SHIVANANDA B. NAYAK, VINUTHA R. BHAT, DINESH UPADHYAY
AND SARASWATI L. UDUPA*
Department of Biochemistry,
Kasturba Medical College,
Manipal - 576 119
(Received on September 10, 2001)

 

 

Key words : prostate, colon, cancer, copper trace element, ceruloplasmin, antioxidant

 

INTRODUCTION
METHODS
RESULTS AND DISCUSSION
REFERENCES

INTRODUCTION

The incidence of prostate and colon cancer is not only increasing in Western countries but also in the Indian population. They have been rated as the ninth and tenth most frequently occurring cancers in India (1). An association between oxidative stress and trace element levels in serum has been observed in breast cancer (2).  Although zinc and iron levels remained unaltered serum copper level was significantly increased.  Several other studies have also shown that plasma copper and ceruloplasmin, the glycoprotein which binds copper, are increased in various cancers (3-5).  Hence this study was taken up to assess copper and ceruloplasmin status in Indian patients with colon and prostate cancer.
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METHODS

The study was conducted on 20 patients each of colon and prostate cancer, using 20 normal healthy age and sex matched volunteers as controls. Random blood samples were collected from patients in vacutainer tubes and assayed for copper, ceruloplasmin, carcinoembryonic antigen (CEA) and prostate specific antigen (PSA).

Copper was assayed calorimetrically (6), while ceruloplasmin level was determined by the diamine oxidase method (7), based on the property of ceruloplasmin to catalyse the oxidation of' colorless para-phenylene diamine to a blue violet complex, which can be estimated spectrophotometrically PSA and CEA levels were assayed by autoanalyser based on the microparticle enzyme immunoassay (MEIA) supplied by Abbott Laboratories, USA (8) Appropriately diluted blood samples were incubated in reaction vessel well along with anti-PSA or anti-CEA coated microparticles.  PSA/CEA react with the anti-PSA/anti-CEA forming an antigen-antibody complex. The excess reaction mixture is washed off and the antigen-antibody complex is treated with 4methylumbelliferyl phosphate to give a fluorescent product which is measured by the analyzer's optical assembly.  Appropriate standard curves were made similarly. Statistical analysis was done using student's unpaired "t" test using SPSS/PC + package. Significance was determined by MannWhitney U test (P< .01, P<001 were taken as significant and highly significant respectively).
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RESULTS AND DISCUSSION

Table I depicts the serum levels of copper, ceruloplasmin, their ratio and CEA and PSA levels in control and cancer patients.  CEA was used as a marker for colon cancer and PSA for prostate cancer.  As expected, these markers were highly elevated in the cancer patients.  Copper and ceruloplasmin levels were also increased significantly in both colon and prostate cancer patients as compared to controls.

 

Table I click to view full image

Table I: Serum copper, Ceruloplasmin, CEA and PSA levels in colon and prostate cancer patients.

 

However, the increase was comparable within the two types of cancer.  Ratio of copper to ceruloplasmin was however not significantly different from controls.  CEA is a tumour associated antigen, originally thought to be specific for GIT cancer (9) but is also found to be now elevated in other malignancies (10) and non-malignant disorders (11).  However it continues to be used in follow up studies of patients with colon (12), breast (13) and lung cancers (14) and widely accepted as having prognostic significance.  PSA, a member of the human kallikrein gene family (15) is fairly specific for prostate cancer, since the major site of PSA production is the glandular epithelium of prostate.  Increased levels of serum PSA is thus associated with prostate pathology including malignancy (16).

Sufficient evidence has been accumulated in the recent years to implicate trace elements in the etiology of cancer (17).  Increased levels of copper were observed in lung (18), breast (2) and GIT (4) cancers.  Increased levels of copper and ceruloplasmin were reported in Indian women with breast cancer (5).  Cupric ions are reported to inhibit the production of singlet oxygen; this is of particular physiologic significance because of the latter's ability to cross the cell membrane and its high reactivity towards various biomolecules (19).

Ceruloplasmin is an acute phase protein which increases in several malignancies and is a storage protein for copper in the liver.  Increased levels of copper in serum of prostate and colon cancer patients may be due to the release of cytosolic and nuclear copper into the extracellular compartment.  Secondaries in liver might be contributory to the high levels of ceruloplasmin.

In the present study, there is a concomitant increase in copper and ceruloplasmin levels in serum of both prostate and colon cancer.  Vaidya and Kamalakar (5) also reported a similar finding in breast cancer patients.  They reported that these parameters came back to normal values after undergoing treatment.  Elevation of serum copper and ceruloplasmin levels have also been reported to be useful in diagnosis and prognosis of other malignancies (20).  Hence determination of serum copper and ceruloplasmin could be useful in diagnosis, prognosis and therapy evaluation of prostate and colon cancer patients along with PSA and CEA.
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REFERENCES

1.       Rao DN, Ganesh B. Estimate of cancer incidence in India in 1991.  Ind J Cancer 1998; 35: 10-18.

2.       Huang YL, Shen JV, Lin TH.  Association between oxidative stress and changes of trace elements in patients with breast cancer.  Clin Biochem 1999; 32(2): 131-136.

3.       Aryumanayagam M, Wong FW, Rogers M, Swaminathan R. Serum ceruloplasmin, plasma copper concentration and copper to ceruloplasmin ratio in cervical cancer.  Gynaec Obst Invest 1993; 35(3): 175-178.

4.       Narang AP, Verma A, Kumar GR, Sanyal B. Serum copper levels in GIT cancer.  J Trace Elem Elecetro Health Dis 1989; 3(3): 147-150.

5.       Vaidya SM, Kamalakar PL.  Copper and ceruloplasmin levels in serum of women with breast cancer.  Ind J Med Sci 1998; 52(5): 184-187.

6.       Zak B, Landers JW Copper in serum.  J Clin Pathol 1958;29:590-592.

7.       Ravan HA, Copper oxidase activity.  J Lab Clin Med 1961;58:161-163.

8.       Wayne PA.  National committee for clinical laboratory standards.  Approved guidelines NCCCLS procurement 1/LA 19-A: NCCLS: 1997.

9.       Skarin AT, Delwiche R. Careinoembryonic antigen : clinical correlation ith chemotherapy for metastatic GIT cancer.  Cancer 1974; 33: 1239-1244.

10.    Reynosa G, Chu TM.  Carcinoeiiibryonic antigen in patients with different cancers.  JAMA 1972; 220: 361-363.

11.    Alsabti EAK, Kaniel A. Carcinoembryonic antigen in patients with malignant and non-malignant disease.  Neoplasm 1979; 26: 603-606.

12.    Martin EW, Cooperman M. A retrospective and prospective study of cervical determinations in the early detection of recurrent colon cancer.  Am J Surg 1979; 137: 167-171.

13.    Steward AM, Nixen D. Carcinoembryonic antigen in breast cancer patients : Serum levels and disease progress.  Cancer 1974; 33: 1246-1247.

14.    Concannon JP, Dawbow MH.  Prognostic value of preoperative carcinoembryonic antigen plasma levels in patients with bronchogenic carcinoma. Cancer 1978; 42: 1477-1479.

15.    McCormack RT, Rittenhouse HG, Finlay JA.  Molecular forms of prostatic specific antigen and the human kallikrein gene family : a new era Urology 1995; 45: 729-744.

16.    Partin AW, Desterling JE.  The clinical usefulness of prostatic specific antigen Update 1994.  J Urol 1994;152:1358-1368.

17.    Jayadeep A, Raveendran PK, Kannan S, Nalini Kumari KR, Mathew B, Krishnan N, Menon VP.  Serum levels of copper, zinc, iron and ceruloplasmin in oral leukoplakia and squamous cell carcinoma. J Exp Clin Cancer Res 1997; 16(3): 295-300.

18.    Zhao X, Han C, Jing J. Relationship of serum trace elements to lung cancer and its clinical application. Chung Hua Liu Hsing Ping Hsuch Tsa Chih 1998; 19(5): 286-287.

19.    Joshi PC.  Copper (II) as an efficient scavenger of singlet molecular oxygen.  Ind Biochem Biophys 1998; 35(4): 208-215.

20.    Rajput BS, Gupta SN, Sur KN, Pandey RP, Singh S. Evaluation of serum copper levels in diagnosis and prognosis of various malignancies.  Ind J Surgery 1979; 41: 375-379.

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