Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Emma H. Allott; Laura Farnan; Susan E. Steck; Lenore Arab; L. Joseph Su; Merle Mishel; Elizabeth T.H. Fontham; James L. Mohler; Jeannette T. Bensen

doi:10.1158/1055-9965.EPI-15-0631

DOI: 10.1158/1055-9965.EPI-15-0631 Published April 2016

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Table 1.

Demographic and tumor characteristics of CA and AA prostate cancer cases in PCap

	CA (n = 1,012)	AA (n = 918)	P
Age at diagnosis, mean (SD)	64 (8)	62 (8)	<0.0001
Site
North Carolina	479 (47)	448 (49)	0.519
Louisiana	533 (53)	470 (51)
Clinical stage
T1	559 (55)	509 (55)	0.926
T2–T4	453 (45)	409 (45)
PSA (ng/mL), median (IQR)	5.2 (4.1–7.5)	6.2 (4.5–10.7)	<0.0001
Biopsy Gleason sum
≤3+4	829 (82)	702 (77)	0.006
≥4+3	180 (18)	208 (23)
Aggressive prostate cancer
Low/intermediate	861 (85)	725 (79)	<0.0001
High	151 (15)	193 (21)
Prostate cancer screening frequency
Never	116 (11)	328 (36)	<0.0001
≤1 test per year	386 (38)	377 (75)
>1 test per year	510 (50)	123 (25)
Family history of prostate cancer (first-degree relative)^a
No	706 (75)	608 (72)	0.122
Yes	232 (25)	236 (28)
Education
Less than high school	94 (9)	265 (29)	<0.0001
High school graduate	212 (21)	258 (28)
College graduate or some college	706 (70)	394 (43)
Income^b
<$20,000	91 (10)	273 (32)	<0.0001
$20,000–$50,000	268 (29)	327 (39)
$50,000–$80,000	229 (25)	137 (16)
>$80,000	337 (36)	105 (12)
Smoking status
Never	367 (36)	283 (31)	<0.0001
Former	551 (54)	441 (48)
Current	94 (9)	194 (21)
BMI (kg/m²)
<30	635 (63)	558 (61)	0.375
≥30	377 (37)	360 (39)
Charlson comorbidity index
0	542 (54)	436 (47)	0.008
≥1	470 (46)	482 (53)
Cardiovascular disease
No	821 (81)	791 (87)	0.001
Yes	187 (19)	118 (13)
Diabetes
No	842 (84)	674 (74)	<0.0001
Yes	166 (16)	239 (26)
Dietary cholesterol intake (mg/day), median (IQR)	262 (180–355)	302 (206–439)	<0.0001
Percent saturated fat intake, mean (SD)	11.2 (2.7)	10.0 (2.6)	<0.0001
Nonstatin cholesterol-lowering drug use
None	842 (83)	844 (92)	<0.0001
Niacin/fibrate/ezetimibe	170 (17)	74 (8)

Abbreviation: IQR, interquartile range.

↵^aFamily history was missing for 74 CA and 74 AA men.
↵^bIncome was missing for 12 CA and 31 AA men, whereas 75 CA and 45 AA men refused to answer this question.

Table 2.

Demographic and tumor characteristics of statin users and nonusers in PCaP

	Statin nonusers (n = 1,205)	Statin users (n = 725)	P
Age at diagnosis, mean (SD)	62 (8)	65 (7)	<0.0001
Race
CA	604 (50)	408 (56)	0.009
AA	601 (50)	317 (44)
Site
North Carolina	602 (50)	325 (45)	0.029
Louisiana	603 (50)	400 (55)
Clinical stage
T1	679 (56)	389 (54)	0.249
T2–T4	526 (44)	336 (46)
PSA, median (IQR)	5.8 (4.3–9.8)	5.3 (4.1–7.6)	<0.0001
Biopsy Gleason sum
≤3 + 4	941 (79)	590 (82)	0.101
≥4 + 3	256 (21)	132 (18)
Aggressive prostate cancer
Low/intermediate	972 (81)	614 (85)	0.025
High	233 (19)	111 (15)
Prostate cancer screening frequency
Never	278 (23)	82 (11)	<0.0001
≤1 Test per year	365 (30)	260 (36)
>1 Test per year	562 (47)	383 (53)
Family history of prostate cancer (first-degree relative)^a
No	811 (73)	503 (75)	0.214
Yes	304 (27)	164 (25)
Education
Less than high school	234 (19)	125 (17)	0.320
High school graduate	299 (25)	171 (24)
College graduate or some college	672 (56)	428 (59)
Income^b
<$20,000	238 (22)	126 (19)	0.331
$20,000–$50,000	361 (33)	234 (35)
$50,000–$80,000	221 (20)	145 (22)
>$80,000	284 (25)	158 (24)
Smoking status
Never	407 (34)	243 (34)	<0.0001
Former	585 (49)	407 (56)
Current	213 (18)	75 (10)
BMI (kg/m²)
<30	793 (66)	400 (55)	<0.0001
≥30	412 (34)	325 (45)
Charlson comorbidity index
0	697 (58)	281 (39)	<0.0001
≥1	508 (42)	444 (61)
Cardiovascular disease
No	1,104 (92)	508 (71)	<0.0001
Yes	95 (8)	210 (29)
Diabetes
No	1,022 (85)	494 (69)	<0.0001
Yes	179 (15)	226 (31)
Dietary cholesterol intake (mg/day)	288 (198–406)	269 (179–368)	0.0001
Percent saturated fat intake, mean (SD)	10.6 (2.7)	10.7 (2.7)	0.811
Nonstatin cholesterol-lowering drug use
None	1,123 (93)	563 (78)	<0.0001
Niacin/fibrate/ezetimibe	82 (7)	162 (22)

Abbreviation: IQR, interquartile range.

↵^aFamily history missing for 90 statin nonusers and 58 statin users.
↵^bIncome was missing for 27 statin nonusers and 16 statin users, whereas 74 statin nonusers and 46 statin users refused to answer this question.

Table 3.

Associations between statin use, dose and type, and prostate cancer aggressiveness, overall and stratified by race

	All			CA			AA
	n, cases (aggressive)	OR^a (95% CI)	OR^b (95% CI)	n, cases (aggressive)	OR^a (95% CI)	OR^b (95% CI)	n, cases (aggressive)	OR^a (95% CI)	OR^b (95% CI)
Statin use
No use	1,205 (233)	1.00 (ref)	1.00 (ref)	604 (99)	1.00 (ref)	1.00 (ref)	601 (134)	1.00 (ref)	1.00 (ref)
Use	725 (111)	0.68 (0.53–0.87)	0.74 (0.56–0.96)	408 (52)	0.65 (0.45–0.93)	0.64 (0.44–0.95)	317 (59)	0.73 (0.51–1.03)	0.84 (0.58–1.21)
Statin dose^c
No use	1,205 (233)	1.00 (ref)	1.00 (ref)	604 (99)	1.00 (ref)	1.00 (ref)	601 (134)	1.00 (ref)	1.00 (ref)
Low/normal	306 (45)	0.65 (0.45–0.92)	0.70 (0.49–1.01)	180 (24)	0.68 (0.42–1.11)	0.66 (0.40–1.09)	126 (21)	0.64 (0.38–1.06)	0.74 (0.43–1.26)
High	419 (66)	0.70 (0.52–0.95)	0.76 (0.55–1.04)	228 (28)	0.62 (0.39–0.98)	0.63 (0.39–1.01)	191 (38)	0.79 (0.53–1.19)	0.90 (0.59–1.38)
Statin type^d
No use	1,205 (233)	1.00 (ref)	1.00 (ref)	604 (99)	1.00 (ref)	1.00 (ref)	601 (134)	1.00 (ref)	1.00 (ref)
Hydrophilic	132 (16)	0.53 (0.31–0.91)	0.56 (0.32–0.99)	81 (8)	0.48 (0.22–1.05)	0.45 (0.20–1.00)	51 (8)	0.62 (0.29–1.36)	0.72 (0.32–1.62)
Lipophilic	591 (94)	0.71 (0.54–0.92)	0.77 (0.58–1.02)	327 (44)	0.69 (0.46–1.02)	0.69 (0.46–1.04)	264 (50)	0.74 (0.51–1.07)	0.86 (0.58–1.27)

↵^aAdjusted for age only.
↵^bAdjusted for age, race (except for analyses stratified by race), site, BMI, cholesterol intake, percent saturated fat intake, smoking status, and prostate cancer screening frequency.
↵^cLow/normal dose ≤20 mg simvastatin or equivalent; high dose > 20 mg simvastatin or equivalent.
↵^dHydrophilic = rosuvastatin and pravastatin; lipophilic = atorvastatin, simvastatin, lovastatin, and fluvastatin.

Table 4.

Associations between statin use and prostate cancer aggressiveness, stratified by prostate cancer screening frequency

	n, cases (aggressive)	OR^a (95% CI)	OR^b (95% CI)
Never screened
Statin nonusers	278 (87)	1.00 (ref)	1.00 (ref)
Statin users	82 (23)	0.81 (0.47–1.41)	0.79 (0.45–1.39)
≤ 1 Screening tests per year
Statin nonusers	365 (61)	1.00 (ref)	1.00 (ref)
Statin users	260 (35)	0.67 (0.42–1.07)	0.66 (0.41–1.06)
> 1 Screening tests per year
Statin nonusers	562 (85)	1.00 (ref)	1.00 (ref)
Statin users	383 (53)	0.79 (0.54–1.15)	0.78 (0.53–1.15)

↵^aAdjusted for age only.
↵^bAdjusted for age, race, site, BMI, cholesterol intake, percent saturated fat intake, and smoking status.

Table 5.

Associations between statin use and prostate cancer aggressiveness, stratified by smoking status

	n, cases (aggressive)	OR^a (95% CI)	OR^b (95% CI)
Never smokers
Statin nonusers	407 (69)	1.00 (ref)	1.00 (ref)
Statin users	243 (24)	0.43 (0.26–0.72)	0.42 (0.25–0.72)
Former smokers
Statin nonusers	585 (109)	1.00 (ref)	1.00 (ref)
Statin users	407 (67)	0.78 (0.56–1.10)	0.84 (0.59–1.19)
Current smokers
Statin nonusers	213 (55)	1.00 (ref)	1.00 (ref)
Statin users	75 (20)	1.04 (0.57–1.90)	1.36 (0.70–2.64)

↵^aAdjusted for age only.
↵^bAdjusted for age, race, site, BMI, cholesterol intake, percent saturated fat intake, and prostate cancer screening frequency.