Cancer Causes & Control

, Volume 11, Issue 9, pp 859–867 | Cite as

Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland)

  • June M. Chan
  • Pirjo Pietinen
  • Mikko Virtanen
  • Nea Malila
  • Joseph Tangrea
  • Demetrius Albanes
  • Jarmo Virtamo


Background:Calcium, phosphorus, fructose, and animal protein are hypothesized to be associated with prostate cancer risk, potentially via their influence on 1,25-dihydroxyvitamin D3. We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC Study).

Materials and methods:The ATBC Study was a randomized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers; 27,062 of the men completed a food-use questionnaire at baseline, and comprise the current study population. There were 184 incident clinical (stage 2–4) prostate cancer cases diagnosed between 1985 and 1993. We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer.

Results:We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk. However, men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 (95% CI 0.3–1.0) compared to men with lower intakes of both nutrients, adjusting for age, smoking, body mass index, total energy, education, and supplementation group. Of the other foods and nutrients examined, none was significantly associated with risk.

Discussion:This study provides, at best, only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk, but suggests that there may be an interaction between these nutrients.

calcium diet fructose phosphorus prostate cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    American Cancer Society (1997) Cancer Facts and Figures-1997. Atlanta, GA: American Cancer Society.Google Scholar
  2. 2.
    International Agency for Research on Cancer (1997) Cancer Incidence in Five Continents, Vol. VII. In: Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, eds. IARC Scientific Publications no. 143. Lyon: International Agency for Research on Cancer and International Association of Cancer Registries, World Health Organization, Lyon.Google Scholar
  3. 3.
    Finnish Cancer Registry (1997) Cancer Incidence in Finland 1995; Cancer Statistics of the National Research and Development Centre for Welfare and Health. Helsinki: Cancer Society of Finland; Report no.: publication no. 58.Google Scholar
  4. 4.
    Giovannucci E (1996) How is individual risk for prostate cancer assessed? Hematol Oncol Clin N Am 10: 537–548.Google Scholar
  5. 5.
    Giovannucci E (1998) Diet, 1,25(OH)2 vitamin D and prostate cancer: a hypothesis. Cancer Causes Control 9: 567–583.Google Scholar
  6. 6.
    Hanchette CL, Schwartz GG (1992) Geographic patterns of prostate cancer mortality. Cancer 70: 2861–2869.Google Scholar
  7. 7.
    Ingles SA, Ross RK, Yu MC, et al. (1997) Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89: 166–170.Google Scholar
  8. 8.
    Feldman D, Skowronski RJ, Peehl DM (1995) Vitamin D and prostate cancer. In: American Institute for Cancer Research, editor. Diet and Cancer: Molecular Mechanisms of Interactions. New York: Plenum Press, pp. 53–63.Google Scholar
  9. 9.
    Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 10: 1307–1311.Google Scholar
  10. 10.
    Skowronski RJ, Peehl DM, Feldman D (1993) Vitamin D and prostate cancer: 1,25–dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 132: 1952–1960.Google Scholar
  11. 11.
    Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D (1994) Antiproliferative e.ects of 1,25–dihydroxyvita-min D3 on primary cultures of human prostatic cells. Cancer Res 54: 805–810.Google Scholar
  12. 12.
    Hsieh T-C, Ng C-Y, Mallouh C, Tazaki H, Wu JM (1996) Regulation of growth, PSA/PAP and androgen receptor expres-sion by 1a,25–dihydroxyvitamin D3 in androgen-dependent LNCaP cells. Biochem Biophys Res Commun 223: 141–146.Google Scholar
  13. 13.
    Esquenet M, Swinnen JV, Heyns W, Verhoeven G (1996) Control of LNCaP proliferation and di.erentiation: actions and interac-tions of androgens, 1alpha,25–dihydroxycholecalciferol, all-trans retinoic acid, 9–cis retinoic acid, and phenylacetate. Prostate 28: 182–194.Google Scholar
  14. 14.
    Miller GJ, Stapleton GE, Hedlund TE, Moffatt KA (1995) Vitamin D receptor expression, 24–hydroxylase activity, and inhibition of growth by 1a,25–dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res 1: 997–1003.Google Scholar
  15. 15.
    Bahnson RR, Oeler T, Trump D, Smith D, Schwartz GG (1993) Inhibition of human prostatic carcinoma cell lines by 1,25–dihydroxyvitamin D3 and vitamin D analogs (abstract). J Urol 149 (Suppl.): 471a.Google Scholar
  16. 16.
    Holick MF. Vitamin D (1999) In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th edn. Baltimore, MD: Williams & Wilkins, pp. 329–345.Google Scholar
  17. 17.
    Mayes PA (1993) Intermediary metabolism of fructose. Am J Clin Nutr 58 (Suppl): 754S-765S.Google Scholar
  18. 18.
    Langman CB (1989) Calcitriol metabolism during chronic meta-bolic acidosis. Semin Nephrol 9: 65–71.Google Scholar
  19. 19.
    Brosnan JT, Brosnan ME (1982) Dietary protein, metabolic acidosis, and calcium balance. In: Draper HH, ed. Advances in Nutritional Research. New York: Plenum Press, pp. 77–105.Google Scholar
  20. 20.
    Portale AA, Halloran BP, Harris ST, Bikle DD, Morris RC, Jr (1992) Metabolic acidosis reverses the increase in serum 1,25 (OH)2D in phosphorus-restricted normal men. Am J Physiol 263: E1164–E1170.Google Scholar
  21. 21.
    Giovannucci E, Rimm EB, Wolk A, et al. (1998) Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 58: 442–447.Google Scholar
  22. 22.
    Chan JM, Giovannucci E, Andersson S-O, Yuen J, Adami H-O, Wolk A (1998) Dairy products, calcium, phosphorus, vitamin D, and risk of prostate cancer. Cancer Causes Control 9: 559–566.Google Scholar
  23. 23.
    Schuurman AG, van den Brandt PA, Dorant E, Goldbohm RA (1999) Animal products, calcum, and protein and prostate cancer risk in the Netherlands Cohort Study. Br J Cancer 80: 1107–1113.Google Scholar
  24. 24.
    Hayes RB, Ziegler RG, Gridley G, et al. (1999) Dietary factors and risk for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev 8: 25–34.Google Scholar
  25. 25.
    Ohno Y, Yoshida O, Oishi K, Okada K, Yamabe H, Schroeder FH (1988) Dietary beta-carotene and cancer of the prostate: a case-control study in Kyoto, Japan. Cancer Res 48: 1331–1336.Google Scholar
  26. 26.
    Vlajinac HD, Marinkovic JM, Ilic MD, Kocev NI (1997) Diet and prostate cancer: a case-control study. Eur J Cancer 33: 101–107.Google Scholar
  27. 27.
    Kristal AR, Stanford JL, Cohen JH, Wicklund K, Patterson RE (1999) Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 8: 887–892.Google Scholar
  28. 28.
    The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group (1994) The Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study: design, methods, participant characteristics, and compliance. Ann Epidemiol 4: 1–10.Google Scholar
  29. 29.
    The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330: 1029–1035.Google Scholar
  30. 30.
    Pietinen P, Hartman AM, Haapa E, et al. (1988) Reproducibility and validity of dietary assessment instruments. I. A self-adminis-tered food use questionnaire with a portion size picture booklet. Am J Epidemiol 128: 655–666.Google Scholar
  31. 31.
    Beahrs OH, Henson DE, Hutter RV, Kennedy BS, eds. American Joint Committee on Cancer (1992). Manual for Staging of Cancer, 4th edn. Philadelphia, PA: Lippincott, 1992.Google Scholar
  32. 32.
    Willett WC (1998) Nutritional Epidemiology, 2nd edn. New York: Oxford University Press.Google Scholar
  33. 33.
    Heinonen OP, Albanes D, Virtamo J, et al. (1998) Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90: 440–446.Google Scholar
  34. 34.
    Knochel JP (1999) Phosphorus. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th edn. Baltimore, MD: Williams & Wilkins, pp. 157–167.Google Scholar
  35. 35.
    Weaver CM, Heaney RP (1999) Calcium. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th edn. Baltimore, MD: Williams & Wilkins, pp. 141–155.Google Scholar
  36. 36.
    Schwartz GG, Hill CC, Oeler TA, Becich MJ, Bahnson RR (1995) 1,25–Dihydroxy-16–ene-23–yne-vitamin D3 and prostate cancer cell proliferation in vivo. Urology 46: 365–369.Google Scholar
  37. 37.
    Schwartz GG, Oeler TA, Uskokovic MR, Bahnson RR (1994) Human prostate cancer cells: inhibition of proliferation by vitamin D analogs. Anticancer Res 14: 1077–1081.Google Scholar
  38. 38.
    Skowronski RJ, Peehl DM, Feldman D (1995) Actions of vitamin D3 analogs on human prostate cancer cell lines: comparison with 1,25–dihydroxyvitamin D3. Endocrinology 136: 20–26.Google Scholar
  39. 39.
    Schwartz GG, Wang M-H, Zhang M, Singh RK, Siegal GP (1997) 1a,25–Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 6: 727–732.Google Scholar
  40. 40.
    Lucia MS, Anzano MA, Slayter MV, et al. (1995) Chemopreven-tive activity of tamoxifen, N-(4–hydroxyphenyl)retinamide, and the vitamin D analogue Ro24–5531 for androgen-promoted carcino-mas of the rat seminal vesicle and prostate. Cancer Res 55: 5621–5627.Google Scholar
  41. 41.
    Lokeshwar BL, Schwartz GG, Selzer MG, et al. (1999) Inhibition of prostate cancer metastases in vivo: a comparison of 1,25–dihydroxyvitamin D (calcitriol) and EB 1089. Cancer Epidemiol Biomarkers Prev 8: 241–248.Google Scholar
  42. 42.
    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: 235–239.Google Scholar
  43. 43.
    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: 121–126.Google Scholar
  44. 44.
    Corder EH, Guess HA, Hulka BS, et al. (1993) Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 2: 467–472.Google Scholar
  45. 45.
    Nomura AMY, Stemmermann GN, Lee J, et al. (1998) Serum vitamin D metabolite levels and the subsequent development of prostate cancer. Cancer Causes Control 9: 425–432.Google Scholar
  46. 46.
    Adams ND, Gray RW, Lemann J, Jr (1979) The effects of oral CaCO3 loading and dietary calcium deprivation on plasma 1,25–dihydroxyvitamin D concentrations in healthy adults. J Clin Endocrinol Metab 48: 1008–1016.Google Scholar
  47. 47.
    Berne RM, Levy MN (1988) Endocrine regulation of calcium and phosphate metabolism. In: Berne RM, Levy MN, eds. Physiology, 2nd edn. St Louis, Mo: C. V. Mosby, pp. 875–894.Google Scholar
  48. 48.
    Linder MC, ed. (1985) Nutritional Biochemistry and Metabolism with Clinical Applications. New York: Elsevier.Google Scholar
  49. 49.
    Clinton SK, Giovannucci E (1998) Diet, nutrition, and prostate cancer. Annu Rev Nutr 18: 413–440.Google Scholar
  50. 50.
    Tzonou A, Signorello LB, Lagiou P, Wuu J, Trichopoulos D, Trichopoulou A (1999) Diet and cancer of the prostate: a case-control study in Greece. Int J Cancer 80: 704–708.Google Scholar
  51. 51.
    Deneo-Pellegrini H, De Stefani E, Ronco A, Mendilaharsu M (1999) Foods, nutrients and prostate cancer: a case-control study in Uraguay. Br J Cancer 80: 591–597.Google Scholar
  52. 52.
    Hsing AW, McLaughlin JK, Schuman LM, et al. (1990) Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study. Cancer Res 50: 6836–6840.Google Scholar
  53. 53.
    Hsing AW, McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF (1991) Tobacco use and prostate cancer: 26–year follow-up of US veterans. Am J Epidemiol 133: 437–441.Google Scholar
  54. 54.
    Coughlin SS, Neaton JD, Sengupta A (1996) Cigarette smoking as a predictor of death from prostate cancer in 348,874 men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol 143: 1002–1006.Google Scholar
  55. 55.
    Giovannucci E, Rimm EB, Ascherio A, et al. (1999) Smoking and risk of total and fatal prostate cancer in United States health professionals. Cancer Epidemiol Biomarkers Prev 8: 277–282.Google Scholar
  56. 56.
    Smith ER, Hagopian M (1981) Uptake and secretion of carcin-ogenic chemicals by the dog and rat prostate. In: Murphy GP, Sandberg AA, Karr JP, eds. The Prostate Cell: Structure and Function. New York: Alan R. Liss, pp. 131–163.Google Scholar
  57. 57.
    Navone NM, Troncoso P, Pisters LL, et al. (1993) p53 protein accumulation and gene mutation in the progression of human prostate carcinoma. J Natl Cancer Inst 85: 1657–1669.Google Scholar
  58. 58.
    Brookstein R, MacGrogan D, Hilsenbeck SG, Sharkey R, Allred DC (1993) p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res 53: 3369–3373.Google Scholar
  59. 59.
    Visakorpi T, Kallioniemi PO, Heikkinen A, Koivula T, Isola J (1992) Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst 84: 883–887.Google Scholar
  60. 60.
    Chi S-G, De Vere White RW, Meyers FJ, Siders DB, Lee F, Gumerlock PH (1994) p53 mutations in prostate cancer: frequent expressed transition mutations. J Natl Cancer Inst 86: 926–933.Google Scholar
  61. 61.
    Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Gio-vannucci EL (1999) Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 8: 893–899.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • June M. Chan
  • Pirjo Pietinen
  • Mikko Virtanen
  • Nea Malila
  • Joseph Tangrea
  • Demetrius Albanes
  • Jarmo Virtamo

There are no affiliations available

Personalised recommendations