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Published in: Cancer Causes & Control 5/2016

01-05-2016 | Original paper

Vitamin D, PTH, and calcium in relation to survival following prostate cancer

Authors: Johan Brändstedt, Martin Almquist, Jonas Manjer, Johan Malm

Published in: Cancer Causes & Control | Issue 5/2016

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Abstract

Purpose

Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer.

Methods

We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score).

Results

We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85–102 nmol/L) compared to the first (<68 nmol/L), HR 0.54 (0.34–0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22–0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35–2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32–0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer mortality.

Conclusion

This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may improve survival in men with prostate cancer.
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Literature
1.
go back to reference Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10(5A):1307–1311PubMed Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10(5A):1307–1311PubMed
2.
go back to reference Moreno J, Krishnan AV, Peehl DM, Feldman D (2006) Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway. Anticancer Res 26(4A):2525–2530PubMed Moreno J, Krishnan AV, Peehl DM, Feldman D (2006) Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway. Anticancer Res 26(4A):2525–2530PubMed
4.
go back to reference 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 Caner 128(6):1414–1424CrossRef 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 Caner 128(6):1414–1424CrossRef
5.
go back to reference 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 Cause Control 22(3):319–340. doi:10.1007/s10552-010-9706-3 CrossRef 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 Cause Control 22(3):319–340. doi:10.​1007/​s10552-010-9706-3 CrossRef
7.
go back to reference Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z (2014) Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. J Cancer Res Clin 140(9):1465–1477. doi:10.1007/s00432-014-1706-3 CrossRef Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z (2014) Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. J Cancer Res Clin 140(9):1465–1477. doi:10.​1007/​s00432-014-1706-3 CrossRef
9.
go back to reference 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 I 104(9):690–699. doi:10.1093/jnci/djs189 CrossRef 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 I 104(9):690–699. doi:10.​1093/​jnci/​djs189 CrossRef
13.
go back to reference 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 Biomar 20(9):1850–1860. doi:10.1158/1055-9965.EPI-11-0403 CrossRef 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 Biomar 20(9):1850–1860. doi:10.​1158/​1055-9965.​EPI-11-0403 CrossRef
15.
go back to reference Shui IM, Mondul AM, Lindstrom S, Tsilidis KK, Travis RC, Gerke T, Albanes D, Mucci LA, Giovannucci E, Kraft P, For the B, Prostate Cancer Cohort Consortium G (2015) Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. Cancer. doi:10.1002/cncr.29320 Shui IM, Mondul AM, Lindstrom S, Tsilidis KK, Travis RC, Gerke T, Albanes D, Mucci LA, Giovannucci E, Kraft P, For the B, Prostate Cancer Cohort Consortium G (2015) Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. Cancer. doi:10.​1002/​cncr.​29320
16.
go back to reference Ritchie CK, Thomas KG, Andrews LR, Tindall DJ, Fitzpatrick LA (1997) Effects of the calciotrophic peptides calcitonin and parathyroid hormone on prostate cancer growth and chemotaxis. Prostate 30(3):183–187CrossRefPubMed Ritchie CK, Thomas KG, Andrews LR, Tindall DJ, Fitzpatrick LA (1997) Effects of the calciotrophic peptides calcitonin and parathyroid hormone on prostate cancer growth and chemotaxis. Prostate 30(3):183–187CrossRefPubMed
17.
go back to reference Iwamura M, Abrahamsson PA, Foss KA, Wu G, Cockett AT, Deftos LJ (1994) Parathyroid hormone-related protein: a potential autocrine growth regulator in human prostate cancer cell lines. Urology 43(5):675–679CrossRefPubMed Iwamura M, Abrahamsson PA, Foss KA, Wu G, Cockett AT, Deftos LJ (1994) Parathyroid hormone-related protein: a potential autocrine growth regulator in human prostate cancer cell lines. Urology 43(5):675–679CrossRefPubMed
20.
go back to reference Giovannucci E, Liu Y, Platz EA, Stampfer MJ, Willett WC (2007) Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer J 121(7):1571–1578CrossRef Giovannucci E, Liu Y, Platz EA, Stampfer MJ, Willett WC (2007) Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer J 121(7):1571–1578CrossRef
21.
go back to reference Tseng M, Breslow RA, Graubard BI, Ziegler RG (2005) Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 81(5):1147–1154PubMed Tseng M, Breslow RA, Graubard BI, Ziegler RG (2005) Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 81(5):1147–1154PubMed
23.
go back to reference Brandstedt J, Almquist M, Ulmert D, Manjer J, Malm J (2016) Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study. Cancer Causes Control 27(1):69–80. doi:10.1007/s10552-015-0684-3 CrossRefPubMed Brandstedt J, Almquist M, Ulmert D, Manjer J, Malm J (2016) Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study. Cancer Causes Control 27(1):69–80. doi:10.​1007/​s10552-015-0684-3 CrossRefPubMed
24.
go back to reference Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M, Mattisson I, Berglund G (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499CrossRefPubMed Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M, Mattisson I, Berglund G (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499CrossRefPubMed
25.
go back to reference Anker P, Wieland E, Ammann D, Dohner RE, Asper R, Simon W (1981) Neutral carrier based ion-selective electrode for the determination of total calcium in blood serum. Anal Chem 53(13):1970–1974CrossRefPubMed Anker P, Wieland E, Ammann D, Dohner RE, Asper R, Simon W (1981) Neutral carrier based ion-selective electrode for the determination of total calcium in blood serum. Anal Chem 53(13):1970–1974CrossRefPubMed
27.
go back to reference Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C (2009) Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int J Environ Res Public Health 6(10):2585–2607CrossRefPubMedPubMedCentral Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C (2009) Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int J Environ Res Public Health 6(10):2585–2607CrossRefPubMedPubMedCentral
28.
go back to reference Samverkan RCI (2012) Nationell kvalitetsrapport för diagnosår 2012 från Nationella prostatacancerregistret (NPCR) Samverkan RCI (2012) Nationell kvalitetsrapport för diagnosår 2012 från Nationella prostatacancerregistret (NPCR)
29.
go back to reference Andren O, Fall K, Franzen L, Andersson SO, Johansson JE, Rubin MA (2006) How well does the Gleason score predict prostate cancer death? A 20-year followup of a population based cohort in Sweden. J Urol 175(4):1337–1340. doi:10.1016/S0022-5347(05)00734-2 CrossRefPubMed Andren O, Fall K, Franzen L, Andersson SO, Johansson JE, Rubin MA (2006) How well does the Gleason score predict prostate cancer death? A 20-year followup of a population based cohort in Sweden. J Urol 175(4):1337–1340. doi:10.​1016/​S0022-5347(05)00734-2 CrossRefPubMed
30.
go back to reference Schwartz GG (2013) Vitamin D, sunlight, and the epidemiology of prostate cancer. Anticancer Agents Med Chem 13(1):45–57CrossRefPubMed Schwartz GG (2013) Vitamin D, sunlight, and the epidemiology of prostate cancer. Anticancer Agents Med Chem 13(1):45–57CrossRefPubMed
34.
go back to reference Zhou W, Heist RS, Liu G, Neuberg DS, Asomaning K, Su L, Wain JC, Lynch TJ, Giovannucci E, Christiani DC (2006) Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomar 15(11):2239–2245. doi:10.1158/1055-9965.EPI-06-0023 CrossRef Zhou W, Heist RS, Liu G, Neuberg DS, Asomaning K, Su L, Wain JC, Lynch TJ, Giovannucci E, Christiani DC (2006) Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomar 15(11):2239–2245. doi:10.​1158/​1055-9965.​EPI-06-0023 CrossRef
36.
go back to reference Skinner HG, Schwartz GG (2009) A prospective study of total and ionized serum calcium and fatal prostate cancer. Cancer Epidemiol Biomar 18(2):575–578CrossRef Skinner HG, Schwartz GG (2009) A prospective study of total and ionized serum calcium and fatal prostate cancer. Cancer Epidemiol Biomar 18(2):575–578CrossRef
37.
go back to reference Van Hemelrijck M, Hermans R, Michaelsson K, Melvin J, Garmo H, Hammar N, Jungner I, Walldius G, Holmberg L (2012) Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study. Cancer Causes Control 23(8):1349–1358. doi:10.1007/s10552-012-0015-x CrossRefPubMed Van Hemelrijck M, Hermans R, Michaelsson K, Melvin J, Garmo H, Hammar N, Jungner I, Walldius G, Holmberg L (2012) Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study. Cancer Causes Control 23(8):1349–1358. doi:10.​1007/​s10552-012-0015-x CrossRefPubMed
38.
go back to reference Halthur C, Johansson AL, Almquist M, Malm J, Gronberg H, Manjer J, Dickman PW (2009) Serum calcium and the risk of prostate cancer. Cancer Causes Control 20(7):1205–1214CrossRefPubMed Halthur C, Johansson AL, Almquist M, Malm J, Gronberg H, Manjer J, Dickman PW (2009) Serum calcium and the risk of prostate cancer. Cancer Causes Control 20(7):1205–1214CrossRefPubMed
39.
go back to reference Kristal AR, Cohen JH, Qu P, Stanford JL (2002) Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomar 11(8):719–725 Kristal AR, Cohen JH, Qu P, Stanford JL (2002) Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomar 11(8):719–725
40.
go back to reference Gao X, LaValley MP, Tucker KL (2005) Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer I 97(23):1768–1777. doi:10.1093/jnci/dji402 CrossRef Gao X, LaValley MP, Tucker KL (2005) Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer I 97(23):1768–1777. doi:10.​1093/​jnci/​dji402 CrossRef
42.
go back to reference Snowdon DA, Phillips RL, Choi W (1984) Diet, obesity, and risk of fatal prostate cancer. Am J Epidemiol 120(2):244–250PubMed Snowdon DA, Phillips RL, Choi W (1984) Diet, obesity, and risk of fatal prostate cancer. Am J Epidemiol 120(2):244–250PubMed
43.
go back to reference Cole DE, Peltekova VD, Rubin LA, Hawker GA, Vieth R, Liew CC, Hwang DM, Evrovski J, Hendy GN (1999) A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations. Lancet 353(9147):112–115CrossRefPubMed Cole DE, Peltekova VD, Rubin LA, Hawker GA, Vieth R, Liew CC, Hwang DM, Evrovski J, Hendy GN (1999) A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations. Lancet 353(9147):112–115CrossRefPubMed
44.
go back to reference Murray RM, Grill V, Crinis N, Ho PW, Davison J, Pitt P (2001) Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 86(9):4133–4138CrossRefPubMed Murray RM, Grill V, Crinis N, Ho PW, Davison J, Pitt P (2001) Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 86(9):4133–4138CrossRefPubMed
46.
go back to reference Barlow L, Westergren K, Holmberg L, Talback M (2009) The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 48(1):27–33CrossRefPubMed Barlow L, Westergren K, Holmberg L, Talback M (2009) The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 48(1):27–33CrossRefPubMed
47.
48.
go back to reference Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MP (2010) Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomar 19(4):927–931. doi:10.1158/1055-9965.EPI-09-1121 CrossRef Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MP (2010) Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomar 19(4):927–931. doi:10.​1158/​1055-9965.​EPI-09-1121 CrossRef
49.
go back to reference van Schoor NM, Knol DL, Deeg DJ, Peters FP, Heijboer AC, Lips P (2014) Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels in different age groups: results of the Longitudinal Aging Study Amsterdam. Osteoporos Int 25(5):1483–1491. doi:10.1007/s00198-014-2651-3 PubMed van Schoor NM, Knol DL, Deeg DJ, Peters FP, Heijboer AC, Lips P (2014) Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels in different age groups: results of the Longitudinal Aging Study Amsterdam. Osteoporos Int 25(5):1483–1491. doi:10.​1007/​s00198-014-2651-3 PubMed
50.
go back to reference Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, Minchinela J, Perich C, Simon M (1999) Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Investig 59(7):491–500CrossRef Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, Minchinela J, Perich C, Simon M (1999) Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Investig 59(7):491–500CrossRef
51.
go back to reference Gallagher SK, Johnson LK, Milne DB (1989) Short-term and long-term variability of indices related to nutritional status. I: Ca, Cu, Fe, Mg, and Zn. Clin Chem 35(3):369–373PubMed Gallagher SK, Johnson LK, Milne DB (1989) Short-term and long-term variability of indices related to nutritional status. I: Ca, Cu, Fe, Mg, and Zn. Clin Chem 35(3):369–373PubMed
52.
go back to reference Ankrah-Tetteh T, Wijeratne S, Swaminathan R (2008) Intraindividual variation in serum thyroid hormones, parathyroid hormone and insulin-like growth factor-1. Ann Clin Biochem 45(Pt 2):167–169CrossRefPubMed Ankrah-Tetteh T, Wijeratne S, Swaminathan R (2008) Intraindividual variation in serum thyroid hormones, parathyroid hormone and insulin-like growth factor-1. Ann Clin Biochem 45(Pt 2):167–169CrossRefPubMed
53.
go back to reference Viljoen A, Singh DK, Twomey PJ, Farrington K (2008) Analytical quality goals for parathyroid hormone based on biological variation. Clin Chem Lab Med 46(10):1438–1442CrossRefPubMed Viljoen A, Singh DK, Twomey PJ, Farrington K (2008) Analytical quality goals for parathyroid hormone based on biological variation. Clin Chem Lab Med 46(10):1438–1442CrossRefPubMed
55.
go back to reference Brock K, Huang WY, Fraser DR, Ke L, Tseng M, Stolzenberg-Solomon R, Peters U, Ahn J, Purdue M, Mason RS, McCarty C, Ziegler RG, Graubard B (2010) Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women. J Steroid Biochem 121(1–2):462–466. doi:10.1016/j.jsbmb.2010.03.091 CrossRef Brock K, Huang WY, Fraser DR, Ke L, Tseng M, Stolzenberg-Solomon R, Peters U, Ahn J, Purdue M, Mason RS, McCarty C, Ziegler RG, Graubard B (2010) Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women. J Steroid Biochem 121(1–2):462–466. doi:10.​1016/​j.​jsbmb.​2010.​03.​091 CrossRef
56.
go back to reference Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporosis Int 16(11):1425–1431. doi:10.1007/s00198-005-1860-1 CrossRef Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporosis Int 16(11):1425–1431. doi:10.​1007/​s00198-005-1860-1 CrossRef
Metadata
Title
Vitamin D, PTH, and calcium in relation to survival following prostate cancer
Authors
Johan Brändstedt
Martin Almquist
Jonas Manjer
Johan Malm
Publication date
01-05-2016
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 5/2016
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-016-0740-7

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