutic concepts
for the prevention and treatment of prostate cancer.

Vitamin C has role in regeneration of tocopherol from
phenoxy free radical derivative.

A decreased prostate cancer risk was observed with
increasing intakes of vitamin C-rich vegetables.

REFERENCE
1. Harrison principles of internal medicine 16
th
edition : volume
number 1; hyperplastic and malignant diseases of the prostate
; chapter 81; pages 543 -553
2.Campbells Urology, 7
th
Edition ,Edited by Walsh, Retik
,Vaughan , Wein: Volume number 2 :Chapter 45: The
molecular biology and endocrinology of the prostate and
seminal vesicles. Pages 1381- 1428.
3. Hsing AW , Devesa SS. Trends amd pattern of prostate cancer
; what do they suggest ? Epidemiology review 23 : 30 35 ,
2001 : Hormones , genes , and cancer Henderson , Ponder ,
Ross : Oxford university press 2003 : Prostate Cancer:
Epidemiology & Molecular biology chapter 15 pages 273 -
287 .

4. Insulin Resistance and Prostate Cancer Risk :Ann W. Hsing,
Yu-Tang Gao, Streamson Chua, Jr., Jie Deng, Frank Z.
Stanczyk: Journal of the National Cancer Institute, Vol. 95, No.
1, January 1, 2003