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Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case–control study

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Abstract

Objective

To examine the risk of prostate cancer in relation to pre-diagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH, and calcium.

Methods

Nine hundred forty-three incident prostate cancer cases were identified in the Malmö Diet and Cancer Study cohort, and each was matched with one control using incidence density matching with age as the underlying timescale. We also matched for calendar time and age at inclusion. Logistic regression analysis yielded odds ratios with 95 % confidence intervals for different quartiles and deciles. All analyses were repeated stratified for age and body mass index (BMI).

Results

We found a weak trend toward increasing prostate cancer risk with rising vitamin D levels (p-trend across quartiles, 0.048). Dividing the cohort into deciles showed a nonlinear association. Compared to decile one, the prostate cancer risk was highest in deciles seven and eight, which corresponded to vitamin D levels of 91–97 nmol/L (1.68; 1.06–2.68), and 98–106 nmol/L (1.80; 1.13–2.85). In the other deciles, there was no association between prostate cancer risk and vitamin D levels. Albumin-adjusted calcium was positively associated with an increased risk for prostate cancer among men aged 55–65 with a BMI <25 (2.07; 1.08–3.97). No association was observed between pre-diagnostic PTH and subsequent prostate cancer incidence, and the stratified analyses revealed no other convincing relationships.

Conclusions

This study suggests a possible weak positive nonlinear association between vitamin D and the risk of prostate cancer.

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References

  1. Gronberg H (2003) Prostate cancer epidemiology. Lancet 361(9360):859–864

    Article  PubMed  Google Scholar 

  2. Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10(5A):1307–1311

    PubMed  CAS  Google Scholar 

  3. Krishnan AV, Moreno J, Nonn L, Swami S, Peehl DM, Feldman D (2007) Calcitriol as a chemopreventive and therapeutic agent in prostate cancer: role of anti-inflammatory activity. J Bone Miner Res 22(Suppl 2):V74–V80

    Article  PubMed  CAS  Google Scholar 

  4. Schwartz GG, Wang MH, Zang M, Singh RK, Siegal GP (1997) 1 alpha,25-Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 6(9):727–732

    PubMed  CAS  Google Scholar 

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G et al (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

    Article  PubMed  CAS  Google Scholar 

  7. Albanes D, Weinstein SJ, Mondul AM, Virtamo J (2011) Circulating Vitamin D and risk of prostate cancer—response. Cancer Epidemiol Biomarkers Prev. Epub 2011/11/03

  8. Corder EH, Guess HA, Hulka BS, Friedman GD, Sadler M, Vollmer RT et al (1993) Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 2(5):467–472

    PubMed  CAS  Google Scholar 

  9. Gann PH, Ma J, Hennekens CH, Hollis BW, Haddad JG, Stampfer MJ (1996) Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev 5(2):121–126

    PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  Google Scholar 

  11. Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D et al (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med 4(3):e103

    Article  PubMed  Google Scholar 

  12. Nomura AM, Stemmermann GN, Lee J, Kolonel LN, Chen TC, Turner A et al (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Cancer Causes Control 9(4):425–432

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  Google Scholar 

  14. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al. 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

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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):183–187

    Article  PubMed  CAS  Google Scholar 

  17. Liao J, Schneider A, Datta NS, McCauley LK (2006) Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66(18):9065–9073

    Article  PubMed  CAS  Google Scholar 

  18. Fedirko V, Riboli E, Bueno-de-Mesquita HB, Rinaldi S, Pischon T, Norat T, et al. Pre-diagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Cancer Epidemiol Biomarkers Prev

  19. Schwartz GG (2008) Prostate cancer, serum parathyroid hormone, and the progression of skeletal metastases. Cancer Epidemiol Biomarkers Prev 17(3):478–483. Epub 2008/03/20

    Google Scholar 

  20. 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):4133–4138. Epub 2001/09/11

    Google Scholar 

  21. Giovannucci E, Rimm EB, Wolk A, Ascherio A, Stampfer MJ, Colditz GA et al (1998) Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 58(3):442–447

    PubMed  CAS  Google Scholar 

  22. Skinner HG, Schwartz GG (2009) A prospective study of total and ionized serum calcium and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 18(2):575–578

    Article  PubMed  CAS  Google Scholar 

  23. Skinner HG, Schwartz GG (2008) Serum calcium and incident and fatal prostate cancer in the National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev 17(9):2302–2305. Epub 2008/09/05

    Google Scholar 

  24. 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 121(7):1571–1578

    Article  PubMed  CAS  Google Scholar 

  25. Wright ME, Chang SC, Schatzkin A, Albanes D, Kipnis V, Mouw T et al (2007) Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 109(4):675–684

    Article  PubMed  Google Scholar 

  26. Halthur C, Johansson AL, Almquist M, Malm J, Gronberg H, Manjer J et al (2009) Serum calcium and the risk of prostate cancer. Cancer Causes Control 20(7):1205–1214

    Article  PubMed  CAS  Google Scholar 

  27. Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M et al (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499

    Article  PubMed  CAS  Google Scholar 

  28. Wallstrom P (2002) Diet, lifestyle, antioxidants and biomarkers of cancer risk. An epidemiological report from the Malmö Diet and cancer cohort. Thesis, Lund University, Malmö

  29. 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):1970–1974

    Article  PubMed  CAS  Google Scholar 

  30. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP et al (2007) The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 85(3):649–650

    PubMed  CAS  Google Scholar 

  31. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N et al (2008) Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst 100(11):796–804

    Article  PubMed  CAS  Google Scholar 

  32. Dusso AS, Brown AJ, Slatopolsky E (2005) Vitamin D. Am J Physiol Renal Physiol 289(1):F8–F28

    Article  PubMed  CAS  Google Scholar 

  33. Pero RW, Olsson A, Bryngelsson C, Carlsson S, Janzon L, Berglund G et al (1998) Quality control program for storage of biologically banked blood specimens in the Malmo Diet and Cancer Study. Cancer Epidemiol Biomarkers Prev 7(9):803–808

    PubMed  CAS  Google Scholar 

  34. Hollis BW (2008) Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs. Am J Clin Nutr 88(2):507S–510S

    PubMed  CAS  Google Scholar 

  35. Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV et al (1999) Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 59(7):491–500

    Article  PubMed  CAS  Google Scholar 

  36. 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):369–373

    PubMed  CAS  Google Scholar 

  37. 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):167–169

    Article  PubMed  CAS  Google Scholar 

  38. 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):1438–1442

    Article  PubMed  CAS  Google Scholar 

  39. Nilsson-Ehle P (2003) Laurells klinisk kemi i praktisk medicin: Studentlitteratur AB

  40. Leifsson BG, Ahren B (1996) Serum calcium and survival in a large health screening program. J Clin Endocrinol Metab 81(6):2149–2153. Epub 1996/06/01

    Google Scholar 

  41. Kukreja SC, Shanmugam A, Lad TE (1988) Hypocalcemia in patients with prostate cancer. Calcif Tissue Int 43(6):340–345. Epub 1988/12/01

    Google Scholar 

  42. 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):27–33

    Article  PubMed  Google Scholar 

  43. 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):2585–2607

    Article  PubMed  CAS  Google Scholar 

  44. Hoffman RM, Stone SN, Espey D, Potosky AL (2005) Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA. BMC Cancer 5:27

    Article  PubMed  Google Scholar 

  45. Lund Oci (2006) Kvalitetsregister för prostatacancer, Regional rapport för diagnosår 2006, Södra sjukvårdsregionen

  46. Fang F, Kasperzyk JL, Shui I, Hendrickson W, Hollis BW, Fall K, et al (2011) Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer. PloS one 6(4):e18625. Epub 2011/04/16

    Google Scholar 

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Acknowledgments

This work was supported by grants from the Swedish Research Council (K2007-69X-20487-01-3), the Ernhold Lundström Foundation, the Einar and Inga Nilsson Foundation, Malmö University Hospital Cancer Research Fund, Malmö University Hospital Funds and Donations, the Crafoord Foundation, Region Skåne, the Mossfelt Foundation, Fundacion Federico S.A, the Swedish Cancer Society (CAN 2006/1554), and the Gunnar Nilsson Cancer Foundation.

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Authors and Affiliations

  1. Department of Urology, Skåne University Hospital Malmö, Lund University, 205 02, Malmö, Sweden

    Johan Brändstedt

  2. Department of Surgery, Skåne University Hospital Lund, Lund University, Malmö, Sweden

    Martin Almquist

  3. Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden

    Jonas Manjer

  4. The Malmö Diet and Cancer Study, Lund University, Malmö, Sweden

    Martin Almquist & Jonas Manjer

  5. Department of Laboratory Medicine, Section for Clinical Chemistry, Skåne University Hospital, Lund University, Malmö, Sweden

    Johan Malm

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  1. Johan Brändstedt
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Correspondence to Johan Brändstedt.

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Brändstedt, J., Almquist, M., Manjer, J. et al. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case–control study. Cancer Causes Control 23, 1377–1385 (2012). https://doi.org/10.1007/s10552-012-9948-3

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