Serum 25-Hydroxy Vitamin D and Prostate Cancer Risk in a Large Nested Case–Control Study

Demetrius Albanes; Alison M. Mondul; Kai Yu; Dominick Parisi; Ronald L. Horst; Jarmo Virtamo; Stephanie J. Weinstein

doi:10.1158/1055-9965.EPI-11-0403

DOI: 10.1158/1055-9965.EPI-11-0403 Published September 2011

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Figure 1.
Individual serum 25(OH)D concentration plotted by week of blood collection in 1,000 controls in the ATBC Study (1985–2005). Smoothed line represents predicted 25(OH)D values calculated using a locally weighted polynomial regression.
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Figure 2.
Published nested case–control studies of serum 25(OH)D and risk of developing prostate cancer.

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Table 1.

Selected baseline characteristics of prostate cancer cases and controls, the ATBC Study

Characteristic	Median (25%–75%) or %
	Cases (n = 1,000)	Controls (n = 1,000)
Age, y	57.0 (54.0–62.0)	57.0 (54.0–62.0)
Height, cm	174.0 (170.0–178.0)	173.0 (169.0–177.0)
Weight, kg	77.9 (70.9–86.9)	77.3 (70.0–85.3)
BMI, kg/m²	26.0 (23.9–28.5)	25.8 (23.6–28.2)
Cigarettes per day	20.0 (15.0–25.0)	20.0 (15.0–25.0)
Years of smoking	36.5 (30.0–42.0)	37.0 (31.0–42.0)
History of BPH, %	5.2	4.0
History of diabetes, %	2.3	3.8
Family history of prostate cancer,^a %	5.2	2.9^b
Leisure activity, moderate and heavy (%)	60.4	59.1
Vitamin D supplement use, %	7.8	6.5
Calcium supplement use, %	11.6	10.7
Energy intake,^c kcal/d	2,612 (2,178–3,156)	2,636 (2,156–3,090)
Dietary vitamin D intake,^c μg/d	4.7 (3.2–6.8)	4.7 (3.4–6.5)
Dietary calcium intake,^c mg/d	1,335 (1,003–1,725)	1,335 (989–1,708)
Dietary fat intake,^c g/d	118 (96–147)	119 (95–146)
Ethanol consumption,^c g/d	10.7 (2.3–24.3)	9.2 (1.7–22.9)
Serum α-tocopherol, mg/L	11.4 (9.8–13.4)	11.6 (10.1–13.6)^d
Serum retinol, μg/L	589 (513–671)	570 (499–662)^d
Serum β-carotene, μg/L	180 (121–270)	184 (123–286)
Serum total cholesterol, mmol/L	6.21 (5.43–6.93)	6.27 (5.53–7.07)
Serum 25(OH) vitamin D, nmol/L	34.5 (22.7–50.0)	33.6 (21.4–49.1)

Abbreviation: BPH, benign prostatic hyperplasia.

^aFamily history data available for 76% of cases and controls.
^bP ≤ 0.01 by χ² test. All statistical tests are 2-sided.
^cDietary data available for 93% of cases and controls.
^dP ≤ 0.05 by Wilcoxon rank-sum test.

Table 2.

Selected baseline characteristics (medians or percents) of the 1,000 controls by quintile^a of fasting serum 25(OH)D, the ATBC Study

Characteristic	Quintile 1	Quintile 2	Quintile 3	Quintile 4	Quintile 5
Age, y	58.0	57.0	57.0	58.0	58.0
Height, cm	173.0	173.0	173.0	174.0	173.0
Weight, kg	76.1	76.2	77.8	78.8	77.1
BMI, kg/m²	25.7	25.3	26.0	26.1	25.9
Cigarettes per day	20	20	20	20	20
No. of years of smoking	38.0	37.0	36.0	36.0	37.0
History of diabetes, %	2.0	3.5	6.5	2.0	5.0
History of BPH, %	5.0	3.5	4.0	4.5	3.0
Family history of prostate cancer,^b %	2.5	3.0	2.0	5.5	1.5
Leisure activity, moderate and heavy, %	50.8	51.5	64.5	63.5	65.3
Vitamin D supplement use, %	2.5	5.0	6.0	7.5	11.6
Calcium supplement use, %	6.5	8.0	12.5	11.0	15.6
Energy intake,^c kcal/d	2,648	2,829	2,653	2,700	2,504
Dietary vitamin D intake,^c μg/d	3.7	4.4	4.6	5.2	5.9
Dietary calcium intake,^c mg/d	1,446	1,409	1,357	1,404	1,347
Dietary fat intake,^c g/d	119	124	118	124	111
Fruit consumption,^c g/d	100	98	120	124	123
Vegetable consumption,^c g/d	87	94	103	104	117
Ethanol consumption,^c g/d	7.7	6.9	8.6	9.7	11.9
Serum α-tocopherol, mg/L	11.3	11.6	11.5	12.0	11.7
Serum retinol, μg/L	544	552	583	580	592
Serum β-carotene, μg/L	180	186	168	190	192
Serum total cholesterol, mmol/L	6.45	6.32	6.25	6.33	5.98
Serum 25(OH) vitamin D, nmol/L	14.2	22.6	31.2	43.9	63.6

Abbreviation: BPH, benign prostatic hyperplasia.

^aCutoff points for season-specific quintiles were Q1 ≤16.3, Q2 >16.3 and ≤23.8, Q3 >23.8 and ≤33.3, Q4 >33.3 and ≤45.6, Q5 >45.6 nmol/L for the less sunny months; Q1 ≤25.9, Q2 >25.9 and ≤35.7, Q3 >35.7 and ≤48.3, Q4 >48.3 and ≤59.9, Q5 >59.9 nmol/L for sunnier months.
^bFamily history data available for 76% of cases and controls.
^cDietary data available for 93% of cases and controls

Table 3.

Association between serum 25(OH)D categories and risk of prostate cancer, ATBC Study

	Quintiles of 25(OH)D^a					P_trend
	1	2	3	4	5
Season-specific
Cases/controls, n	168/201	201/200	208/199	197/200	225/199
OR^b (95% CI)	1.00 (reference)	1.29 (0.95–1.74)	1.34 (1.00–1.80)	1.26 (0.93–1.72)	1.56 (1.15–2.12)	0.01
Season-adjusted
Cases/controls, n	174/200	198/200	193/199	218/200	216/200
OR^b (95% CI)	1.00 (reference)	1.17 (0.87–1.57)	1.12 (0.84–1.51)	1.34 (0.99–1.82)	1.36 (1.01–1.82)	0.03
	Categories of 25(OH)D, nmol/L
	<25	25 to <37.5	37.5 to <50	50 to <75	≥75
Clinically predefined
Cases/controls, n	299/327	255/241	195/190	194/195	56/46
OR^b (95% CI)	0.81 (0.60–1.08)	0.94 (0.71–1.26)	0.96 (0.71–1.31)	1.00 (reference)	1.16 (0.73–1.86)	0.07

^aCutoff -points for season-specific quintiles were Q1 ≤16.3, Q2 >16.3 and ≤23.8, Q3 >23.8 and ≤33.3, Q4 >33.3 and ≤45.6, Q5 >45.6 nmol/L for the less sunny months; Q1 ≤25.9, Q2 >25.9 and ≤35.7, Q3 >35.7 and ≤48.3, Q4 >48.3 and ≤59.9, Q5: >59.9 nmol/L for sunnier months. Cutoff points for season-adjusted quintiles were Q1 ≤3.00, Q2 >3.00 and ≤3.34, Q3 >3.34 and ≤3.63, Q4 >3.63 and ≤3.92, Q5 >3.92 residual units.
^bORs based on conditional logistic regression. Models conditioned on the matching factors and adjusted for age, family history of prostate cancer, and serum α-tocopherol.

Table 4.

Association between serum 25(OH)D and risk of prostate cancer, stratified by selected baseline and clinical characteristics, the ATBC Study

	Quintiles^a					P_trend
	1	2	3	4	5
Total vitamin D intake (diet + supplements)^b
Low (<5.0 μg/d)
Cases/controls, n	121/137	107/103	88/99	87/82	60/56
OR^c (95% CI)	1.00 (reference)	1.22 (0.84–1.78)	1.04 (0.71–1.54)	1.28 (0.86–1.91)	1.24 (0.79–1.95)	0.30
High (≥5.0 μg/d)
Cases/controls, n	41/52	84/86	108/94	106/112	153/132
OR^c (95% CI)	1.00 (reference)	1.34 (0.80–2.26)	1.65 (1.00–2.75)	1.32 (0.80–2.18)	1.69 (1.04–2.75)	0.08
					P_interaction	0.57
Total calcium intake (diet + supplements)^b
Low (<1,338 mg)
Cases/controls, n	82/80	98/91	102/106	87/98	107/102
OR^c (95% CI)	1.00 (reference)	1.09 (0.71–1.67)	0.99 (0.65–1.51)	0.93 (0.60–1.43)	1.15 (0.75–1.75)	0.77
High (≥1,338 mg)
Cases/controls, n	80/109	93/98	94/87	106/96	106/86
OR^c (95% CI)	1.00 (reference)	1.40 (0.92–2.12)	1.65 (1.08–2.52)	1.60 (1.06–2.42)	1.82 (1.20–2.76)	0.01
					P_interaction	0.06
Leisure activity
Sedentary
Cases/controls, n	94/99	100/97	82/71	54/73	65/69
OR^c (95% CI)	1.00 (reference)	1.21 (0.80–1.82)	1.35 (0.87–2.10)	0.79 (0.50–1.27)	1.12 (0.71–1.78)	0.81
Moderate/heavy
Cases/controls, n	74/102	101/103	126/129	143/127	160/130
OR^c (95% CI)	1.00 (reference)	1.42 (0.94–2.15)	1.44 (0.97–2.14)	1.67 (1.13–2.46)	1.85 (1.26–2.72)	0.002
					P_interaction	0.03
Season of blood collection
Less sunny months (November–April)
Cases/controls, n	120/98	120/115	119/131	120/130	119/125
OR^d (95% CI)	1.00 (reference)	1.24 (0.83–1.86)	1.42 (0.96–2.10)	1.46 (0.97–2.21)	1.42 (0.95–2.12)	0.07
Sunnier months (May–October)
Cases/controls, n	81/70	80/86	81/77	80/67	80/100
OR^d (95% CI)	1.00 (reference)	1.20 (0.72–1.98)	1.18 (0.72–1.94)	1.01 (0.60–1.69)	1.70 (1.01–2.85)	0.12
					P_interaction	0.78
Vitamin E supplementation
No
Cases/controls, n	90/94	112/100	116/95	91/100	118/108
OR^c (95% CI)	1.00 (reference)	1.29 (0.86–1.94)	1.49 (0.99–2.24)	1.05 (0.69–1.59)	1.29 (0.86–1.93)	0.56
Yes
Cases/controls, n	78/107	89/100	92/105	106/100	107/91
OR^c (95% CI)	1.00 (reference)	1.29 (0.85–1.95)	1.23 (0.82–1.86)	1.54 (1.02–2.32)	1.74 (1.15–2.64)	0.006
					P_interaction	0.12
Serum α-tocopherol
Low (<11.6 mg/L)
Cases/controls, n	104/107	111/103	114/104	91/89	105/98
OR^c (95% CI)	1.00 (reference)	1.19 (0.80–1.76)	1.25 (0.84–1.85)	1.17 (0.78–1.77)	1.23 (0.82–1.84)	0.38
High (≥11.6 mg/L)
Cases/controls, n	64/94	90/97	94/96	106/111	120/101
OR^c (95% CI)	1.00 (reference)	1.51 (0.97–2.34)	1.63 (1.05–2.52)	1.45 (0.95–2.23)	2.00 (1.30–3.07)	0.01
					P_interaction	0.15
Serum retinol
Low (<570 μg/L)
Cases/controls, n	81/120	95/112	91/93	81/93	93/83
OR^c (95% CI)	1.00 (reference)	1.39 (0.93–2.09)	1.67 (1.10–2.54)	1.43 (0.93–2.19)	1.80 (1.18–2.75)	0.01
High (≥570 μg/L)
Cases/controls, n	87/81	106/88	117/107	116/107	132/116
OR^c (95% CI)	1.00 (reference)	1.19 (0.78–1.81)	1.10 (0.73–1.65)	1.09 (0.72–1.64)	1.22 (0.81–1.82)	0.51
					P_interaction	0.22
Serum total cholesterol
Low (<6.27 mmol/L)
Cases/controls, n	95/91	105/97	112/100	99/97	124/116
OR^c (95% CI)	1.00 (reference)	1.08 (0.72–1.62)	1.14 (0.76–1.70)	1.03 (0.69–1.56)	1.12 (0.75–1.66)	0.69
High (≥6.27 mmol/L)
Cases/controls, n	73/110	96/103	96/100	98/103	101/83
OR^c (95% CI)	1.00 (reference)	1.53 (1.01–2.32)	1.61 (1.06–2.45)	1.56 (1.03–2.38)	2.09 (1.36–3.21)	0.003
					P_interaction	0.07
Case stage/Gleason score^e
Nonaggressive
Cases/controls, n	57/61	77/88	80/68	78/86	52/81
OR^d (95% CI)	1.00 (reference)	0.99 (0.59–1.65)	1.34 (0.81–2.23)	1.00 (0.60–1.66)	1.31 (0.81–2.13)	0.29
Aggressive
Cases/controls, n	84/103	81/79	84/85	82/71	90/84
OR^d (95% CI)	1.00 (reference)	1.28 (0.82–2.01)	1.34 (0.85–2.09)	1.59 (0.98–2.60)	1.70 (1.05–2.76)	0.02
					P_interaction	0.43
Follow-up period
<10 y
Cases/controls, n	61/75	65/62	67/57	64/66	65/63
OR^d (95% CI)	1.00 (reference)	1.16 (0.69–1.96)	1.42 (0.84–2.39)	1.06 (0.60–1.88)	1.51 (0.86–2.63)	0.21
≥10 y
Cases/controls, n	107/126	136/138	141/143	133/134	160/136
OR^d (95% CI)	1.00 (reference)	1.27 (0.88–1.85)	1.30 (0.90–1.88)	1.30 (0.89–1.89)	1.59 (1.09–2.31)	0.03
					P_interaction	0.67

^aCutoff points for season-specific quintiles were Q1 ≤16.3, Q2 >16.3 and ≤23.8, Q3 >23.8 and ≤33.3, Q4 >33.3 and ≤45.6, Q5 >45.6 nmol/L for the less sunny months; Q1 ≤25.9, Q2 >25.9 and ≤35.7, Q3 >35.7 and ≤48.3, Q4 >48.3 and ≤59.9, Q5 >59.9 nmol/L for sunnier months.
^bDietary data available for 1,909 subjects.
^cORs based on unconditional logistic regression, adjusted for age, season of blood draw, family history of prostate cancer, and serum α-tocopherol.
^dORs based on conditional logistic regression, conditioned on the matching factors and adjusted for age, family history of prostate cancer, and serum α-tocopherol.
^eData for disease stage and Gleason score were available for 636 cases.