Cancer Causes & Control

, 22:1483 | Cite as

Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection among US men

  • Hind A. Beydoun
  • Monal R. Shroff
  • Ravinder Mohan
  • May A. Beydoun
Original paper


Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection were evaluated among 3,927 US men, 40–85 years of age, who participated in the 2001–2006 National Health and Nutrition Examination Surveys. Five recommended definitions of prostate cancer detection were adopted using total and free prostate-specific antigen (tPSA and fPSA) laboratory measurements. Men were identified as high risk based on alternative cutoffs, namely tPSA > 10 ng/ml, tPSA > 4 ng/ml, tPSA > 2.5 ng/ml, %fPSA < 25%, and %fPSA < 15%. %fPSA was defined as (fPSA÷tPSA)× 100%. Serum levels of vitamin A (retinol and retinyl esters) and carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein + zeaxanthin, lycopene) were defined as quartiles and examined as risk/protective factors for PSA biomarkers. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using binary logistic models. After adjustment for known demographic, socioeconomic, and lifestyle confounders, high serum levels of retinyl esters (tPSA > 10 ng/ml: Q4 vs. Q1 → OR = 0.38, 95% CI: 0.14–1.00) and α-carotene (%fPSA < 15%: Q4 vs. Q1 → OR = 0.49, 95% CI: 0.32–0.76) were associated with a lower odds, whereas high serum level of lycopene (tPSA > 2.5 ng/ml: Q4 vs. Q1 → OR = 1.49, 95% CI: 1.01–2.14) was associated with a greater odds of prostate cancer detection. Apart from the three significant associations observed, no other exposure–outcome association was significant. Monitoring specific antioxidant levels may be helpful in the early detection of prostate cancer.


Vitamin A Carotenoids Prostate cancer Prostate-specific antigen 



Body mass index


Confidence interval


Digital rectal exam


Free prostate-specific antigen


Percent free prostate-specific antigen


First quartile


Second quartile


Third quartile


Fourth quartile


National Health and Nutrition Examination Survey


Odds ratio


Prostate cancer


Prostate-specific antigen


Reactive oxygen species


Total prostate-specific antigen



This research was partly supported by the Intramural Research Program of the NIH, National Institute on Aging. We would like to thank Dr. Larry Brant and Dr. Joshua Goh for providing useful comments regarding the content of the manuscript.


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300PubMedCrossRefGoogle Scholar
  2. 2.
    Culp S, Porter M (2009) The effect of obesity and lower serum prostate-specific antigen levels on prostate-cancer screening results in American men. BJU Int 104(10):1457–1461PubMedCrossRefGoogle Scholar
  3. 3.
    Hegarty NJ, Fitzpatrick JM, Richie JP, Scardino PT, deVere White RW, Schroder FH et al (1999) Future prospects in prostate cancer. Prostate 40(4):261–268PubMedCrossRefGoogle Scholar
  4. 4.
    Calonge N, Petitti DB, DeWitt TG, Dietrich AJ, Gregory KD, Harris R, Isham GJ, LeFevre ML, Leipzig R, Loveland-Cherry C, Marion LN, Melnyk B, Moyer VA, Ockene JK, Sawaya GF, Yawn BP (2008) Screening for prostate cancer: US. Preventive services task force recommendation statement. Ann Intern Med 149(3):185–191Google Scholar
  5. 5.
    Lacher DA, Thompson TD, Hughes JP, Saraiya M (2006) Total, free, and percent free prostate-specific antigen levels among US men, 2001–2004. Adv Data 4(379):1–12Google Scholar
  6. 6.
    Saraiya M, Kottiri BJ, Leadbetter S, Blackman D, Thompson T, McKenna MT et al (2005) Total and percent free prostate-specific antigen levels among US men, 2001–2002. Cancer Epidemiol Biomarkers Prev 14(9):2178–2182PubMedCrossRefGoogle Scholar
  7. 7.
    Singer EA, Palapattu GS, van Wijngaarden E (2008) Prostate-specific antigen levels in relation to consumption of nonsteroidal anti-inflammatory drugs and acetaminophen: results from the 2001–2002 National Health and Nutrition Examination Survey. Cancer 113(8):2053–2057PubMedCrossRefGoogle Scholar
  8. 8.
    Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J et al (2004) Human prostate cancer risk factors. Cancer 101(10 Suppl):2371–2490PubMedCrossRefGoogle Scholar
  9. 9.
    Boyle P, Severi G, Giles GG (2003) The epidemiology of prostate cancer. Urol Clin North Am 30(2):209–217PubMedCrossRefGoogle Scholar
  10. 10.
    Gallagher RP, Fleshner N (1998) Prostate cancer: 3. Individual risk factors. CMAJ 159(7):807–813PubMedGoogle Scholar
  11. 11.
    Gronberg H (2003) Prostate cancer epidemiology. Lancet 361(9360):859–864PubMedCrossRefGoogle Scholar
  12. 12.
    Hsing AW, Devesa SS (2001) Trends and patterns of prostate cancer: what do they suggest? Epidemiol Rev 23(1):3–13PubMedGoogle Scholar
  13. 13.
    Levy IG, Iscoe NA, Klotz LH (1998) Prostate cancer: 1. The descriptive epidemiology in Canada. CMAJ 159(5):509–513PubMedGoogle Scholar
  14. 14.
    Routh JC, Leibovich BC (2005) Adenocarcinoma of the prostate: epidemiological trends, screening, diagnosis, and surgical management of localized disease. Mayo Clin Proc 80(7):899–907PubMedCrossRefGoogle Scholar
  15. 15.
    Stotts RC (2004) Cancers of the prostate, penis, and testicles: epidemiology, prevention, and treatment. Nurs Clin North Am 39(2):327–340PubMedCrossRefGoogle Scholar
  16. 16.
    Hsing AW, Chokkalingam AP (2006) Prostate cancer epidemiology. Front Biosci 11:1388–1413PubMedCrossRefGoogle Scholar
  17. 17.
    Nelson WG, De Marzo AM, Isaacs WB (2003) Prostate cancer. N Engl J Med 349(4):366–381PubMedCrossRefGoogle Scholar
  18. 18.
    De Marzo AM, DeWeese TL, Platz EA, Meeker AK, Nakayama M, Epstein JI et al (2004) Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment. J Cell Biochem 91(3):459–477PubMedCrossRefGoogle Scholar
  19. 19.
    Platz EA, De Marzo AM (2004) Epidemiology of inflammation and prostate cancer. J Urol 171(2 Pt 2):S36–S40PubMedCrossRefGoogle Scholar
  20. 20.
    De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG et al (2007) Inflammation in prostate carcinogenesis. Nat Rev Cancer 7(4):256–269PubMedCrossRefGoogle Scholar
  21. 21.
    Adami H-O, Hunter D, Trichopoulos D (2008) Textbook of cancer epidemiology, 2nd edn. Oxford University Press, New YorkCrossRefGoogle Scholar
  22. 22.
    Parekh N, Lin Y, Dipaola RS, Marcella S, Lu-Yao G (2010) Obesity and prostate cancer detection: insights from three national surveys. Am J Med 123(9):829–835PubMedCrossRefGoogle Scholar
  23. 23.
    Parekh N, Lin Y, Marcella S, Kant AK, Lu-Yao G (2008) Associations of lifestyle and physiologic factors with prostate-specific antigen concentrations: evidence from the National Health and Nutrition Examination Survey (2001–2004). Cancer Epidemiol Biomarkers Prev 17(9):2467–2472PubMedCrossRefGoogle Scholar
  24. 24.
    Joseph DA, Thompson T, Saraiya M, Werny DM. (2009) Association between glomerular filtration rate, free, total, and percent free prostate-specific antigen. UrologyGoogle Scholar
  25. 25.
    Mondul AM, Selvin E, De Marzo AM, Freedland SJ, Platz EA (2010) Statin drugs, serum cholesterol, and prostate-specific antigen in the National Health and Nutrition Examination Survey 2001–2004. Cancer Causes Control 21(5):671–678PubMedCrossRefGoogle Scholar
  26. 26.
    Chang SL, Harshman LC, Presti JC Jr (2010) Impact of common medications on serum total prostate-specific antigen levels: analysis of the National Health and Nutrition Examination Survey. J Clin Oncol 28(25):3951–3957PubMedCrossRefGoogle Scholar
  27. 27.
    Werny DM, Saraiya M, Gregg EW (2006) Prostate-specific antigen values in diabetic and nondiabetic US men, 2001–2002. Am J Epidemiol 164(10):978–983PubMedCrossRefGoogle Scholar
  28. 28.
    Royston P, Sauerbrei W (2009) Multivariable model-building: a pragmatic approach to regression analysis based on fractional polynomials for modelling continuous variables. Wiley, HobokenGoogle Scholar
  29. 29.
    Wagenlehner FM, Elkahwaji JE, Algaba F, Bjerklund-Johansen T, Naber KG, Hartung R et al (2007) The role of inflammation and infection in the pathogenesis of prostate carcinoma. BJU Int 100(4):733–737PubMedCrossRefGoogle Scholar
  30. 30.
    Carotenoid. Available from:
  31. 31.
    Basu A, Imrhan V (2007) Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. Eur J Clin Nutr 61(3):295–303PubMedCrossRefGoogle Scholar
  32. 32.
    Edinger MS, Koff WJ (2006) Effect of the consumption of tomato paste on plasma prostate-specific antigen levels in patients with benign prostate hyperplasia. Braz J Med Biol Res 39(8):1115–1119PubMedCrossRefGoogle Scholar
  33. 33.
    Haseen F, Cantwell MM, O’Sullivan JM, Murray LJ (2009) Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review. Prostate Cancer Prostatic Dis 12(4):325–332PubMedCrossRefGoogle Scholar
  34. 34.
    Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F et al (2002) Effects of lycopene supplementation in patients with localized prostate cancer. Exp Biol Med (Maywood) 227(10):881–885Google Scholar
  35. 35.
    Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F et al (2001) Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 10(8):861–868PubMedGoogle Scholar
  36. 36.
    Liu A, Pajkovic N, Pang Y, Zhu D, Calamini B, Mesecar AL et al (2006) Absorption and subcellular localization of lycopene in human prostate cancer cells. Mol Cancer Ther 5(11):2879–2885PubMedCrossRefGoogle Scholar
  37. 37.
    Rao AV, Fleshner N, Agarwal S (1999) Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer 33(2):159–164PubMedCrossRefGoogle Scholar
  38. 38.
    Schroder FH, Roobol MJ, Boeve ER, de Mutsert R, Zuijdgeest-van Leeuwen SD, Kersten I et al (2005) Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement. Eur Urol 48(6):922–930 (discussion 30-1)Google Scholar
  39. 39.
    Schwarz S, Obermuller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK (2008) Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr 138(1):49–53PubMedGoogle Scholar
  40. 40.
    Stacewicz-Sapuntzakis M, Bowen PE (2005) Role of lycopene and tomato products in prostate health. Biochim Biophys Acta 1740(2):202–205PubMedGoogle Scholar
  41. 41.
    Talvas J, Caris-Veyrat C, Guy L, Rambeau M, Lyan B, Minet-Quinard R et al (2010) Differential effects of lycopene consumed in tomato paste and lycopene in the form of a purified extract on target genes of cancer prostatic cells. Am J Clin Nutr 91(6):1716–1724PubMedCrossRefGoogle Scholar
  42. 42.
    Vaishampayan U, Hussain M, Banerjee M, Seren S, Sarkar FH, Fontana J et al (2007) Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer 59(1):1–7PubMedCrossRefGoogle Scholar
  43. 43.
    Etminan M, Takkouche B, Caamano-Isorna F (2004) The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev 13(3):340–345PubMedGoogle Scholar
  44. 44.
    Erdman JW Jr, Ford NA, Lindshield BL (2009) Are the health attributes of lycopene related to its antioxidant function? Arch Biochem Biophys 483(2):229–235PubMedCrossRefGoogle Scholar
  45. 45.
    Lung cancer associated with beta-carotene supplementation in smokers. Prescrire Int 19(107):121Google Scholar
  46. 46.
    Kim Y, Chongviriyaphan N, Liu C, Russell RM, Wang XD (2006) Combined antioxidant (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation increases the levels of lung retinoic acid and inhibits the activation of mitogen-activated protein kinase in the ferret lung cancer model. Carcinogenesis 27(7):1410–1419PubMedCrossRefGoogle Scholar
  47. 47.
    Kim Y, Lian F, Yeum KJ, Chongviriyaphan N, Choi SW, Russell RM et al (2007) The effects of combined antioxidant (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single-strand breaks and levels of insulin-like growth factor-1/IGF-binding protein 3 in the ferret model of lung cancer. Int J Cancer 120(9):1847–1854PubMedCrossRefGoogle Scholar
  48. 48.
    Greenwald P (2003) Beta-carotene and lung cancer: a lesson for future chemoprevention investigations? J Natl Cancer Inst 95(1):E1PubMedCrossRefGoogle Scholar
  49. 49.
    Holick CN, Michaud DS, Stolzenberg-Solomon R, Mayne ST, Pietinen P, Taylor PR et al (2002) Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study. Am J Epidemiol 156(6):536–547PubMedCrossRefGoogle Scholar
  50. 50.
    Neuhouser ML, Patterson RE, Thornquist MD, Omenn GS, King IB, Goodman GE (2003) Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Cancer Epidemiol Biomarkers Prev 12(4):350–358PubMedGoogle Scholar
  51. 51.
    Satia JA, Littman A, Slatore CG, Galanko JA, White E (2009) Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins and lifestyle (VITAL) study. Am J Epidemiol 169(7):815–828PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Hind A. Beydoun
    • 1
  • Monal R. Shroff
    • 2
  • Ravinder Mohan
    • 3
  • May A. Beydoun
    • 4
  1. 1.Graduate Program in Public HealthEastern Virginia Medical SchoolNorfolkUSA
  2. 2.Department of EpidemiologyUniversity of MichiganAnn ArborUSA
  3. 3.Department of Family MedicineEastern Virginia Medical SchoolNorfolkUSA
  4. 4.NIH/Intramural Research ProgramNational Institute on AgingBaltimoreUSA

Personalised recommendations