Introduction: The aim of this article was to investigate the relationship between statins and the risk of different stages or grades of prostate cancer. Methods: A comprehensive literature search was performed for articles published until December 18, 2020, on the PubMed, Embase, and the Cochrane Library databases. The pooled relative risk (RR) and 95% confidence interval (CI) were then analyzed using the STATA.16.0 software. Results: A total of 588,055 patients from 14 studies were included in the analysis. We found that the use of statins expressed a significant correlation with a lower risk of advanced prostate cancer (RR = 0.81, 95% CI: 0.73–0.91; RR = 0.86, 95% CI: 0.75–0.99, respectively). However, no evidence suggested that the use of statins was beneficial for the prevention of localized prostate cancer incidence. Similarly, the pooled results also revealed no association between the use of statins and the risk of high-grade and low-grade prostate cancer. Conclusion: It has been found that the use of statins is associated with a lower risk of advanced prostate cancer but was not related to the risk of localized, low-grade, or high-grade prostate cancer.

1.
Sirtori
CR
.
The pharmacology of statins
.
Pharmacol Res
.
2014
;
88
:
3
11
. .
2.
Li
GM
,
Zhao
J
,
Li
B
,
Zhang
XF
,
Ma
JX
,
Ma
XL
,
The anti-inflammatory effects of statins on patients with rheumatoid arthritis: a systemic review and meta-analysis of 15 randomized controlled trials
.
Autoimmun Rev
.
2018
;
17
(
3
):
215
25
. .
3.
Bu
DX
,
Griffin
G
,
Lichtman
AH
.
Mechanisms for the anti-inflammatory effects of statins
.
Curr Opin Lipidol
.
2011
;
22
(
3
):
165
70
. .
4.
Koch
CA
,
Krabbe
S
,
Hehmke
B
.
Statins, metformin, proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and sex hormones: immunomodulatory properties?
Rev Endocr Metab Disord
.
2018
;
19
(
4
):
363
95
. .
5.
Cote-Daigneault
J
,
Mehandru
S
,
Ungaro
R
,
Atreja
A
,
Colombel
JF
.
Potential immunomodulatory effects of statins in inflammatory bowel disease
.
Inflamm Bowel Diseases
.
2016
;
22
(
3
):
724
32
.
6.
Owens
AP
 3rd
,
Mackman
N
.
The antithrombotic effects of statins
.
Annu Rev Med
.
2014
;
65
:
433
45
. .
7.
Iannelli
F
,
Lombardi
R
,
Milone
MR
,
Pucci
B
,
De Rienzo
S
,
Budillon
A
,
Targeting mevalonate pathway in cancer treatment: repurposing of statins
.
Recent Pat Anticancer Drug Discov
.
2018
;
13
(
2
):
184
200
. .
8.
Borgquist
S
,
Bjarnadottir
O
,
Kimbung
S
,
Ahern
TP
.
Statins: a role in breast cancer therapy?
J Intern Med
.
2018
;
284
(
4
):
346
57
. .
9.
American Cancer Society
.
Key statistics for prostate cancer [internet]
[cited 2020 Dec 31]. Available from: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.
10.
National Cancer Institute
.
Cancer stat facts: prostate cancer [internet]
[cited 2020 Dec 31]. Available from: https://seer.cancer.gov/statfacts/html/prost.html.
11.
Ferlay
J
,
Colombet
M
,
Mery
L
,
Pineros
M
,
Znaor
A
,
Soerjomataram
I
.
Global cancer observatory: cancer tomorrow
[cited 2020.12.31]. Available from: https://gco.iarc.fr/tomorrow.
12.
Emberson
J
.
Safety of statin therapy: meta-analysis of data on cancer from 166 000 participants in 25 randomised trials
.
Eur Heart J
.
2010
;
31
:
898
.
13.
Tan
P
,
Yang
L
,
Wei
S
,
Gao
L
,
Tang
Z
,
Wei
Q
.
Current evidence does not support the hypothesis that statin use reduces the risk of prostate cancer
.
J Urol
.
2016
;
195
(
4
):
e675
.
14.
Wang
K
,
Gerke
TA
,
Chen
X
,
Prosperi
M
.
Association of statin use with risk of gleason score-specific prostate cancer: a hospital-based cohort study
.
Cancer medicine
.
2019
;
8
(
17
):
7399
407
.
15.
Ho
W
,
Choo
DW
,
Wu
YJ
,
Chan
TF
,
Lin
ZF
.
Statin use and the risk of prostate cancer in ischemic heart disease patients in Taiwan
.
Clin Pharmacol Ther
.
2019
;
106
(
2
):
458
66
. .
16.
Allott
EH
,
Ebot
EM
,
Stopsack
KH
,
Gonzalez-Feliciano
AG
,
Markt
SC
,
Wilson
KM
,
Statin use is associated with lower risk of PTEN-null and lethal prostate cancer
.
Clin Cancer Res
.
2020
;
26
(
5
):
1086
93
. .
17.
Deeks
JJ
,
Dinnes
J
,
D’Amico
R
,
Sowden
AJ
,
Sakarovitch
C
,
Song
F
,
Evaluating non-randomised intervention studies
.
Health Technol Assess
.
2003
;
7
(
27
):
iii
x
, 1–173. .
18.
Stare
J
,
Maucort-Boulch
D
.
Odds ratio, hazard ratio and relative risk
.
Metod Zv
.
2016
;
13
:
59
67
.
19.
Zhang
J
,
Yu
KF
.
What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes
.
JAMA
.
1998
;
280
(
19
):
1690
1
. .
20.
Agalliu
I
,
Salinas
CA
,
Hansten
PD
,
Ostrander
EA
,
Stanford
JL
.
Statin use and risk of prostate cancer: results from a population-based epidemiologic study
.
Am J Epidemiol
.
2008
;
168
(
3
):
250
60
. .
21.
Chan
JM
,
Litwack-Harrison
S
,
Bauer
SR
,
Daniels
NA
,
Wilt
TJ
,
Shannon
J
,
Statin use and risk of prostate cancer in the prospective Osteoporotic Fractures in Men (MrOS) Study
.
Cancer Epidemiol Biomarkers Prev
.
2012
;
21
(
10
):
1886
8
. .
22.
Farwell
WR
,
D’Avolio
LW
,
Scranton
RE
,
Lawler
EV
,
Gaziano
JM
.
Statins and prostate cancer diagnosis and grade in a veterans population
.
J Natl Cancer Inst
.
2011
;
103
(
11
):
885
92
. .
23.
Fowke
JH
,
Motley
SS
,
Barocas
DA
,
Cookson
MS
,
Concepcion
R
,
Byerly
S
,
The associations between statin use and prostate cancer screening, prostate size, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer
.
Cancer Causes Control
.
2011
;
22
(
3
):
417
26
. .
24.
Jacobs
EJ
,
Newton
CC
,
Thun
MJ
,
Gapstur
SM
.
Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort
.
Cancer Res
.
2011
;
71
(
5
):
1763
71
. .
25.
Jacobs
EJ
,
Rodriguez
C
,
Bain
EB
,
Wang
Y
,
Thun
MJ
,
Calle
EE
.
Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort
.
Cancer Epidemiol Biomarkers Prev
.
2007
;
16
(
11
):
2213
7
. .
26.
Jespersen
CG
,
Norgaard
M
,
Friis
S
,
Skriver
C
,
Borre
M
.
Statin use and risk of prostate cancer: a Danish population-based case-control study
.
Cancer epidemiology
.
2014
;
38
(
1
):
42
7
.
27.
Kantor
ED
,
Lipworth
L
,
Fowke
JH
,
Giovannucci
EL
,
Mucci
LA
,
Signorello
LB
.
Statin use and risk of prostate cancer: results from the Southern Community Cohort Study
.
Prostate
.
2015
;
75
(
13
):
1384
93
. .
28.
Murtola
TJ
,
Tammela
TL
,
Lahtela
J
,
Auvinen
A
.
Cholesterol-lowering drugs and prostate cancer risk: a population-based case-control study
.
Cancer Epidemiol Biomarkers Prev
.
2007
;
16
(
11
):
2226
32
. .
29.
Murtola
TJ
,
Tammela
TL
,
Määttänen
L
,
Huhtala
H
,
Platz
EA
,
Ala-Opas
M
,
Prostate cancer and PSA among statin users in the finnish prostate cancer screening trial
.
Int J Cancer
.
2010
;
127
(
7
):
1650
9
. .
30.
Nordström
T
,
Clements
M
,
Karlsson
R
,
Adolfsson
J
,
Grönberg
H
.
The risk of prostate cancer for men on aspirin, statin or antidiabetic medications
.
Eur J Cancer
.
2015
;
51
(
6
):
725
33
. .
31.
Shannon
J
,
Tewoderos
S
,
Garzotto
M
,
Beer
TM
,
Derenick
R
,
Palma
A
,
Statins and prostate cancer risk: a case-control study
.
Am J Epidemiol
.
2005
;
162
(
4
):
318
25
. .
32.
Tan
N
,
Klein
EA
,
Li
J
,
Moussa
AS
,
Jones
JS
.
Statin use and risk of prostate cancer in a population of men who underwent biopsy
.
J Urol
.
2011
;
186
(
1
):
86
90
. .
33.
Hatano
K
,
Fujita
K
,
Nonomura
N
.
Application of anti-inflammatory agents in prostate cancer
.
J Clin Med
.
2020
;
9
(
8
):
1
27
.
34.
Chen
J
,
Zhang
B
,
Chen
D
,
Zhuang
W
.
The association of statin use with risk of kidney, bladder and prostate cancer: a systematic review and meta-analysis of cohort studies
.
Int J Clin Exp Med
.
2018
;
11
(
9
):
8873
.
35.
Tan
P
,
Wei
S
,
Tang
Z
,
Gao
L
,
Zhang
C
,
Nie
P
,
LDL-lowering therapy and the risk of prostate cancer: a meta-analysis of 6 randomized controlled trials and 36 observational studies
.
Sci Rep
.
2016
;
6
:
24521
. .
36.
Bonovas
S
,
Filioussi
K
,
Sitaras
NM
.
Statin use and the risk of prostate cancer: a metaanalysis of 6 randomized clinical trials and 13 observational studies
.
Int J Cancer
.
2008
;
123
(
4
):
899
904
. Available from: .
37.
Liu
A
,
Wu
Q
,
Guo
J
,
Ares
I
,
Rodríguez
JL
,
Martínez-Larrañaga
MR
,
Statins: adverse reactions, oxidative stress and metabolic interactions
.
Pharmacol Ther
.
2019
;
195
:
54
84
. .
38.
Alfaqih
MA
,
Allott
EH
,
Hamilton
RJ
,
Freeman
MR
,
Freedland
SJ
.
The current evidence on statin use and prostate cancer prevention: are we there yet?
Nat Rev Urol
.
2017
;
14
(
2
):
107
19
. .
39.
Papadopoulos
G
,
Delakas
D
,
Nakopoulou
L
,
Kassimatis
T
.
Statins and prostate cancer: molecular and clinical aspects
.
Eur J Cancer
.
2011
;
47
(
6
):
819
30
. .
40.
Bathaie
SZ
,
Ashrafi
M
,
Azizian
M
,
Tamanoi
F
.
Mevalonate pathway and human cancers
.
Curr Mol Pharmacol
.
2017
;
10
(
2
):
77
85
. .
41.
Dawe
DE
,
Mahmud
S
.
Biologic and epidemiologic evidence assessing if statins prevent prostate cancer
.
Can J Urol
.
2017
;
24
(
6
):
9081
8
.
42.
Miyazawa
Y
,
Sekine
Y
,
Kato
H
,
Furuya
Y
,
Koike
H
,
Suzuki
K
.
Simvastatin up-regulates annexin A10 that can inhibit the proliferation, migration, and invasion in androgen-independent human prostate cancer cells
.
Prostate
.
2017
;
77
(
4
):
337
49
. .
43.
Deng
JL
,
Zhang
R
,
Zeng
Y
,
Zhu
YS
,
Wang
G
.
Statins induce cell apoptosis through a modulation of AKT/FOXO1 pathway in prostate cancer cells
.
Cancer Manag Res
.
2019
;
11
:
7231
42
. .
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