Prediagnostic Toenail Selenium and Risk of Bladder Cancer

Maurice P. A. Zeegers; R. Alexandra Goldbohm; Peter Bode; Piet. A. van den Brandt

DOI: Published November 2002

Article Figures & Data

Tables

Table 1

Toenail selenium levels (μg/g) in bladder cancer cases according to sex and time between baseline and bladder cancer diagnosis; Netherlands Cohort Study (1986–1992)

Cases^a	No. of subjects	Toenail selenium level (μg/g)
Cases^a	No. of subjects			Mean	SD	P^b
Sex
Men	372	0.536	0.215	Reference
Women	59	0.568	0.122	0.02
Year of follow-up^c
1	47	0.518	0.091	0.04
2	61	0.523	0.263	0.21
3	74	0.546	0.128	0.50
4	75	0.544	0.155	0.90
5	70	0.568	0.154	0.63
6	84	0.590	0.721	Reference
7	20	0.595	0.123	Reference

^a Mean ± SD selenium levels in subcohort members were 0.547 ± 0.126 μg/g for men (n = 1211) and 0.575 ± 0.109 μg/g for women (n = 1248).
^b Partial t tests between strata and reference group, based on In-transformed toenail selenium levels.
^c Presented results per year of follow-up were adjusted for sex through linear regression analysis.

Table 2

Incidence RR of bladder cancer according to toenail selenium levels; Netherlands Cohort Study (1986–1992)

Quintiles of toenail selenium (boundaries in μg/g)	All years of follow-up
Quintiles of toenail selenium (boundaries in μg/g)		Cases in cohort	Person years in subcohort	RR (95% CI)^a	RR (95% CI)^b	RR (95% CI)^b
1 (≤0.483)	114	2986	1.00 (reference)	1.00 (reference)	1.00 (reference)
2 (0.483 to ≤0.530)	116	3022	1.05 (0.79–1.40)	1.09 (0.80–1.48)	1.19 (0.86–1.64)
3 (0.530 to ≤0.573)	78	3031	0.51 (0.36–0.73)	0.55 (0.38–0.79)	0.61 (0.42–0.89)
4 (0.573 to ≤0.630)	62	2993	0.53 (0.37–0.76)	0.63 (0.43–0.91)	0.63 (0.42–0.94)
5 (>0.630)	61	3001	0.54 (0.38–0.76)	0.67 (0.46–0.97)	0.78 (0.54–1.14)
P for linear trend			<0.01	<0.01	<0.01
Increment in standard units^c			0.86 (0.77–0.96)	0.94 (0.83–1.05)	0.89 (0.79–1.00)

^a Adjusted for age (years) and sex.
^b Adjusted for age, sex, number of cigarettes/day, and years of cigarette smoking.
^c z-scores based on In-transformed toenail selenium levels (increment of 0.202 μg/g).

Table 3

Incidence RR of bladder cancer according to toenail selenium levels and smoking status; Netherlands Cohort Study (1986–1992)

Smoking status and cessation^a	No. of cases	Quintile of toenail selenium (boundaries in μg/g)							P trend
Smoking status and cessation^a	No. of cases			1 (≤0.483)	2 (≤0.530)	3 (≤0.573)	4 (≤0.630)	5 (>0.630)	P trend
Never^b	51	1.00 (reference)	2.69 (1.02–7.09)	1.37 (0.50–3.79)	1.09 (0.38–3.14)	1.36 (0.50–3.69)	0.62
Ex^c	186	1.00 (reference)	0.74 (0.46–1.19)	0.48 (0.28–0.81)	0.49 (0.29–0.83)	0.44 (0.26–0.75)	<0.01
≤10 yrs	89	1.00 (reference)	0.42 (0.19–0.94)	0.47 (0.21–1.08)	0.45 (0.20–1.01)	0.30 (0.12–0.75)	<0.01
>10 yrs	96	1.00 (reference)	1.06 (0.55–2.06)	0.48 (0.22–1.01)	0.47 (0.20–1.09)	0.58 (0.29–1.18)	<0.01
Current^c	170	1.00 (reference)	1.36 (0.86–2.14)	0.45 (0.24–0.86)	0.76 (0.39–1.47)	1.13 (0.56–2.27)	0.25

^a P for interaction was 0.19.
^b Adjusted for age (years) and sex.
^c Adjusted for age (years), sex, number of cigarettes/day, and years of cigarette smoking.

Table 4

Incidence RR^a of bladder cancer according to toenail selenium levels by category of vitamin intake; Netherlands Cohort Study (1986–1992)

Group	No. of cases	Quintile of toenail selenium (boundaries in μg/g)							P-trend
Group	No. of cases			1 (≤0.483)	2 (≤0.530)	3 (≤0.573)	4 (0.630)	5 (>0.630)	P-trend
β-Carotene intake^b
Low	167	1.00 (reference)	0.98 (0.59–1.62)	0.50 (0.28–0.89)	0.71 (0.40–1.26)	0.65 (0.36–1.16)	0.02
High	155	1.00 (reference)	1.08 (0.65–1.80)	0.97 (0.55–1.71)	0.66 (0.34–1.26)	0.74 (0.41–1.34)	0.09
Vitamin C intake^b
Low	181	1.00 (reference)	0.95 (0.59–1.53)	0.45 (0.26–0.78)	0.72 (0.41–1.26)	0.77 (0.43–1.37)	0.05
High	140	1.00 (reference)	1.09 (0.64–1.85)	1.01 (0.57–1.80)	0.50 (0.25–1.00)	0.75 (0.41–1.37)	0.06
Vitamin E intake^b
Low	145	1.00 (reference)	1.37 (0.81–2.33)	0.58 (0.30–1.09)	0.76 (0.41–1.42)	0.82 (0.45–1.50)	0.07
High	170	1.00 (reference)	1.09 (0.68–1.75)	0.59 (0.34–1.03)	0.70 (0.38–1.28)	0.73 (0.41–1.29)	0.04

^a Adjusted for age (years), sex, number of cigarettes/day, and years of cigarette smoking.
^b Low and high are defined as the two lowest quintiles and the two highest quintiles of intake, respectively. For β-carotene, the cutoff values for low and high were: ≤2.36, >2.97 mg/day; for vitamin C the corresponding values were ≤86.60 and >107.71 mg/day, and for vitamin E the corresponding values were ≤10.72 and <13.89 mg/day. The Ps for interaction were 0.58, 0.16, and 0.96 for β-carotene, vitamin C, and vitamin E.

Table 5

Incidence RRs for transitional cell carcinoma of the urinary bladder according to toenail selenium levels, with respect to tumor invasiveness and morphology; Netherlands Cohort Study 1986–1992

Quintiles of toenail selenium (boundaries in μg/g)	Noninvasive (T_IS/T_a/T₁)			Invasive (T_2–4)
		Non-papillary^a (n = 16)	Papillary^b (n = 180)	Non-papillary^a (n = 81)	Papillary^b (n = 108)
		RR (95% CI)^c	RR (95% CI)^c	RR (95% CI)^c	RR (95% CI)^c
1 (≤0.483)	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
2 (0.483 to ≤0.530)	1.24 (0.31–4.88)	1.23 (0.80–1.88)	1.11 (0.63–1.95)	0.96 (0.58–1.59)
3 (0.530 to ≤0.573)	1.07 (0.25–4.58)	0.63 (0.37–1.05)	0.45 (0.21–0.96)	0.44 (0.23–0.84)
4 (0.573 to ≤0.630)	1.28 (0.26–6.42)	0.78 (0.46–1.31)	0.17 (0.05–0.57)	0.64 (0.34–1.20)
5 (>0.6300)	0.83 (0.13–5.20)	0.91 (0.55–1.50)	0.62 (0.30–1.28)	0.36 (0.17–0.75)
P for linear trend	0.92	0.18	<0.01	<0.01
Increment in standard units^d	1.08 (0.74–1.58)	1.06 (0.87–1.29)	0.84 (0.69–1.02)	0.82 (0.72–0.94)

^a ICD-O:M8120.
^b ICDO:M8130.
^c Adjusted for age, sex, number of cigarettes smoked/day, and years of cigarette smoking.
^d z-scores based on In-transformed toenail selenium levels (increment of 0.202 μg/g).

Table 6

Prospective studies of selenium in relation to urinary tract cancer incidence

Study	Country	Sex	Cases	Mean selenium level (cases/controls)	Exposure	Comparison	Site	RR (95% CI)
Nomura et al., 1987 (13)	US	Men	29	12.11/12.49 μg/dl	Serum	Highest vs. lowest quintile	Bladder	0.32
Helzlsouer et al., 1989 (7)	US	Both	35	11.1/11.7 μg/dl	Serum	Highest vs. lowest tertile	Bladder	0.49 (0.16–1.49)
Knekt et al., 1990 (8)	Finland	Men	26	6.16/6.53 μg/dl	Serum	Four higher vs. lowest quintile	Urinary tract	0.34 (0.06–2.06)
Knekt et al., 1990 (8)	Finland	Women	9	7.64/6.67 μg/dl	Serum	Four higher vs. lowest quintile	Urinary tract	2.51 (0.13–47.9)
Garland et al., 1995 (12)	US	Women	28	0.826/0.812 μg/g	Toenail	Mean differences	Urinary tract	P = 0.58^a
Present study	Netherlands	Both	431	0.540/0.561 μg/g	Toenail	Highest vs. lowest quintile	Urinary tract	0.67 (0.46–0.97)