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