Abstract
Purpose
To investigate and clarify the relationship between circulating 25-hydroxyvitamin D level and prostate cancer risk.
Methods
We conducted the meta-analysis to better evaluate the association. Terms “25-Hydroxyvitamin D”/“vitamin D” and “prostate cancer” were used for literature search.
Results
We identified 21 relevant publications from databases of PubMed and MEDLINE and included 11,941 cases and 13,870 controls in the meta-analysis. Overall studies revealed a significant 17 % elevated risk of prostate cancer for individuals with higher level of 25-hydroxyvitamin D (OR = 1.17, 95 % CI = 1.05–1.30, P = 0.004), and no publication bias was found in the calculations (P = 0.629). Subgroup analysis confirmed the association from nested case–control study group, studies from USA group and studies using serum samples group (nested case–control studies: OR = 1.17, 95 % CI = 1.08–1.27, P < 0.001; USA: OR = 1.15, 95 % CI = 1.03–1.29, P = 0.017; serum: OR = 1.20, 95 % CI = 1.01–1.42, P = 0.042); moreover, sensitivity tests also indicated significant results in studies from Europe and studies conducting with plasma samples after exclusion of some influential single study from the analysis, respectively (Europe: OR = 1.21, 95 % CI = 1.04–1.40, P = 0.014; plasma: OR = 1.13, 95 % CI = 1.00–1.27, P = 0.05).
Conclusions
Our meta-analysis, for the first time, suggested significant positive relationship between high level of 25-hydroxyvitamin D and increased risk of prostate cancer, reminding us that more concern should be taken into account during assessing the effect of 25-hydroxyvitamin D.
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Abbreviations
- RR:
-
Relative risk
- OR:
-
Odds ratio
- 95 % CI:
-
95 % Confidential interval
References
Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB, Prostate LC, Ovarian Cancer Screening Trial Project T (2008) Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst 100(11):796–804. doi:10.1093/jnci/djn152
Ahn J, Albanes D, Berndt SI, Peters U, Chatterjee N, Freedman ND, Abnet CC, Huang WY, Kibel AS, Crawford ED, Weinstein SJ, Chanock SJ, Schatzkin A, Hayes RB, Prostate LC, Ovarian Trial Project T (2009) Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk. Carcinogenesis 30(5):769–776. doi:10.1093/carcin/bgp055
Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11(9):847–852
Albanes D, Weinstein SJ, Wright ME, Mannisto S, Limburg PJ, Snyder K, Virtamo J (2009) Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 101(18):1272–1279. doi:10.1093/jnci/djp260
Albanes D, Mondul AM, Yu K, Parisi D, Horst RL, Virtamo J, Weinstein SJ (2011) Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case-control study. Cancer Epidemiol Biomark Prev 20(9):1850–1860. doi:10.1158/1055-9965.EPI-11-0403
Bailey RL, Dodd KW, Goldman JA, Gahche JJ, Dwyer JT, Moshfegh AJ, Sempos CT, Picciano MF (2010) Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr 140(4):817–822. doi:10.3945/jn.109.118539
Barnett CM, Nielson CM, Shannon J, Chan JM, Shikany JM, Bauer DC, Hoffman AR, Barrett-Connor E, Orwoll E, Beer TM (2010) Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men. Cancer Causes Control 21(8):1297–1303. doi:10.1007/s10552-010-9557-y
Baron JA, Beach M, Wallace K, Grau MV, Sandler RS, Mandel JS, Heber D, Greenberg ER (2005) Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomark Prev 14(3):586–589. doi:10.1158/1055-9965.EPI-04-0319
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101
Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB (2004) Effect of Vitamin D on falls: a meta-analysis. JAMA, J Am Med Assoc 291(16):1999–2006. doi:10.1001/jama.291.16.1999
Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:b3692. doi:10.1136/bmj.b3692
Brandstedt J, Almquist M, Manjer J, Malm J (2012) Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study. Cancer Causes Control 23(8):1377–1385. doi:10.1007/s10552-012-9948-3
Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW (1995) Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Cancer Causes Control 6(3):235–239
Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279(5350):563–566
Chuang SC, Stolzenberg-Solomon R, Ueland PM, Vollset SE, Midttun O, Olsen A, Tjonneland A, Overvad K, Boutron-Ruault MC, Morois S, Clavel-Chapelon F, Teucher B, Kaaks R, Weikert C, Boeing H, Trichopoulou A, Benetou V, Naska A, Jenab M, Slimani N, Romieu I, Michaud DS, Palli D, Sieri S, Panico S, Sacerdote C, Tumino R, Skeie G, Duell EJ, Rodriguez L, Molina-Montes E, Huerta JM, Larranaga N, Gurrea AB, Johansen D, Manjer J, Ye W, Sund M, Peeters PH, Jeurnink S, Wareham N, Khaw KT, Crowe F, Riboli E, Bueno-de-Mesquita B, Vineis P (2011) A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer 47(12):1808–1816. doi:10.1016/j.ejca.2011.02.007
Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7(9):684–700. doi:10.1038/nrc2196
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188
Diaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A (2000) Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res 60(8):2304–2312
Donkena KV, Karnes RJ, Young CY (2010) Vitamins and prostate cancer risk. Molecules 15(3):1762–1783. doi:10.3390/molecules15031762
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Elamin MB, Abu Elnour NO, Elamin KB, Fatourechi MM, Alkatib AA, Almandoz JP, Liu H, Lane MA, Mullan RJ, Hazem A, Erwin PJ, Hensrud DD, Murad MH, Montori VM (2011) Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab 96(7):1931–1942. doi:10.1210/jc.2011-0398
Faupel-Badger JM, Diaw L, Albanes D, Virtamo J, Woodson K, Tangrea JA (2007) Lack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in Finnish men. Cancer Epidemiol Biomark Prev 16(12):2784–2786. doi:10.1158/1055-9965.EPI-07-0672
Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P (2011) Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 128(6):1414–1424. doi:10.1002/ijc.25439
Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE, Fraser WD, Sterne JA, Metcalfe C (2011) Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control 22(3):319–340. doi:10.1007/s10552-010-9706-3
Gilbert R, Metcalfe C, Fraser WD, Donovan J, Hamdy F, Neal DE, Lane JA, Martin RM (2012) Associations of circulating 25-hydroxyvitamin D with prostate cancer diagnosis, stage and grade. Int J Cancer 131(5):1187–1196. doi:10.1002/ijc.27327
Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16(2):83–95. doi:10.1007/s10552-004-1661-4
Grant WB, Garland CF (2006) The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res 26(4A):2687–2699
Hypponen E, Boucher BJ, Berry DJ, Power C (2008) 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes 57(2):298–305. doi:10.2337/db07-1122
Jacobs ET, Giuliano AR, Martinez ME, Hollis BW, Reid ME, Marshall JR (2004) Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer. J Steroid Biochem Mol Biol 89–90(1–5):533–537. doi:10.1016/j.jsbmb.2004.03.063
Kim YI (2006) Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut 55(10):1387–1389. doi:10.1136/gut.2006.095463
Lamprecht SA, Lipkin M (2003) Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer 3(8):601–614. doi:10.1038/nrc1144
Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med 4(3):e103. doi:10.1371/journal.pmed.0040103
Lucock M, Yates Z (2009) Folic acid fortification: a double-edged sword. Curr Opin Clin Nutr Metab Care 12(6):555–564. doi:10.1097/MCO.0b013e32833192bc
Ma J, Stampfer MJ, Gann PH, Hough HL, Giovannucci E, Kelsey KT, Hennekens CH, Hunter DJ (1998) Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomark Prev 7(5):385–390
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748
Meyer HE, Robsahm TE, Bjorge T, Brustad M, Blomhoff R (2013) Vitamin D, season, and risk of prostate cancer: a nested case-control study within Norwegian health studies. Am J Clin Nutr 97(1):147–154. doi:10.3945/ajcn.112.039222
Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E (2007) Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Prostate 67(9):911–923. doi:10.1002/pros.20570
Mitrou PN, Albanes D, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Leitzmann MF (2007) A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). Int J Cancer 120(11):2466–2473. doi:10.1002/ijc.22553
Mohr SB, Gorham ED, Alcaraz JE, Kane CJ, Macera CA, Parsons JK, Wingard DL, Garland CF (2011) Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis. Anticancer Res 31(9):2939–2948
Nakagawa K, Sasaki Y, Kato S, Kubodera N, Okano T (2005) 22-Oxa-1alpha, 25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer. Carcinogenesis 26(6):1044–1054. doi:10.1093/carcin/bgi049
Nomura AM, Stemmermann GN, Lee J, Kolonel LN, Chen TC, Turner A, Holick MF (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes Control 9(4):425–432
Ordonez-Mena JM, Schottker B, Haug U, Muller H, Kohrle J, Schomburg L, Holleczek B, Brenner H (2013) Serum 25-hydroxyvitamin d and cancer risk in older adults: results from a large German prospective cohort study. Cancer Epidemiol Biomark Prev 22(5):905–916. doi:10.1158/1055-9965.EPI-12-1332
Park SY, Cooney RV, Wilkens LR, Murphy SP, Henderson BE, Kolonel LN (2010) Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort. Eur J Cancer 46(5):932–936. doi:10.1016/j.ejca.2009.12.030
Pazdiora P, Svobodova S, Fuchsova R, Kucera R, Prazakova M, Vrzalova J, Narsanska A, Strakova M, Treskova I, Pecen L, Treska V, Holubec L Jr, Pesek M, Finek J, Topolcan O (2011) Vitamin D in colorectal, breast, prostate and lung cancer: a pilot study. Anticancer Res 31(10):3619–3621
Pittas AG, Lau J, Hu FB, Dawson-Hughes B (2007) The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92(6):2017–2029. doi:10.1210/jc.2007-0298
Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E (2004) Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control 15(3):255–265. doi:10.1023/B:CACO.0000024245.24880.8a
Porojnicu AC, Robsahm TE, Dahlback A, Berg JP, Christiani D, Bruland OS, Moan J (2007) Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? Lung Cancer 55(3):263–270. doi:10.1016/j.lungcan.2006.11.013
Schottker B, Ball D, Gellert C, Brenner H (2013) Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev 12(2):708–718. doi:10.1016/j.arr.2012.02.004
Shui IM, Mucci LA, Kraft P, Tamimi RM, Lindstrom S, Penney KL, Nimptsch K, Hollis BW, Dupre N, Platz EA, Stampfer MJ, Giovannucci E (2012) Vitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case-control study. J Natl Cancer Inst 104(9):690–699. doi:10.1093/jnci/djs189
Siddiqui E, Mumtaz FH, Gelister J (2004) Understanding prostate cancer. J R Soc Promot Health 124(5):219–221
Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics 2014. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208
Society AC (2011) Global cancer facts & figures, 2nd edn. American Cancer Society, Atlanta
Society AC (2013) Cancer facts & figures 2013. American Cancer Society, Atlanta
Stattin P, Bylund A, Rinaldi S, Biessy C, Dechaud H, Stenman UH, Egevad L, Riboli E, Hallmans G, Kaaks R (2000) Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst 92(23):1910–1917
Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjonneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kroger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larranaga N, Gonzalez CA, Arguelles MV, Sanchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ (2009) Serum 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 Epidemiol 169(10):1223–1232. doi:10.1093/aje/kwp022
Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M (2004) Both 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 countries. Int J Cancer 108(1):104–108. doi:10.1002/ijc.11375
Tuohimaa P, Tenkanen L, Syvala H, Lumme S, Hakulinen T, Dillner J, Hakama M (2007) Interaction of factors related to the metabolic syndrome and vitamin D on risk of prostate cancer. Cancer Epidemiol Biomark Prev 16(2):302–307. doi:10.1158/1055-9965.EPI-06-0777
Yin L, Raum E, Haug U, Arndt V, Brenner H (2009) Meta-analysis of longitudinal studies: serum vitamin D and prostate cancer risk. Cancer Epidemiol 33(6):435–445. doi:10.1016/j.canep.2009.10.014
Yin L, Ordonez-Mena JM, Chen T, Schottker B, Arndt V, Brenner H (2013) Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Prev Med 57(6):753–764. doi:10.1016/j.ypmed.2013.08.026
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Yonghua Xu and Xiaoping Shao have contributed equally to this study.
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Xu, Y., Shao, X., Yao, Y. et al. Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. J Cancer Res Clin Oncol 140, 1465–1477 (2014). https://doi.org/10.1007/s00432-014-1706-3
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DOI: https://doi.org/10.1007/s00432-014-1706-3