Serum 25-hydroxyvitamin D levels predict cancer survival: a prospective cohort with measurements prior to and at the time of cancer diagnosis

Figures & data

Table 1 Characteristics of the cancer patients; numbers (n), percentage (%), median, range, and means

Characteristics	Cancer site				Total
	Breast	Colon	Lung	Lymphoma
Cases/cancer deaths, n	202/68	37/22	193/168	124/55	556/313
Sex, cases/cancer deaths, n
Men	0	23/15	122/105	79/35	224/155
Women	202/68	14/7	71/63	45/20	332/158
Age at diagnosis
Years, median (range)	55 (34–75)	58 (32–75)	59 (39–82)	57 (39–79)	57 (32–82)
Time between prediagnostic serum sampling and diagnosis
Years, median (range)	11.7 (1.1–28.9)	13.5 (3.0–22.1)	17.7 (2.3–34.4)	15.2 (2.9–31.8)	14.4 (1.1–34.4)
Prediagnostic 25-OHD, nmol/L, median (range)	62.5 (18.0–119.0)	61.0 (24.0–129.0)	64.5 (17.4–132.4)	64.4 (32.3–142.5)	63.3 (17.4–142.5)
1 [<46 nmol/L], mean (n)	36.3 (44)	36.0 (7)	37.7 (41)	40.1 (22)	37.5 (114)
2 [46–61 nmol/L], mean (n)	53.9 (56)	55.1 (14)	54.7 (50)	54.7 (34)	54.5 (154)
3 [62–81 nmol/L], mean (n)	71.4 (65)	72.6 (10)	71.9 (58)	70.5 (35)	71.4 (168)
4 [≥82 nmol/L], mean (n)	94.3 (37)	101.3 (6)	97.4 (44)	97.7 (33)	96.7 (120)
Season-standardized prediagnostic 25-OHD nmol/L, median (range)	61.4 (20.9–139.5)	60.7 (25.9–111.6)	64.0 (18.2–151.7)	66.5 (34.8–128.7)	63.2 (18.2–151–7)
Diagnostic 25-OHD, nmol/L, median (range)	72.0 (13.0–177.0)	62.0 (24.0–124.0)	55.0 (15.0–184.0)	59.5 (16.0–185.0)	62.5 (13.0–185.0)
1 [<46 nmol/L], mean (n)	34.7 (29)	38.0 (10)	34.8 (60)	35.9 (39)	35.3 (138)
2 [46–61 nmol/L], mean (n)	54.0 (47)	50.0 (8)	52.7 (55)	54.1(26)	53.3 (136)
3 [62–81 nmol/L], mean (n)	71.5 (48)	71.8 (13)	71.4 (40)	70.2 (33)	71.2 (134)
4 [≥82 nmol/L], mean (n)	99.6 (78)	97.2 (6)	98.1 (38)	103.6 (26)	99.8 (148)
Season-standardized diagnostic 25-OHD nmol/L, median (range)	74.2 (13.6–151.9)	63.9 (26.9–157.6)	56.6 (15.7–152.7)	59.3 (16.8–180.6)	63.5 (13.6–180.6)

Table 2 Hazard ratios (HR) with 95% confidence interval (95% CI) of cancer case fatality according to predefined categories of prediagnostic (I) and diagnostic (II) 25-OHD levels, from crude and adjusted analyses

	n^a	Crude model	Adjusted model^b
		HR (95% CI)	HR (95% CI)
I. Prediagnostic 25-OHD^c
1 [<46 nmol/L]	114/73	1.00 reference	1.00 reference
2 [46–61 nmol/L]	154/76	0.62 (0.45–0.85)	0.52 (0.37–0.72)
3 [62–81 nmol/L]	168/102	0.75 (0.56–1.02)	0.61 (0.44–0.84)
4 [≥82 nmol/L]	120/62	0.64 (0.46–0.91)	0.46 (0.32–0.66)
p for trend		0.066	0.001
II. Diagnostic 25-OHD^c
1 [<46 nmol/L]	138/97	1.00 reference	1.00 reference
2 [46–61 nmol/L]	136/83	0.61 (0.46–0.82)	0.74 (0.55–0.99)
3 [62–81 nmol/L]	134/64	0.41 (0.30–0.56)	0.44 (0.32–0.61)
4 [≥82 nmol/L]	148/69	0.36 (0.27–0.50)	0.41 (0.30–0.57)
p for trend		<0.001	<0.001

Notes: ^aNumber of cases/cancer deaths; ^bAdjusted for sex, age at diagnosis, season of serum sampling, and serum storage time; ^cThe two serum samples were collected in average 14.4 years apart.

Table 3 Hazard ratios (HR) with 95% confidence interval (95% CI) of cancer case fatality by cancer site, according to predefined cancer-specific categories of prediagnostic (I) and diagnostic (II) 25-OHD serum levels. The two serum samples were collected in average 14.4 years apart

	Cancer site
	Breast HR (95% CI)^a	Colon HR (95% CI)^a	Lung HR (95% CI)^a	Lymphoma HR (95% CI)^a
n^b	202/68	37/22	193/168	124/55
I. Prediagnostic 25-OHD^c
1	1.00	1.00	1.00	1.00
2	0.66 (0.36–1.21)	0.24 (0.04–1.49)	1.08 (0.63–1.86)	0.40 (0.15–1.09)
3	0.66 (0.35–1.25)	0.28 (0.06–1.31)	0.74 (0.45–1.23)	1.05 (0.44–2.50)
4	0.39 (0.14–1.06)	0.61 (0.13–2.91)	0.55 (0.31–0.96)	0.29 (0.10–0.82)
p for trend	0.055	0.925	0.004	0.184
II. Diagnostic 25-OHD^c
1	1.00	1.00	1.00	1.00
2	0.40 (0.19–0.81)	1.15 (0.30–4.43)	0.52 (0.34–0.81)	0.91 (0.45–1.86)
3	0.44 (0.22–0.87)	0.53 (0.14–1.97)	0.48 (0.31–0.75)	0.38 (0.17–0.88)
4	0.32 (0.15–0.67)	0.18 (0.03–0.98)	0.30 (0.19–0.47)	0.36 (0.16–0.81)
p for trend	0.008	0.033	<0.001	0.003

Notes: ^aAdjusted for sex, age at diagnosis, season of serum sampling, and serum storage time; ^bNumber of case/deaths due to cancer; ^cCancer-specific category limits of 25-OHD (nmol/L): breast ≤50, 51–67, 68–86, >86; colon ≤44, 45–56, 57–77,>77; lung ≤41, 42–56, 57–76,>76; lymphoma ≤44, 45–60, 61–77,>77.

Table 4 Hazard ratios (HR) with 95% confidence intervals (95% CI) of cancer case fatality by all possible combinations of season-standardized 25-OHD categories in prediagnostic and diagnostic samples

25-OHD level		n^b	HR (95% CI)^c
Prediagnostic sample^a	Diagnostic sample^a
Low (<46 nmol/L)	Low (<46 nmol/L)	50/32	1.00 reference
Low (<46 nmol/L)	Intermediate (46–61 nmol/L)	23/15	0.84 (0.46–1.56)
Low (<46 nmol/L)	High (≥62 nmol/L)	23/11	0.53 (0.27–1.05)
Intermediate (46–61 nmol/L)	Low (<46 nmol/L)	47/30	0.86 (0.52–1.42)
Intermediate (46–61 nmol/L)	Intermediate (46–61 nmol/L)	51/34	0.87 (0.54–1.41)
Intermediate (46–61 nmol/L)	High (≥62 nmol/L)	59/26	0.43 (0.26–0.73)
High (≥62 nmol/L)	Low (<46 nmol/L)	37/30	1.01 (0.61–1.69)
High (≥62 nmol/L)	Intermediate (46–61 nmol/L)	55/36	0.70 (0.43–1.14)
High (≥62 nmol/L)	High (≥62 nmol/L)	211/99	0.41 (0.27–0.61)
p for trend			<0.001

Notes: ^aThe two serum samples were collected in average 14.4 years apart; ^bNumber of cases/cancer deaths; ^cAdjusted for sex, age at diagnosis, and serum storage time.

Table 5 Hazard ratios (HR) with 95% confidence interval (95% CI) of cancer case fatality by tertiles (T) of change in season-standardized 25-OHD between prediagnostic and diagnostic samples, overall (I), and according to time-span between collection of the samples; <10 years (II) and ≥10 years (III)

25-OHD change^a	n^b	HR (95% CI)^c
I. Overall
T1 (loss)	186/126	1.00 (reference)
T2 (stable)	185/100	0.76 (0.58–0.99)
T3 (rise)	185/87	0.57 (0.43–0.75)
p for trend		<0.001
II. <10 years
T1 (loss)	17/32	1.00 (reference)
T2 (stable)	17/36	0.94 (0.47–1.87)
T3 (rise)	22/50	0.89 (0.46–1.70)
Trend		0.718
III. ≥10 years
T1 (loss)	110/154	1.00 (reference)
T2 (stable)	82/149	0.70 (0.52–0.93)
T3 (rise)	65/135	0.50 (0.37–0.69)
p for trend		<0.001

Notes: ^aTertile 1 (loss) −86.8 to −26.4; Tertile 2 (stable) −10.4 to +0.14; Tertile 3 (rise) +9.6 to +27.3; ^bNumber of cases/cancer deaths; ^cAdjusted for sex and age at diagnosis.

Table S1 Hazard ratios (HR) with 95% confidence interval (95% CI) of cancer case fatality according to clinically categories of pre-diagnostic (I) and diagnostic (II) 25-OHD levels

	n^a	Crude model	Adjusted model^b
HR (95% CI)	HR (95% CI)
I. Pre-diagnostic 25-OHD^c
Insufficient [<50 nmol/L]	142/85	1.00 reference	1.00 reference
Sufficient [50–75 nmol/L]	235/131	0.78 (0.59-1.02)	0.68 (0.52–0.91)
Optimal [>75 nmol/L]	179/97	0.74 (0.46–0.91)	0.59 (0.43–0.81)
p for trend		0.052	0.001
II. Diagnostic 25-OHD^c
Insufficient [<50 nmol/L]	171/122	1.00 reference	1.00 reference
Sufficient [50–75 nmol/L]	189/96	0.47 (0.36–0.61)	0.51 (0.39–0.67)
Optimal [>75 nmol/L]	196/95	0.40 (0.31–0.53)	0.44 (0.33–0.58)
p for trend		<0.001	<0.001

Notes: ^aNumber of cases/cancer deaths; ^bAdjusted for sex, age at diagnosis, season of serum sampling, and serum storage time; ^cThe two serum samples were collected in average 14.4 years apart.

Table S2 Hazard ratios (HR) with 95% confidence interval (95% CI) of cancer case fatality according to season-standardized 25-OHD levels in predefined categories of pre-diagnostic (I) and diagnostic (II) 25-OHD levels

	n^a	Crude model	Adjusted model^b
		HR (95% CI)	HR (95% CI)
I. Pre-diagnostic 25-OHD^c
1 [<46 nmol/L]	96/58	1.00 reference	1.00 reference
2 [46–61 nmol/L]	169/94	0.85 (0.61–1.18)	0.77 (0.56–1.08)
3 [62–81 nmol/L]	181/100	0.74 (0.53–1.02)	0.63 (0.44–0.91)
4 [≥82 nmol/L]	110/61	0.78 (0.54–1.12)	0.63 (0.44–0.91)
p for trend		0.113	0.007
II. Diagnostic 25-OHD^c
1 [<46 nmol/L]	134/92	1.00 reference	1.00 reference
2 [46–61 nmol/L]	136/89	0.70 (0.52–0.93)	0.79 (0.59–1.06)
3 [62–81 nmol/L]	147/69	0.42 (0.31–0.57)	0.47 (0.34–0.64)
4 [≥82 nmol/L]	139/63	0.36 (0.26–0.50)	0.41 (0.30–0.58)
p for trend		<0.001	<0.001

Notes: ^aNumber of cases/cancer deaths; ^bAdjusted for sex, age at diagnosis, season of serum sampling, and serum storage time; ^cThe two serum samples were collected in average 14.4 years apart.