Hypercholesterolemia and Prostate Cancer: A Hospital-Based Case–Control Study

Author(s): Lindsay Magura, Richelle Blanchard, Brian Hope, James R. Beal, Gary G.
Schwartz and Abe E. Sahmoun
Source: Cancer Causes & Control, Vol. 19, No. 10 (Dec., 2008), pp. 1259-1266
Published by: Springer
Stable URL: https://www.jstor.org/stable/40271828
Accessed: 15-10-2023 14:05 +00:00

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Cancer Causes Control (2008) 19:1259-1266
DOI 10.1007/sl0552-008-9197-7
ORIGINAL PAPER
Hypercholesterolemia and prostate cancer: a hospital-based
case-control study
Lindsay Magura * Richelle Blanchard * Brian Hope *
James R. Beai * Gary G. Schwartz * Abe E. Sahmoun
Received: 21 January 2008 /Accepted: 19 June 2008 /Published online: 13 August 2008
© Springer Science+Business Media B.V. 2008
Abstract
Objective High levels of serum cholesterol have been
proposed to increase the risk of prostate cancer but the
epidemiologie evidence is limited.
Methods We conducted a hospital-based case-control
study in Fargo, ND, USA, to examine the association
between hypercholesterolemia and prostate cancer. Cases
were men with incident, histologically confirmed prostate
cancer. Controls were men without clinical cancer who
were seen at the same hospital for an annual physical exam.
Demographic and clinical data were abstracted from
patients' medical charts.
Results From a patient population aged 50 to 74 years old,
we obtained data on 312 White cases and 319 White con-
trols. Hypercholesterolemia was defined as total cholesterol
greater than 5.17 (mmol/1). Univariate logistic regression
showed a significant association between hypercholester-
olemia and prostate cancer (odds ratio (OR) = 1.64, 95%
confidence interval (CI): 1.19-2.27). This association
L. Magura • R. Blanchard • B. Hope
University of North Dakota School of Medicine and Health
Sciences, Grand Forks, ND, USA
J. R. Beai
Department of Family and Community Medicine,
University of North Dakota School of Medicine
and Health Sciences, Grand Forks, ND, USA
G. G. Schwartz
Department of Cancer Biology, Wake Forest University School
of Medicine, Winston-Salem, NC, USA
A. E. Sahmoun (IS!)
Department of Internal Medicine, University of North Dakota
School of Medicine and Health Sciences, 1919 Elm Street North,
Fargo, ND 58102, USA
e-mail: asahmoun@medicine.nodak.edu
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changed only slightly after adjustment for age, family his-
tory of prostate cancer, body mass index, type 2 diabetes,
smoking, and multivitamin use (OR = 1.58, 95% CI: 1.11-
2.24). A significant association was found between low
HDL and prostate cancer (OR = 1.57, 95% CI: 1.04-2.36).
High LDL was associated with a 60% increased risk for
prostate cancer (OR = 1.60, 95% CI: 1.09-2.34). Com-
pared to never smokers, current smokers had an 84%
increased risk for prostate cancer (OR = 1.84, 95% CI:
1.09-3.13).
Conclusion This study adds to recent evidence that
hypercholesterolemia may increase the risk of prostate
cancer in white men.
Keywords Prostate cancer • Hypercholesterolemia •
Lipid profiles • Epidemiology • Statins
Introduction
Prostate cancer is the most commonly diagnosed (non-skin)
cancer among men in the United States (U.S.), accounting
for approximately 186,320 new cases and 28,660 deaths in
2008 [1]. Other than increasing age, black race, and family
history, risk factors for prostate cancer have not been
consistently identified [2-6].
Evidence for a role of cholesterol in prostate disease
dates at least to 1942 when Swyer reported increased
cholesterol content of prostatic adenomas relative to nor-
mal tissue [7]. Since then, the results of many laboratory
studies support a relationship between cholesterol in
prostate tissues or secretions and benign and malignant
prostate growth. Other studies suggest that the addition of
cholesterol to animal diets promotes oxidative stress and
carcinogenesis [8]. Furthermore, the commonly used
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1260 Cancer Causes Control (2008) 19:1259-1266
statins, lovastatin, fluvastatin, and simvastatin, induce
apoptosis and inhibit the proliferation of prostate cancer
cell lines in culture. [9]. A significant chemopre venti ve
effect of statins on prostate cancer also has been shown in
vivo [10].
Despite provocative laboratory evidence, analytical
epidemiological studies of hypercholesterolemia and
prostate cancer in men are inconclusive. Graaf et al.
examined overall cancer incidence in 300,000 residents of
eight Dutch cities and correlated this with prescriptions for
cardiovascular drugs. They found a 63% reduction in the
risk of prostate cancer [1 1]. In a large case-control study of
1,294 cases and 1,451 controls, Bravi et al. [12] found a
significant increased risk of prostate cancer among hyper-
cholesterolemic men (odds ratio (OR) =1.51 [1.23-1.85]).
These authors also reported an increased risk for gallstones,
which are often related to hypercholesterolemia. Con-
versely, other studies have failed to show any association
[13-15].
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors (commonly known as "statins") are
cholesterol-lowering drugs that have been widely used to
reduce the risk of cardiovascular disease. Three large pro-
spective studies: Cancer Prevention Study II Nutrition
Cohort [16], California Men's Health Cohort Study [17], and
a case-control study nested in the Finnish population [18],
investigated the association between use of statin drugs and
prostate cancer. Along with work in the Health Professionals
Follow-up Study reported by Platz et al. [19], four pro-
spective studies support an inverse association between
statin use and advanced prostate cancer. Despite the differ-
ent characteristics of the four study settings, an inverse
association between longer-term use of statins and prostate
cancer was observed in each, with point estimates of 0.26
[19], 0.60 [16], 0.57 [17] and 0.75 [18]. A small case^control
study [20] of 100 men with prostate cancer recruited upon
referral for biopsy found a 62% reduction in the risk of
prostate cancer (OR = 0.38 [0.21-0.69]) with statin use.
Lastly, a large population-based study reported by Teemu
et al. [21] showed no evidence for reduced overall prostate
cancer risk among users of cholesterol-lowering drugs, but
found a decreased risk of advanced cancer among statin
users (atorvastatin, lovastatin, and simvastatin (OR = 0.61
[0.37-0.98]; OR = 0.61 [0.43-0.85]; and OR = 0.78
[0.61-1.01], respectively). Bonovas et al. [22] examined
statin use in relation to both total prostate cancer and the
more clinically important advanced prostate cancer via a
detailed meta-analysis of the epidemiologie literature. There
was no evidence of an association between statin use and
total prostate cancer among observational studies (relative
risk (RR) = 0.89 [0.65-1.24]) or among randomized con-
trolled trials (RR = 1.06 [0.93-1.20]). Conversely,
synthesis of the available reports that had specifically
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examined statin use in relation to advanced prostate cancer
indicated a protective association (RR = 0.77 [0.64-0.93]).
The aim of this study was to provide additional data to
address the question of hypercholesterolemia and risk of
prostate cancer.
Methods
We performed a retrospective analysis of medical charts of
patients newly diagnosed with prostate cancer between
2004 and 2006. Cases were identified from the cancer
registry of Meritcare hospital, North Dakota, USA. Con-
trols were identified from the primary care database of the
same hospital. This facility serves the Fargo Metropolitan
Area comprising all of Cass County, North Dakota and
Clay County, Minnesota. Its population, according to the
2006 estimate, is approximately 200,000. The majority
(96%) of the population served in this area is White. The
North Dakota Cancer Registry releases annual cancer sta-
tistics when the registry's data is estimated to be 95%
complete for any given cancer-reporting year. The study
was approved by the Institutional Review Boards of the
Hospital and the University of North Dakota.
Study design
Data on age, family history of prostate cancer, histology,
stage at diagnosis (TNM system), body mass index, occu-
pation, smoking status, Prostate Specific Antigen (PSA),
Gleason score, lipid profiles, statins use, non-steroidal anti-
inflammatory use (NSAIDs), comorbidities, and multivita-
min use were abstracted using electronic records and
medical charts. Covariates information was obtained for the
period prior to diagnosis for cases and prior to exam for
controls. Inclusion and exclusion criteria were as follows:
The inclusion criteria for cases were men with incident,
histologically confirmed prostate cancer as a primary site
with cancer diagnosed between 2004 and 2006 using a
pathology report present in the medical records, age
between 50 and 74 and date of lipid profiles tests within a
year prior to the diagnosis of prostate cancer. The exclu-
sion criteria included diagnosis of any cancer other than
primary prostate cancer and race other than Caucasian
(excluded because of small numbers [<6% of residents of
Fargo-Moorhead are non-Caucasian]).
The inclusion criteria for controls were men who had an
annual physical exam between 2004 and 2006 at the same
hospital as cases, age between 50 and 74, without cancer
seen at the same hospital as cases, and date of lipid profiles
tests within a year of the annual physical exam. The
exclusion criteria included diagnosis of any cancer, pros-
tate specific antigen >4 ng/1 (in order to exclude
Cancer Causes Control (2008) 19:1259-1266 1261
undiagnosed prostate cancer), and race other than
Caucasian.
Exposure definition
We used the National Cholesterol Education Program
(NCEP) definition of hypercholesterolemia as total cho-
lesterol greater than 5.17 (mmol/1) [23]. For comparison
with previous studies, the prevalence of hypercholesterol-
emia was also calculated using a cutpoint of >6.2 (mmol/1).
Statin use was classified as hydrophobic only users
(lovastatin, simvastatin, atorvastatin, or fluvastatin) or
hydrophilic only users (pravastatin or rosuvastatin) as
reported elsewhere [24]. No other lipid lowering agents
were in use among this study population.
Factors that may confound the association between
cholesterol and prostate cancer, such as family history of
prostate cancer, body mass index, statins use, smoking,
type 2 diabetes, and multivitamin use were included in our
analyses as potential confounders.
Statistical analyses
Odds ratios (OR) and 95% confidence intervals (CI) were
estimated using unconditional multiple logistic regression,
including terms for age, family history of prostate cancer,
body mass index (BMI), smoking, type 2 diabetes and mul-
tivitamin use. All /7-values are two-sided. All two-way
interactions involving hypercholesterolemia were assessed.
Tests for interaction were assessed by introducing a multi-
plicative term between the two variables in the multivariable
model using a Wald test. Analyses were performed using
SAS software V9.1.3 (SAS Institute, Cary, NC, USA).
Results
This study included 312 men with newly diagnosed pros-
tate cancer and 319 controls. The median age (range) was
63.5 (50-74) years for men with prostate cancer and 64
(50-74) years for controls. Prostate cancer patients had a
significantly higher prevalence of family history of prostate
cancer (32% vs. 8%, respectively; p < .0001) (Table 1).
More than 50% of the patients had a BMI >24.99 (kg/m2).
Median PSA in prostate cancer patients was 5.8 (0.4-297).
The majority (65%) had a low Gleason grade (<7). All
prostate cancers were adenocarcinomas. Forty-nine percent
of the controls reported taking multivitamins versus 39% of
cases (p < .01).
Univariate logistic regression showed a significant
association between hypercholesterolemia and prostate
cancer (OR = 1.64 [1.19-2.27]). Current smokers had an
85% increased odds for prostate cancer versus never
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smokers (OR = 1.85 [1.14-3.01]) (Table 2). Current
multivitamin users had a 33% reduced odds for prostate
cancer compared to patients who reported being non-users
(OR = 0.67 [0.49-0.92]). Multivariate models adjusted for
age, family history of prostate cancer, BMI, smoking sta-
tus, type 2 diabetes, and multivitamin use. The logistic
regression analysis showed a significant association
between hypercholesterolemia (>5.17 mmol) and prostate
cancer (OR = 1.58 [1.11-2.24]) (Table 2). "Borderline
high" cholesterol (5.17-6.19 mmol/1) was significantly
associated with prostate cancer (OR = 1.59 [1.08-2.34])
while "high" cholesterol (>6.20) increased the risk for
prostate cancer but not significantly (OR = 1.54 [0.87-
2.72]). Adjusting for statin use did not alter the association
between hypercholesterolemia and prostate cancer
(OR = 1.56 [1.09-2.23]). Several studies have examined
risk by stratifying cases into high and low Gleason grade
(>7 and <7, respectively). We found that hypercholester-
olemia is associated with an increased risk of high Gleason
grade (Gleason >7) prostate cancer (OR =1.15 [0.74-
1.78]; p = 0.53) compared to low Gleason grade but the
risk did not differ significantly from 1.
The multivariable model showed a significant associa-
tion between low HDL and prostate cancer (OR = 1.57
[1.04-2.36]). High LDL was associated with a 60%
increased risk for prostate cancer (OR = 1.60 [1.09-2.34]).
Current smokers had an 84% increased risk for prostate
cancer (OR = 1.84 [1.09-3.13]). Multivitamin users had a
34% reduced risk for prostate cancer (OR = 0.66 [0.47-
0.93]). NSAID use significantly reduced the risk for pros-
tate cancer (OR = 0.44 [0.31-0.62]). Adjusting for
smoking, multivitamins use, and NSAID use individually
or together did not modify significantly the association
between hypercholesterolemia and prostate cancer results.
Tests for interaction between hypercholesterolemia and
smoking, multivitamin use and NSAIDS were not signifi-
cant (p = 0.97, 0.83, 0.18, respectively).
Discussion
We found a significant association between hypercholes-
terolemia and prostate cancer. Furthermore, a significant
association was found between low HDL and prostate can-
cer, and high LDL was associated with a significantly
increased risk for prostate cancer. Total cholesterol is the
combination of LDL, HDL, and very low-density
lipoproteins.
These data are in agreement with the findings reported by
Bravi et al. [13] who found a significant association between
hypercholesterolemia and prostate cancer (OR =1.51
[1.23-1.85]). However, this study did not include statin use
or any other lipid profiles. A recent prospective study of 862
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1262 Cancer Causes Control (2008) 19:1259-1266

n%n%
Variables Cases Controls p-value
Table 1 Distribution of 312 cases of newly diagnosed prostate cancer and 319 controls according to demographic and clinical characteristics

Age
50-54(years)
29 9 31 0.98
10
55-59 66 21 66 21
60-64
65-69 67
70 22
22 74
66 23
21
70-74
Body Mass80Index
26 (kg/m2)
82 26 0.42
Normal
Overweight 30 9 31 10
Obese 15512750 41174
11454
36
Father 35 311110139 43
Family history of prostate cancer (n = 126) (n = 99) (n = 27) <0.0001
Brother(s)
Grandfather 3 1 1 0.3
Father and a brother 12 4 3 0.4
None 213 68
Smoking 292 92
Cousin(s) or Uncle(s) 18 6 1 0.3
status 0.03
Current 56 18 34 11
Former 126 42
40 146
139 46
44
Occupation
Never 130
Farmer 54 17 59 0.7
18
Non-farmer 258 83 260 82
Multi vitamins
Yes 122 39 156use
490.01
No 190
Clinical 61 163
prostate 51<0.0001
cancer
Prostate-specific antigen (ng/ml) 5.8 (0.4-297)a 1.0 (0.09-3.9)

Low grade (<7) 203 65

Gleason scores

Tl 102 33
High grade (>7) 109 35

T4 2 1-
T2
T3 175
33 56
11
Stage disease at diagnosis

Total cholesterol
Lipid profiles (mmol/1)
0.01
Desirable (<5. 17) 174 56 215 67
High(>6.20) 35 11 29(HDL)
9 0.25
Borderline high (5.17-6.19) 103 33 75 24
High-density lipoproteins
Low(<1.03) 55 18 56 17
Normal ( 1. 03 < 1.55) 182 58 203 64
High(>1.55) 75 24 60 19
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Cancer Causes Control (2008) 1 9: 1 259-1 266 1 263

n % n %
Variables Cases Controls /?-value
Table 1 continued

Low-density lipoprotein (LDL) 0.007

Optimal (<2.58) 107 35 152 48
Near/above optimal (2.58-3.33) 100 33 95 30
Borderline high (3.36-^.11) 66 22 43 14
High
Very (4.13-4.88) 28 5
9 20
16 62
Triglycérides
Normal (<1. 69) 189 61 192 600.9
high (>4.91)
Borderline high (1.69-2.25) 68 22 74 23
High/very high (>2.26) 54 17 53 17
Statins use
Hydrophilicb(n = 92) (n =
7 102 108)
2 6322 0.42
None 220 71 211 66
Hydrophobie0 85 27
Hypertension 169 54 190 60 0.17
Comorbidities

Type 2 diabetes 48 15 81 25 0.002

Benign prostatic hyperplasia 25 8 52 16 0.002
Yes 149
No 163 52
48 228 71
Non-steroidal anti-inflammatory 0.0001
91 29
a Median (range)
b Hydrophilic: Pravastatin or rosuvastatin

c Hydrophobie: Lovastatin, simvastatin, atorvastatin, or fluvastatin

patients in four urologie centers in Austria performed lipid
and prostate-specific antigen (PSA) analysis and digital
rectal examination (DRE) on all patients at the initial visit
[25]. The patients then were divided among three groups
after analyses. The patients with prostate cancer had a sta-
tistically significant (p = 0.00001) elevated cholesterol-to-
high-density lipoprotein (HDL) ratio compared with men in
whom no cancer was found after two biopsies. The mean
triglycéride levels also were higher in the men with prostate
cancer. It was concluded that higher cholesterol levels
associated with lower levels of HDL could be a risk factor
for prostate cancer.
Our findings also are consistent with those of two recent
Nordic studies which reported a significant association
(adjusted RR = 3.0 [1.2-7.3]) than in lighter men
(RR = 1 .8 [0.7^.7]). In a recent study, Tuohimaa et al. [28]
found that men with BMI in the highest quartile (>28 kg/m2)
and low serum level of 25-Hydroxy vitamin D (<40 nmol/1)
had an increased risk for prostate cancer (OR = 2.28;
p < 0.01) compared with men with intermediate levels of
vitamin D (40-60 nmol/1) and BMI (<28 kg/m2). When a
low vitamin D level was present simultaneously with high
BMI, high SBP, and low HDL, the OR was 8.03 (p = 0.005)
when compared with men with a normal level of vitamin D
and no metabolic syndrome factors at risk level. They con-
cluded that the metabolic syndrome substantially increased
the prostate cancer risk especially in the presence of hypo-
vitaminosis D.

between the metabolic syndrome and increased risk of
prostate cancer [26, 27]. Metabolic syndrome is a constel-
lation of conditions including type 2 diabetes, obesity, high
blood pressure, a poor lipid profile with elevated LDL, low
HDL, and elevated triglycérides that place people at high risk
for coronary artery disease. The association between meta-
bolic syndrome and risk of prostate cancer was stronger
among overweight and obese men with a BMI >27 kg/m2
In a stratified analysis, we found that low serum HDL
increased the risk for prostate cancer among overweight
and obese men but was not significant. It is known that low
HDL is related to increased levels of several cancer pro-
moting hormones (e.g., androgens, estrogens, insulin, and
IGF-I) [29-31]. Our association may reflect the relative
importance and mutual dependence of different disease
pathways in prostate tumors. Hammarsten et al. [32] found

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1264 Cancer Causes Control (2008) 19:1259-1266
Table 2 Univariate and multivariable logistic regression of newly Several studies, but not all [33, 34], have shown that a
diagnosed prostate cancer patients (n = 312) and controls (n = 319) diet low in vegetables may be a risk factor for prostate
between 2004 and 2006
cancer [35-37]. Dietary data was not available in the
Variable Univariate Multivariable patients' charts and we were thus unable to evaluate diet
OR 95% CI OR 95% CI per se. However, data on multivitamin use was available.
Our study found that multivitamin users were significantly
Family history of prostate cancer less likely to be diagnosed with prostate cancer than non-
No Reference Reference users. Conversely, some studies have reported that men
Yes 5.03 3.17-7.97 4.99 3.11-7.98 taking high levels of multivitamins along with other sup-
Body Mass Index plements have an increased risk of advanced and fatal
Normal (<25 kg/m2) Reference Reference prostate cancer [38, 39]. The use of multivitamins in our
Overweight/obese 1.01 0.60-1.72 1.04 0.58-1.85 study was self-reported and therefore subject to underes-
(>25 kg/m2) timation as well as overestimation. This would act to bias
Type 2 diabetes the association toward the null.
No Reference Reference The prevalence of smokers in North Dakota is among
Yes 0.53 0.36-0.79 0.56 0.36-0.86 the highest in the nation [40]. Smokers are known to be at
Smoking status risk for several vitamin deficiencies including vitamin D
Never Reference Reference deficiency, which has been implicated in the etiology of
Former 1.02 0.73-1.43 1.10 0.77-1.59 prostate cancer [41]. Both positive and negative findings
Current 1.85 1.14-3.01 1.84 1.09-3.13 for supplement use in prostate cancer have been reported
Multivitamins use [42]. We found that current smokers were less likely to be
No Reference Reference multivitamin users and they were significantly at increased
Yes 0.67 0.49-0.92 0.66 0.47-0.93 risk for prostate cancer. Smoking has been implicated, but
Total cholesterol (mmol/1) not conclusively, in the promotion of clinical prostate
Normal (< 5.17) Reference Reference cancer [43, 44].
High(>5.17) 1.64 1.19-2.27 1.58 1.11-2.24 Observational studies have raised the possibility that the

High-density lipoproteins use of statins may decrease the risk of prostate cancer. A
Normal or High (>1.03) Reference Reference large case-control study was conducted on 443,805
Low(<1.03) 1.37 0.93-2.00 1.57 1.04-2.36 patients cared for at 10 Veterans Administration Medical
Low-density lipoprotein Centers (VAMCs) in four states, 26,139 of whom were
Normal (<3.33) Reference Reference diagnosed with prostate cancer [45]. Statin use prior to the
High(>3.36) 1.74 1. 22-2 .48 1.60 1.09-2.34 diagnosis of prostate cancer was associated with a signifi-
Triglycérides cant protective effect for prostate cancer (OR = 0.46
Normal (<1.69) Reference Reference [0.45-0.48]) after controlling for age, body mass index,

High (> 1.69) 0.98 0.72-1.35 1.09 0.77-1.53 smoking, diabetes, and race. In our study, statin use
Statin use decreased the risk for prostate cancer but was not signifi-
No Reference Reference cant. Statins use did not alter the association between

Yes 0.82 0.58-1.14 0.97 0.67-1.41
Age was included in the multivariable logistic regression as a con-
tinuous variable. Other variables included were: family history of
prostate cancer, BMI, type 2 diabetes, smoking, multivitamin use, and
statins use. Each of the lipid panels HDL, LDL, triglycérides, and
cholesterol were used in the model one at a time. Adjusting for statins
use did not alter the association between hypercholesterolemia and
prostate cancer (OR = 1.56; 95% CI 1.09-2.23)
that the lower the HDL levels the higher the Gleason score
is in patients diagnosed with prostate cancer.
We did not adjust for individuals with a previous diag-
nosis of hyperlipidemia regardless of the current lipid
levels. However, it is important to note that if men were
diagnosed with hyperlipidemia but were treated, this would
underestimate the risk for hyperlipidemia, as lipid levels
would have been lowered by treatment.
hypercholesterolemia and prostate cancer in our study.
It is important to examine how the present results may
be influenced by common biases in case-control studies.
Hospital controls may differ from the general population in
several aspects as regards medical history and exposure.
We used controls who came for an annual physical exam at
the departments of internal and family medicine within the
same hospital covering the same area. However, because
the controls were not biopsied, and because subclinical
prostate cancer is common, this could introduce bias in that
the controls would contain a percentage of undiagnosed
cases. This would produce a bias toward the null. This
study may also have been subject to detection bias. For
example, because cholesterol levels may exacerbate serum
levels of testosterone [46], which is known to increase
serum PSA [47], it is conceivable that some cases of

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Cancer Causes Control (2008) 19:1259-1266 1265
prostate cancer may have gone undetected since they did
not produce elevated levels of PSA. Furthermore, the
prevalence of high cholesterol in our control group (33%)
was similar to that of the general population of North
Dakota (35%) as reported in the Behavioral Risk Factors
Surveillance System [48]. Finally, it is possible that the
opportunity to undergo PSA screening is higher in hyper-
cholesterolemia patients in theory; however this appears
unlikely since high cholesterol is not yet conclusively
linked to prostate cancer.
Because cholesterol evaluations are a part of routine
physical exams, we assume that most men had their cho-
lesterol checked regularly during their annual physical
exam. Furthermore, the prevalence of overweight and
obesity is high in the area served by the facility; most men
older than 50 are also recommended lipid profiles during
the annual physical exam. This is an important consider-
ation because, in theory, it is possible that our study
population is over-represented with men previously diag-
nosed with hyperlipidemia which would bias the
association between prostate cancer and cholesterol levels.
We think this is unlikely because >90% of North Dakotans
over 55 years of age report having their cholesterol
checked within the last five years [49].
The majority (68%) of North Dakota men older than
50 years reported they had visited a doctor for a routine
checkup in 2004 [49]. This prevalence could be higher as
the facility in our study is located in an urban area. Those
considered as hyperlipidemic by the NCEP definition, the
percent currently receiving medical therapy, is 17%. If a
person was previously diagnosed as hyperlipidemic but
was now maintaining adequate lipid levels that would
underestimate the risk for prostate cancer.
Restricting the controls to men with PSA <4 ng/ml in
order to rule out undiagnosed prostate cancer may have
introduced bias with respect to factors that influence PSA,
such as inflammation. That is, by limiting PSA, the
control group is depleted of not only occult prostate
cancer, but also of BPH and asymptomatic prostatitis,
whereas no such restriction is made on the cases. How-
ever, information has been collected on the prevalence of
BPH in both cases and controls. Furthermore, adjusting
for BPH in the multivariable model did not significantly
alter the association between hypercholesterolemia and
prostate cancer.
Cinci et al. [50] showed that androgen suppression can
induce hypercholesterolemia in animals. Moorjani et al.
[51] showed that androgen suppression can induce hyper-
cholesterolemia in humans. Therefore, it is possible that
hypercholesterolemia was a consequence of prostate cancer
and not the cause. Because androgen-suppression therapy
is usually applied later in the natural history of prostate
cancer (e.g., after prostatectomy has failed), it is unlikely
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that this form of "reverse causality" is responsible for the
association we observed.
In conclusion, this study found additional evidence for
an association between hypercholesterolemia and incident
prostate cancer in white men. Because hypercholesterol-
emia is common and is preventable, larger prospective
population-based studies are warranted.
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