Official organ of the Association of Physiologist and Pharmacologists of India


Original Article
Volume 47 - No.1:January 2003 (index)
Indian J Physiol Pharmacol  2003;

Copper and Ceruloplasmin Status in Serum of Prostate and Colon Cancer Patients

Department of Biochemistry,
Kasturba Medical College,
Manipal - 576 119

(Received on September 10, 2001)


Abstract : Serum copper and ceruloplasmin levels were estimated in 20 patients each of prostate and colon cancer.  Although copper to ceruloplasmin ratio was not significantly altered, copper and ceruloplasmin levels were increased significantly in the cancer patients as compared to' controls.  Trace elements and free radicals have been implicated in the etiology of cancer.  Hence determination of specific antioxidants (like ceruloplasmin) and trace elements (like copper) may be of value in the early diagnosis of prostate and colon cancer.


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




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.



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).


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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