Evaluation of statin use and renal cell carcinoma risk identifies sex-specific associations with RCC subtypes

Figures & data

Figure 1. Statin exposure categorizations evaluated in the study analyses.

Table 1. Age-adjusted characteristics of the study populations by ever statin use in 2000 (HPFS, NHS) and 1999 (NHS II).

	NHS		NHS II		HPFS
	Never users	Ever users	Never users	Ever users	Never users	Ever users
	N = 71,626	N = 21,980	N = 88,714	N = 2713	N = 28,517	N = 9584
Mean age (SD), years*	66 (7.2)	68 (6.7)	45 (4.6)	47 (4.0)	67 (9.4)	68 (8.7)
White race, %	94	94	97	96	96	96
Diabetes mellitus, %	7.6	17	1.7	10	5.6	11
Hypertension, %	46	66	14	41	39	56
Smoking status
Never smokers, %	45	42	66	64	51	45
Past smokers, %	45	48	25	24	44	51
Current smokers, %	9.9	9.7	9.1	12	5.1	4.1
Mean Pack-years of smoking (SD)**	25 (22)	26 (22)	13 (11)	17 (12)	23 (19)	25 (19)
Mean physical activity (SD), MET-h/week	17 (22)	15 (21)	19 (24)	15 (19)	27 (29)	25 (27)
Mean BMI (SD), kg/m^2	27 (5.4)	28 (5.4)	27 (6.2)	30 (6.7)	26 (3.8)	27 (3.7)
BMI categories
≤24.9 kg/m^2, %	46	32	52	25	43	34
25-29.9 kg/m^2, %	33	38	26	31	45	51
≥30 kg/m^2, %	22	30	22	44	12	15
NSAIDs use ≥5 years, %	32	39	36	49	13	17
Mean parity (SD)***	3.2 (1.5)	3.1 (1.5)	1.9 (1.2)	1.7 (1.2)	–	–
Nulliparous, %	7.3	7.0	18	22	–	–

Abbreviations. BMI: body mass index; HPFS: Health Professionals Follow-up Study; MET: metabolic equivalent of task; NHS: Nurses’ Health Study; NHS II: Nurses’ Health Study; NSAIDs: non-steroidal anti-inflammatory drugs; SD: standard deviation.

* Not age standardized.

** Among ever smokers

*** Among parous women.

Table 2. Hazard ratios, and 95% confidence intervals for renal cell carcinoma (RCC) risk according to statin use in the HPFS (1990–2016), NHS (1994–2016), NHS II (1999–2015) cohorts.

	Never users (reference)	Ever users
		All ever users	Total duration <4 years	Total duration ≥4 years
Total RCC
NHS, N	194	116	43	73
MV-adjusted HR	1.00 (ref)	0.92 (0.71–1.19)	0.99 (0.70–1.39)	0.88 (0.65–1.19)
NHS II, N	69	27	7	20
MV-adjusted HR	1.00 (ref)	0.91 (0.54–1.52)	0.63 (0.28–1.40)	1.13 (0.62–2.04)
HPFS, N	163	92	26	66
MV-adjusted HR	1.00 (ref)	1.06 (0.79–1.42)	0.87 (0.56–1.34)	1.18 (0.84–1.65)
Combined HR	1.00 (ref)	0.97 (0.81–1.16)	0.90 (0.70–1.16)	1.02 (0.82–1.26)
Fatal RCC*
NHS, N	52	17	5	12
MV-adjusted HR	1.00 (ref)	0.80 (0.44–1.45)	0.56 (0.22–1.42)	1.01 (0.50–2.02)
HPFS, N	51	16	8	8
MV-adjusted HR	1.00 (ref)	0.79 (0.41–1.54)	1.08 (0.48–2.39)	0.59 (0.25–1.41)
Combined HR	1.00 (ref)	0.79 (0.51–1.23)	0.81 (0.42–1.54)	0.81 (0.47–1.40)
Advanced stage**
NHS, N	57	29	9	20
MV-adjusted HR	1.00 (ref)	0.92 (0.56–1.52)	0.74 (0.35–1.53)	1.07 (0.60–1.91)
NHS II, N	21	5	0	5
MV-adjusted HR	1.00 (ref)	0.63 (0.22–1.83)	–	1.08 (0.36–3.22)
HPFS, N	57	22	1	21
MV-adjusted HR	1.00 (ref)	0.84 (0.47–1.48)	0.53 (0.21–1.36)	1.06 (0.55–2.03)
Combined HR	1.00 (ref)	0.85 (0.60–1.21)	0.65 (0.36–1.16)	1.06 (0.71–1.59)
Localized stage**
NHS, N	127	78	30	48
MV-adjusted HR	1.00 (ref)	0.87 (0.64–1.20)	1.03 (0.68–1.56)	0.78 (0.54–1.14)
NHS II, N	44	18	7	11
MV-adjusted HR	1.00 (ref)	1.03 (0.54–1.96)	0.98 (0.42–2.28)	1.07 (0.49–2.36)
HPFS, N	95	66	8	58
MV-adjusted HR	1.00 (ref)	1.18 (0.82–1.68)	0.94 (0.56–1.59)	1.33 (0.89–1.98)
Combined HR	1.00 (ref)	1.00 (0.80–1.25)	0.99 (0.73–1.34)	1.02 (0.70–1.48)
High grade**
NHS, N	41	43	19	24
MV-adjusted HR	1.00 (ref)	1.75 (1.07–2.85)	2.18 (1.23–3.85)	1.44 (0.81–2.57)
NHS II, N	21	5	2	3
MV-adjusted HR	1.00 (ref)	0.66 (0.22–1.99)	0.65 (0.14–2.98)	0.66 (0.17–2.58)
HPFS, N	42	29	3	26
MV-adjusted HR	1.00 (ref)	1.19 (0.69–2.06)	0.71 (0.29–1.72)	1.53 (0.84–2.81)
Combined HR	1.00 (ref)	1.32 (0.86–2.02)	1.15 (0.49–2.75)	1.38 (0.93–2.06)
Low grade**
NHS, N	116	57	19	38
MV-adjusted HR	1.00 (ref)	0.67 (0.47–0.95)	0.70 (0.42–1.14)	0.66 (0.44–0.99)
NHS II, N	43	17	4	13
MV-adjusted HR	1.00 (ref)	0.82 (0.43–1.59)	0.52 (0.18–1.50)	1.07 (0.51–2.26)
HPFS, N	72	43	6	37
MV-adjusted HR	1.00 (ref)	1.03 (0.67–1.58)	0.75 (0.39–1.45)	1.21 (0.75–1.96)
Combined HR	1.00 (ref)	0.81 (0.61–1.06)	0.69 (0.47–1.00)	0.91 (0.60–1.40)
Clear cell RCC
NHS, N	144	77	27	50
MV-adjusted HR	1.00 (ref)	0.77 (0.56–1.04)	0.80 (0.53–1.23)	0.74 (0.52–1.07)
NHS II, N	54	16	3	13
MV-adjusted HR	1.00 (ref)	0.59 (0.31–1.12)	0.31 (0.09–1.01)	0.80 (0.39–1.65)
HPFS, N	101	66	8	58
MV-adjusted HR	1.00 (ref)	1.38 (0.97–1.98)	1.01 (0.59–1.72)	1.65 (1.10–2.47)
Combined HR	1.00 (ref)	0.89 (0.55–1.44)^†	0.78 (0.50–1.22)	1.01 (0.57–1.80)^†

Abbreviations. HPFS: Health Professionals Follow-up Study; HR: hazard ratio; MV: multivariable; NHS: Nurses’ Health Study; NHS II: Nurses’ Health Study.

* In the NHS II, there were insufficient fatal RCC cases before the end of the follow-up period for meaningful analysis.

** Advanced stage ≥ pT3, N1, or M1; Localized stage < pT3 with N0 and M0; High-grade – Fuhrman grade 3 or 4 or poorly or undifferentiated cancer; Low grade – Fuhrman grade 1 or 2 or well or moderately differentiated cancer.

^† These combined HRs showed statistically significant heterogeneity across cohorts (p-heterogeneity = 0.02 for ever vs. never users, and 0.01 for ≥4 years users vs. never users).

All MV-adjusted models were adjusted for: age, body mass index, diabetes, hypertension, smoking, physical activity, long-term non-steroidal anti-inflammatory drug use, and parity (NHS and NHS II only).