Circulating vitamin D concentration and risk of prostate cancer: a dose–response meta-analysis of prospective studies

Figures & data

Figure 1 Selection of studies for inclusion in meta-analysis.

Table 1 Characteristics of included studies on the association between circulating vitamin D concentrations and prostate cancer

References	Design	Country	Participants	Time of follow-up or from blood collection to diagnosis	Quality (NOS score)
Braun et al (1995)^Citation20	Nested case–control	USA	61 prostate cancer cases and 122 matched controls	14 years	High (6)
Nomura et al (1998)^Citation21	Nested case–control	USA	136 cases of prostate cancer and 136 matched controls	23 years	High (7)
Tuohimaa et al (2004)^Citation69	Nested case–control	Norway, Finland, and Sweden	622 prostate cancer cases and 1,451 matched controls	10 years	High (7)
Platz et al (2004)^Citation66	Nested case–control	USA	460 prostate cancer cases and 460 matched controls	2.2 years	High (9)
Jacobs et al (2004)^Citation64	Nested case–control	USA	83 prostate cancer cases and 166 matched controls	5.2 years	High (8)
Baron et al (2005)^Citation22	Prospective cohort	USA	672 men and 70 incident prostate cancer cases	10.3 years	High (8)
Faupel-Badger et al (2007)^Citation63	Nested case–control	Finland	296 prostate cancer cases and 297 matched controls	9.26 years	High (8)
Ahn et al (2008)^Citation62	Nested case–control	USA	749 case patients with incident prostate cancer and 781 matched control subjects	8 years	High (9)
Travis et al (2009)^Citation68	Nested case–control	Europe	652 prostate cancer cases matched to 752 controls	4.1 years	High (8)
Park et al (2010)^Citation65	Nested case–control	USA	329 prostate cancer cases and 656 matched controls	Not reported	High (7)
Barnett et al (2010)^Citation23	Prospective cohort	USA	5,995 men and 297 incident prostate cancer cases	5.3 years	High (7)
Albanes et al (2011)^Citation30	Nested case–control	Finland	1,000 prostate cancer cases matched to 1,000 controls	20 years	High (9)
Brandstedt et al (2012)^Citation24	Nested case–control	Sweden	943 prostate cancer cases and 943 matched controls	7.6 years	High (7)
Shui et al (2012)^Citation67	Nested case–control	USA	1,260 prostate cancer cases matched to 1,331 matched controls	5.2 years	High (9)
Meyer et al (2013)^Citation25	Nested case–control	Norway	2,106 prostate cancer cases matched to 2,106 matched controls	16.1 years	High (9)
Kristal et al (2014)^Citation26	Nested case–control	USA	1,731 prostate cancer cases and 3,203 cohort participants	Not reported	High (8)
Skaaby et al (2014)^Citation27	Prospective cohort	Denmark	12,204 individuals and 133 cases	11.3 years	High (8)
Schenk et al (2014)^Citation29	Nested case–control	USA	1,695 cases and 1,682 matched controls	7 years	High (9)
Sawada et al (2017)^Citation28	Nested case–control	Japan	201 cases and 402 matched controls	12.8 years	High (7)

Note: The quality was rated by NOS and studies scoring at least 6 stars were classified as high-quality studies.

Abbreviation: NOS, Newcastle–Ottawa Scale.

Figure 2 Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer.

Note: Weights are from random effects analysis.
Abbreviations: 25[OH]D, 25-hydroxyvitamin D; CI, confidence interval; RR, relative risk.

Table 2 The results of subgroup analysis between 25[OH]D concentration and risk of prostate cancer

Subgroups	Number of studies	Number of cases/participants	RR and 95% CI (higher vs lower)	RR and 95% CI (per 10 ng/mL increment)	Heterogeneity (I^2, P-value)
All studies	19	12,824/35,583	1.15 (1.06–1.24)	1.04 (1.02–1.06)	0%, 0.725
Study size
Small	7	1,207/8,999	1.00 (0.79–1.28)	0.99 (0.93–1.05)	0%, 0.746
Large	12	11,617/26,584	1.17 (1.07–1.27)	1.04 (1.02–1.06)	0%, 0.601
Publication year
Before 2010	9	3,129/7,896	1.25 (1.07–1.48)	1.03 (0.99–1.10)	0%, 0.487
After 2010	10	9,695/27,687	1.12 (1.02–1.22)	1.06 (1.02–1.10)	0%, 0.825
Study designs
Cohort	3	500/7,771	1.08 (0.78–1.49)	0.99 (0.89–1.12)	0%, 0.597
Nested case–control	16	12,324/27,812	1.15 (1.06–1.25)	1.05 (1.02–1.09)	0%, 0.654
Adjusted for calcium intake
Adjusted	5	2,963/6,691	1.27 (1.08–1.50)	1.10 (1.02–1.18)	0%, 0.965
Not adjusted	14	9,861/28,892	1.11 (1.02–1.22)	1.03 (1.00–1.08)	0%, 0.570

Abbreviations: 25[OH]D, 25-hydroxyvitamin D; CI, confidence interval; RR, relative risk.

Figure 3 Nonlinear dose–response relationship between 25[OH]D concentration and risk of prostate cancer.

Abbreviations: 25[OH]D, 25-hydroxyvitamin D; RR, relative risk.

Figure 4 Linear dose–response relationship between circulating 25[OH]D concentration and prostate cancer.

Note: Weights are from random effects analysis.
Abbreviations: 25[OH]D, 25-hydroxyvitamin D; CI, confidence interval; RR, relative risk.

Figure 5 The funnel plot in the dose–response meta-analysis did not detect publication bias.

Abbreviations: RR, relative risk; SE, standard error.

BraunMMHelzlsouerKJHollisBWComstockGWProstate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States)Cancer Causes Control1995632352397612803

 PubMed Web of Science ®Google Scholar

NomuraAMStemmermannGNLeeJSerum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States)Cancer Causes Control1998944254329794175

 PubMed Web of Science ®Google Scholar

TuohimaaPTenkanenLAhonenMBoth high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case–control study in the Nordic countriesInt J Cancer2004108110410814618623

 PubMed Web of Science ®Google Scholar

PlatzEALeitzmannMFHollisBWWillettWCGiovannucciEPlasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancerCancer Causes Control200415325526515090720

 PubMed Web of Science ®Google Scholar

JacobsETGiulianoARMartinezMEHollisBWReidMEMarshallJRPlasma levels of 25-hydroxyvitamin D, 125-dihydroxyvitamin D and the risk of prostate cancerJ Steroid Biochem Mol Biol200489–901–5533537

 Web of Science ®Google Scholar

BaronJABeachMWallaceKRisk of prostate cancer in a randomized clinical trial of calcium supplementationCancer Epidemiol Biomarkers Prev200514358658915767334

 PubMed Web of Science ®Google Scholar

Faupel-BadgerJMDiawLAlbanesDVirtamoJWoodsonKTangreaJALack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in Finnish menCancer Epidemiol Biomarkers Prev200716122784278618086789

 PubMed Web of Science ®Google Scholar

AhnJPetersUAlbanesDProstate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project TeamSerum vitamin D concentration and prostate cancer risk: a nested case–control studyJ Natl Cancer Inst20081001179680418505967

 PubMedGoogle Scholar

TravisRCCroweFLAllenNESerum vitamin D and risk of prostate cancer in a case–control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)Am J Epidemiol2009169101223123219359375

 PubMed Web of Science ®Google Scholar

ParkSYCooneyRVWilkensLRMurphySPHendersonBEKolonelLNPlasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohortEur J Cancer201046593293620064705

 PubMed Web of Science ®Google Scholar

BarnettCMNielsonCMShannonJSerum 25-OH vitamin D levels and risk of developing prostate cancer in older menCancer Causes Control20102181297130320383574

 PubMed Web of Science ®Google Scholar

AlbanesDMondulAMYuKSerum 25-hydroxy vitamin D and prostate cancer risk in a large nested case–control studyCancer Epidemiol Biomarkers Prev20112091850186021784952

 PubMed Web of Science ®Google Scholar

BrandstedtJAlmquistMManjerJMalmJVitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case–control studyCancer Causes Control20122381377138522706676

 PubMed Web of Science ®Google Scholar

ShuiIMMucciLAKraftPVitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case–control studyJ Natl Cancer Inst2012104969069922499501

 PubMedGoogle Scholar

MeyerHERobsahmTEBjorgeTBrustadMBlomhoffRVitamin D, season, and risk of prostate cancer: a nested case–control study within Norwegian health studiesAm J Clin Nutr201397114715423193007

 PubMed Web of Science ®Google Scholar

KristalARTillCSongXPlasma vitamin D and prostate cancer risk: results from the selenium and vitamin E cancer prevention trialCancer Epidemiol Biomarkers Prev20142381494150424732629

 PubMed Web of Science ®Google Scholar

SkaabyTHusemoenLLThuesenBHProspective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancerCancer Epidemiol Biomarkers Prev20142371220122924789846

 PubMed Web of Science ®Google Scholar

SchenkJMTillCATangenCMSerum 25-hydroxyvitamin D concentrations and risk of prostate cancer: results from the prostate cancer prevention trialCancer Epidemiol Biomarkers Prev20142381484149325085836

 PubMed Web of Science ®Google Scholar

SawadaNInoueMIwasakiMPlasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested case–control study in Japan: the JPHC studyEur J Clin Nutr201771113213627759068

 PubMed Web of Science ®Google Scholar