PROSTATE CANCER

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STUDY OF INSULIN RESISTANCE AND ANTIOXIDANT
VITAMIN STATUS IN PROSTATE CANCER

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

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• Dr.M.Krishnamma M.D(Biochemistry),D.G.OProfessor,
  
• Dept of Biochemistry,
• Narayana Medical College,Nellore.
• Dr. V.Venu Gopal Reddy Professor (Community
  Medicine)
• Mr. M.Prasad Naidu Ph.D.Research Scholar

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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.

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• 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 µg/L .
• Total acid phosphatase 2.5 to 12 IU/L.
• Tratrate (labile acid phosphatase lt1IU/L.

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• 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.

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• 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 a 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

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• 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.

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A multidimensional model of cancer development
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A simple model of prostate cancer development
possible interfaces of etiological path ways.
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• Objectives
• To evaluate insulin resistance by HOMA- IR.
• To estimate Prostatic specific antigen .
• To estimate Antioxidant vitamins.

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• 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

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• To evaluate insulin resistance by homeostasis
  model assessment of insulin resistance (HOMA-IR).
  
• To estimate Prostatic specific antigen by immuno
  enzymatic assay.
• To estimate Antioxidant vitamins by high
  performance liquid chromatography.
• To estimate plasma Glucose by GOD POD.
• HOMA IR Plasma insulin mIU/LXPlasma glucose
  mg/dl
• 
  405

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Results

• In the present study, the value of HOMA-IR
  significantly increased (plt0.05) in cases,
  compared to controls.
• Serum vitamin E and vitamin C values for cases
  was reduced (plt0.05) significantly than
  controls.

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• 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.

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Parameter Patients Patients Controls Controls P' value t value
Parameter Mean S.D Mean S.D P' value t value
PSA 21.489 7.1592 4.76 0.695106
Fasting insulin 19.266667 3.52266879 15.13333333 3.390995514 lt0.0001 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 lt0.0001 7.8627
Vitamin C 30.44866667 10.72923455 51.69666667 14.49848466 lt0.0001 6.4524
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Increased insulin resistance in prostate cancer.
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Low level of antioxidant vitamin status and PSA
pathogenesis of prostate cancer
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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.

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• 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.

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• 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.

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REFERENCE

• 1. Harrison principles of internal medicine 16th
  edition volume number 1 hyperplastic and
  malignant diseases of the prostate chapter 81
  pages 543 -553
• 2.Campbells Urology, 7th 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 .

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• 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

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Thank you