SERUM FERRITIN LEVELS AND TRANSFERRIN
SATURATION IN MEN WITH PROSTATE CANCER
Solo R. Kuvibidila, PhD; Tony Gauthier, MD; and Walter Rayford MD, PhD, FACS
New Orleans, Louisiana
Elevated body iron stores (serum ferritin >300 pg/L, transferrin saturation TS >50%) are associ-
ated with increased risk of liver and lung cancers. To determine whether such association also
exists for prostate cancer (PC), we measured serum ferritin, serum iron, total iron-binding capacity
(TIBC), and TS in serum samples from 34 men with newly diagnosed, untreated PC and 84 healthy
men, ranging in age from 49-78 years. In contrast with other malignancies, men with PC had signif-
icantly lower mean concentrations of serum ferritin (156 pg/L) and TS (24.35%) than those without
PC (ferritin, 245 pg/L; TS, 31.98%) (p<0.05). The 95% confidence intervals for ferritin were
109-203 pg/L and 205-286 pg/L, and those forTS were 20.29-28.4% and 28.35-35.61% for men
with and without PC, respectively. Significant differences were observed between both groups in
the distribution of serum ferritin (<100, 101-300, >300 pg/L) and TS (<16, 16-50, >50%) (p<0.05).
A lower percentage of cases than of controls had serum ferritin (17.6% versus 29.8%) and TS
(5.9% versus 14.7%) above normal. These differences persisted when the analysis was limited to
African-American men (31 cases and 52 controls). Data suggest that elevated body iron stores are
less common in men with PC compared to those without PC. (JNatlMedAssoc. 2004;96:641-649.)
Key words: serum ferritin * iron overload *
iron deficiency * transferrin saturation-
Cancer ofthe prostate is the most common non-
skin cancer in American men and the fourth most
common cancer in men throughout the world.",2 In
2003, 220,900 new cases are expected to be diag-
nosed in the United States, and 28,900 deaths are
anticipated.3 In addition to a family history of
prostate cancer (PC), race, age, and certain dietary
factors have been reported to increase the risk for
PC.2-7 Increased consumption of foods high in ani-
© 2004. From the Departments of Pediatrics (Kuvibidila) and Urol-
ogy (Gauthier, Rayford), Louisiana State University Health Sci-
ences Center, New Orleans, LA. Send correspondence and
reprint requests for J Natl MedAssoc. 2004;96:641-649 to: Solo
Kuvibidila, PhD, Department of Pediatrics; Division of Research,
Box T8-1; 1542 Tulane Ave., New Orleans, LA 70112, phone:
(504) 568-4561 or 504-896-2744; fax: (504) 568-3078; e-mail:
mal fat and an increased proportion of calories
from animal fat have also been associated with a
high risk for PC in all races.5 In contrast, certain
antioxidants, such as selenium and zinc, have been
suggested to play a protective role for PC.8,9
A number of clinical, epidemiological, and
experimental studies suggest that elevated body
iron stores increase the risk of cancer overall and,
specifically, cancer ofthe liver, lung, colon-rectum,
esophagus, gastrointestinal tract, and pancreas.'0-'3
Data collected during the first National Health
Assessment and Nutritional Examination Survey
(NHANES I) conducted in the United States
between 1971 and 1975 also suggested that moder-
ate elevations ofbody iron stores assessed by trans-
ferrin saturation (TS) above 40%, were associated
with increased risk and mortality from cancer.'4
There are two possible mechanisms by which
iron may increase the risk of cancer. The first is by
increasing the production of free radicals thought to
be carcinogenic and the second by regulating the
activity ofribonucleotide reductase, the rate-limiting
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
VOL. 96, NO. 5, MAY 2004 641
IRON STATUS AND RISK OF CANCER
enzyme in the DNA synthesis pathway and, hence,
cell proliferation.'5 16 Indeed, iron chelation by defer-
oxamine inhibits the proliferation oftumor cells and
normal lymphocytes, and also induces apoptosis.'6-18
There is a paucity of information on iron status
and risk of PC. Therefore, the present study was
designed to determine whether elevated body iron
stores defined as serum ferritin >300 pg/L and/or
TS>50% are associated with increased risk ofPC.
In the present study, we report for the first time that
there is a negative correlation between body iron
status and risk ofPC.
PATIENTS AND METHODS
The study involved 118 men-34 with newly
diagnosed and untreated PC and 84 without PC.
Ninety-one percent of the men with PC (n=3 1)
were African Americans, and 9% were caucasians.
In the non-PC (control) group, 61.9% (n=52) were
African Americans, 35.7% (n=30) were cau-
casians, and 2.38% (n=3) were other. The age
ranges were 49-75 and 49-78 years for PC patients
and controls, respectively. All men participated in
an ongoing PC screening and early detection pro-
gram at Louisiana State University Health Sciences
Center in New Orleans. Recommendation for tran-
srectal ultrasonography ofthe prostate was offered
to those participants whose prostate-specific anti-
gen (PSA) level was higher than 2.5 ng/mL for
definitive histopathological diagnosis or had an
abnormal digital rectal examination. All partici-
pants diagnosed with PC and included in the study
were diagnosed and treated by the senior author
(WR) between 1999 and 2001. PSA samples com-
prising the control group were chosen from a pool
of approximately 6,000 participants based on the
following criteria: a) PSA <2.5 ng/ml in whom the
likelihood ofhaving PC is very low (n=70); b) PSA
level >2.5 ng/ml, with a negative biopsy for PC
(n=10); c) men ages of49-78 years, and d) no spe-
cific symptoms or complaints at the time of study
entry. Since this was a retrospective study, no infor-
mation had been collected on the dietary intake of
iron or factors known to affect iron status, such as
smoking, or recent blood loss or donation. The
study and consent were approved by the Institution-
al Review Board of Louisiana State University
Health Sciences Center, and informed consent was
obtained from all participants prior to screening.
Various measurements were made on previously
frozen (-80°C) serum samples. PSA levels were
measured by the Bayer Immuno 1TM assay (Bayer
Corporation, Tarrytown, NY). Serum ferritin levels
were measured by enzyme immunoassay with com-
mercial kits purchased fromRAMCO (Houston, TX).
Serum iron andTIBC were measured by colorimetry
with kits purchased from Sigma (St. Louis, MO). Test
samples, standards, and controls were assayed in
duplicate according to manufacturer's recommenda-
tions. TS was calculated by dividing serum iron by
TIBC. Elevated body iron stores were defined as
serum ferritin above 300gg/Land TS >50%.12,19-20
Reduced body iron stores were defined as serum fer-
ritin less than 12 ig/L and TS <16%.2' In those men
with inflammation (see below), the threshold for
reduced body iron stores was defined as serum fer-
Table 1. Mean Age, PSA, and Blood Concentrations of Inflammatory Markers in Men
with and without Prostate Cancer
60.65 ± 1.2759.05 ± 0.89
PSA, ng/mL10.34 ± 1.23
1.52 ± 0.19
0.97 ± 0.050.855 ± 0.03
ACT, mg/L356 ± 96368 ± 8.52
5.63 ± 1.023.79 ± 0.65a
425 ± 19440 ± 16C
African Americans African Americans
56.46 ± 0.96
1.52 ± 0.19
0.864 ± 0.03
372 ± 11
4.14 + 0.98b
466 ± 25d
60.94 ± 1.27
10.73 ± 1.94
0.975 ± 0.053
361 ± 17.7
5.98 ± 1.097
427 ± 17.2
Values are mean ± SEM. Abbreviations: ACT=antichymotrypsin, AGP=a1-acid glycoprotein, CRP=C-reactive
protein, Cp=ceruloplasmin, PSA=prostate specific antigen. Samples sizes: a=83; b=51; c=71; d=41.
642 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATIONVOL. 96, NO. 5, MAY 2004
IRON STATUS AND RISK OF CANCER
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