Biological Trace Element Research

, Volume 172, Issue 1, pp 86–92 | Cite as

Cadmium Levels in Tissue and Plasma as a Risk Factor for Prostate Carcinoma: a Meta-Analysis

  • Liang Zhang
  • Yi ZhuEmail author
  • Rui Hao
  • Mengmeng Shao
  • Yunbo Luo


Cadmium is a heavy metal that has been suggested to be a carcinogen by evidence. A number of published studies have investigated the association between cadmium levels and prostate cancer, but the results were inconsistent. Thus, we conducted a meta-analysis to get a precise estimate of this subject. After a careful searching and screening, a total of 11 publications containing 14 separated studies were included. Based on a random-effect model, the pooled data showed that cadmium levels of prostate tissues (standard mean difference (SMD) = 3.17, 95 % confidence interval (CI) = 0.60–5.74, P < 0.05) and plasma (SMD = 4.07, 95 % CI = 2.01–6.13, P < 0.05) were significantly higher in prostate cancer patients than those in the healthy controls. No difference of hair and nail cadmium levels between the prostate cancer cases and the controls was found. The data suggested that cadmium exposure might exert an influence on the tumorigenesis of prostate tissues. Future investigations with large sample sizes are needed to verify the results.


Cadmium Levels Prostate carcinoma Risk Meta-analysis 


Compliance with Ethical Standard

Competing Interests

The authors declared that they have no competing interests.


  1. 1.
    Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A (2014) Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 38(4):329–338. doi: 10.1016/j.canep.2014.06.002 CrossRefPubMedGoogle Scholar
  2. 2.
    Sawada N, Inoue M, Iwasaki M, Sasazuki S, Yamaji T, Shimazu T, Tsugane S (2014) Alcohol and smoking and subsequent risk of prostate cancer in Japanese men: the Japan Public Health Center-based prospective study. Int J Cancer 134(4):971–978. doi: 10.1002/ijc.28423 CrossRefPubMedGoogle Scholar
  3. 3.
    Attard G, Parker C, Eeles RA, Schroder F, Tomlins SA, Tannock I, Drake CG, de Bono JS (2015) Prostate cancer. Lancet. doi: 10.1016/S0140-6736(14)61947-4 Google Scholar
  4. 4.
    Byers T, Sedjo RL (2015) Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms. Endocr Relat Cancer 22(3):R125–R134. doi: 10.1530/ERC-14-0580 CrossRefPubMedGoogle Scholar
  5. 5.
    Labbe DP, Zadra G, Ebot EM, Mucci LA, Kantoff PW, Loda M, Brown M (2014) Role of diet in prostate cancer: the epigenetic link. Oncogene. doi: 10.1038/onc.2014.422 PubMedCentralGoogle Scholar
  6. 6.
    Lin PH, Aronson W, Freedland SJ (2015) Nutrition, dietary interventions and prostate cancer: the latest evidence. BMC Med 13:3. doi: 10.1186/s12916-014-0234-y CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Navarro Silvera SA, Rohan TE (2007) Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control 18(1):7–27. doi: 10.1007/s10552-006-0057-z CrossRefPubMedGoogle Scholar
  8. 8.
    Gumulec J, Masarik M, Adam V, Eckschlager T, Provaznik I, Kizek R (2014) Serum and tissue zinc in epithelial malignancies: a meta-analysis. PLoS One 9(6), e99790. doi: 10.1371/journal.pone.0099790 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hurst R, Hooper L, Norat T, Lau R, Aune D, Greenwood DC, Vieira R, Collings R, Harvey LJ, Sterne JA, Beynon R, Savovic J, Fairweather-Tait SJ (2012) Selenium and prostate cancer: systematic review and meta-analysis. Am J Clin Nutr 96(1):111–122. doi: 10.3945/ajcn.111.033373 CrossRefPubMedGoogle Scholar
  10. 10.
    Fujishiro H, Yano Y, Takada Y, Tanihara M, Himeno S (2012) Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics Integr Biometal Sci 4(7):700–708. doi: 10.1039/c2mt20024d CrossRefGoogle Scholar
  11. 11.
    Koedrith P, Kim H, Weon JI, Seo YR (2013) Toxicogenomic approaches for understanding molecular mechanisms of heavy metal mutagenicity and carcinogenicity. Int J Hyg Environ Health 216(5):587–598. doi: 10.1016/j.ijheh.2013.02.010 CrossRefPubMedGoogle Scholar
  12. 12.
    Feki-Tounsi M, Hamza-Chaffai A (2014) Cadmium as a possible cause of bladder cancer: a review of accumulated evidence. Environ Sci Pollut Res Int 21(18):10561–10573. doi: 10.1007/s11356-014-2970-0 CrossRefPubMedGoogle Scholar
  13. 13.
    Luckett BG, Su LJ, Rood JC, Fontham ET (2012) Cadmium exposure and pancreatic cancer in south Louisiana. J Environ Public Health 2012:180186. doi: 10.1155/2012/180186 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Demir N, Turksoy VA, Kayaalti Z, Soylemezoglu T, Savas I (2014) The evaluation of arsenic and cadmium levels in biological samples of cases with lung cancer. Tuberkuloz ve toraks 62(3):191–198PubMedGoogle Scholar
  15. 15.
    Stang A (2010) Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. doi: 10.1007/s10654-010-9491-z CrossRefPubMedGoogle Scholar
  16. 16.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748PubMedGoogle Scholar
  17. 17.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMedGoogle Scholar
  18. 18.
    Munafo MR, Clark TG, Flint J (2004) Assessing publication bias in genetic association studies: evidence from a recent meta-analysis. Psychiatry Res 129(1):39–44. doi: 10.1016/j.psychres.2004.06.011 CrossRefPubMedGoogle Scholar
  19. 19.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Luevano J, Damodaran C (2014) A review of molecular events of cadmium-induced carcinogenesis. J Environ Pathol Toxicol Oncol 33(3):183–194CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sahmoun AE, Case LD, Jackson SA, Schwartz GG (2005) Cadmium and prostate cancer: a critical epidemiologic analysis. Cancer Investig 23(3):256–263CrossRefGoogle Scholar
  22. 22.
    Verougstraete V, Lison D, Hotz P (2003) Cadmium, lung and prostate cancer: a systematic review of recent epidemiological data. J Toxicol Environ Health B Crit Rev 6(3):227–255. doi: 10.1080/10937400306465 CrossRefPubMedGoogle Scholar
  23. 23.
    Guzel S, Kiziler L, Aydemir B, Alici B, Ataus S, Aksu A, Durak H (2012) Association of Pb, Cd, and Se concentrations and oxidative damage-related markers in different grades of prostate carcinoma. Biol Trace Elem Res 145(1):23–32. doi: 10.1007/s12011-011-9162-2 CrossRefPubMedGoogle Scholar
  24. 24.
    Lee JD, Wu SM, Lu LY, Yang YT, Jeng SY (2009) Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans. J Formos Med Assoc 108(7):554–559. doi: 10.1016/s0929-6646(09)60373-9 CrossRefPubMedGoogle Scholar
  25. 25.
    Anetor JI, Ajose F, Anetor GO, Iyanda AA, Babalola OO, Adeniyi FA (2008) High cadmium/zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer. Niger J Phys Sci 23(1–2):41–49Google Scholar
  26. 26.
    Gray MA, Centeno JA, Slaney DP, Ejnik JW, Todorov T, Nacey JN (2005) Environmental exposure to trace elements and prostate cancer in three New Zealand ethnic groups. Int J Environ Res Public Health 2(3–4):374–384CrossRefPubMedGoogle Scholar
  27. 27.
    Armstrong BG, Kazantzis G (1985) Prostatic cancer and chronic respiratory and renal disease in British cadmium workers: a case control study. Br J Ind Med 42(8):540–545PubMedPubMedCentralGoogle Scholar
  28. 28.
    Bako G, Smith ES, Hanson J, Dewar R, Hill GB (1981) Cadmium and prostatic cancer in Alberta. Can Med Assoc J 124(2):121PubMedPubMedCentralGoogle Scholar
  29. 29.
    Chen YC, Pu YS, Wu HC, Wu TT, Lai MK, Yang CY, Sung FC (2009) Cadmium burden and the risk and phenotype of prostate cancer. BMC Cancer 9:429. doi: 10.1186/1471-2407-9-429 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Elghany NA, Schumacher MC, Slattery ML, West DW, Lee JS (1990) Occupation, cadmium exposure, and prostate cancer. Epidemiology (Cambridge, Mass) 1(2):107–115CrossRefGoogle Scholar
  31. 31.
    Eriksen KT, Halkjaer J, Meliker JR, McElroy JA, Sorensen M, Tjonneland A, Raaschou-Nielsen O (2015) Dietary cadmium intake and risk of prostate cancer: a Danish prospective cohort study. BMC Cancer 15:177. doi: 10.1186/s12885-015-1153-9 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Julin B, Wolk A, Johansson JE, Andersson SO, Andren O, Akesson A (2012) Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study. Br J Cancer 107(5):895–900. doi: 10.1038/bjc.2012.311 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Neslund-Dudas C, Mitra B, Kandegedara A, Chen D, Schmitt S, Shen M, Cui Q, Rybicki BA, Dou QP (2012) Association of metals and proteasome activity in erythrocytes of prostate cancer patients and controls. Biol Trace Elem Res 149(1):5–9. doi: 10.1007/s12011-012-9391-z CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sarafanov AG, Todorov TI, Centeno JA, Macias V, Gao W, Liang WM, Beam C, Gray MA, Kajdacsy-Balla AA (2011) Prostate cancer outcome and tissue levels of metal ions. Prostate 71(11):1231–1238. doi: 10.1002/pros.21339 CrossRefPubMedGoogle Scholar
  35. 35.
    Vinceti M, Venturelli M, Sighinolfi C, Trerotoli P, Bonvicini F, Ferrari A, Bianchi G, Serio G, Bergomi M, Vivoli G (2007) Case–control study of toenail cadmium and prostate cancer risk in Italy. Sci Total Environ 373(1):77–81. doi: 10.1016/j.scitotenv.2006.11.005 CrossRefPubMedGoogle Scholar
  36. 36.
    West DW, Slattery ML, Robison LM, French TK, Mahoney AW (1991) Adult dietary intake and prostate cancer risk in Utah: a case–control study with special emphasis on aggressive tumors. Cancer Causes Control 2(2):85–94CrossRefPubMedGoogle Scholar
  37. 37.
    van der Gulden JW, Kolk JJ, Verbeek AL (1995) Work environment and prostate cancer risk. Prostate 27(5):250–257CrossRefPubMedGoogle Scholar
  38. 38.
    Ouyang S, Li S (2000) Investigation of trace elements in hair of patients with prostate carcinoma, benign prostatic hypertrophy, and normal controls. Bull Hunan Med Univ 25 (3)Google Scholar
  39. 39.
    Qayyum MA, Shah MH (2014) Comparative study of trace elements in blood, scalp hair and nails of prostate cancer patients in relation to healthy donors. Biol Trace Elem Res 162(1–3):46–57. doi: 10.1007/s12011-014-0123-4 CrossRefPubMedGoogle Scholar
  40. 40.
    Platz EA, Helzlsouer KJ, Hoffman SC, Morris JS, Baskett CK, Comstock GW (2002) Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk. Prostate 52(4):288–296. doi: 10.1002/pros.10115 CrossRefPubMedGoogle Scholar
  41. 41.
    Brys M, Nawrocka AD, Miekos E, Zydek C, Foksinski M, Barecki A, Krajewska WM (1997) Zinc and cadmium analysis in human prostate neoplasms. Biol Trace Elem Res 59(1–3):145–152CrossRefPubMedGoogle Scholar
  42. 42.
    Feustel A, Wennrich R, Steiniger D, Klauss P (1982) Zinc and cadmium concentration in prostatic carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH). Urol Res 10(6):301–303CrossRefPubMedGoogle Scholar
  43. 43.
    Feustel A, Wennrich R, Dittrich H (1987) Zinc, cadmium and selenium concentrations in separated epithelium and stroma from prostatic tissues of different histology. Urol Res 15(3):161–163CrossRefPubMedGoogle Scholar
  44. 44.
    Lahtonen R (1985) Zinc and cadmium concentrations in whole tissue and in separated epithelium and stroma from human benign prostatic hypertrophic glands. Prostate 6(2):177–183CrossRefPubMedGoogle Scholar
  45. 45.
    Ogunlewe JO, Osegbe DN (1989) Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic, and malignant prostate. Cancer 63(7):1388–1392CrossRefPubMedGoogle Scholar
  46. 46.
    Feustel A, Wennrich R (1986) Zinc and cadmium plasma and erythrocyte levels in prostatic carcinoma, BPH, urological malignancies, and inflammations. Prostate 8(1):75–79CrossRefPubMedGoogle Scholar
  47. 47.
    Habib FK, Hammond GL, Lee IR, Dawson JB, Mason MK, Smith PH, Stitch SR (1976) Metal-androgen interrelationships in carcinoma and hyperplasia of the human prostate. J Endocrinol 71(1):133–141CrossRefPubMedGoogle Scholar
  48. 48.
    Chen G, Wu L, Wu Y, Zhu J (2015) Content change of zinc and cadmium in serum of patients with prostate cancer and its clinical significance. J Clin Urol (China) 30(5):439–441Google Scholar
  49. 49.
    Caciari T, Sancini A, Fioravanti M, Capozzella A, Casale T, Montuori L, Fiaschetti M, Schifano MP, Andreozzi G, Nardone N, Tomei G, Ciarrocca M, Rosati MV, Tomei F (2013) Cadmium and hypertension in exposed workers: a meta-analysis. Int J Occup Med Environ Health 26(3):440–456. doi: 10.2478/s13382-013-0111-5 CrossRefPubMedGoogle Scholar
  50. 50.
    Rodriguez-Barranco M, Lacasana M, Aguilar-Garduno C, Alguacil J, Gil F, Gonzalez-Alzaga B, Rojas-Garcia A (2013) Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: a systematic review and meta-analysis. Sci Total Environ 454–455:562–577. doi: 10.1016/j.scitotenv.2013.03.047 CrossRefPubMedGoogle Scholar
  51. 51.
    Schwartz GG, Reis IM (2000) Is cadmium a cause of human pancreatic cancer? Cancer Epidemiol Biomarkers Prev 9(2):139–145PubMedGoogle Scholar
  52. 52.
    Rahim F, Jalali A, Tangestani R (2013) Breast cancer frequency and exposure to cadmium: a meta-analysis and systematic review. Asian Pac J Cancer Prev 14(7):4283–4287CrossRefPubMedGoogle Scholar
  53. 53.
    Nawrot TS, Martens DS, Hara A, Plusquin M, Vangronsveld J, Roels HA, Staessen JA (2015) Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence. Cancer Causes Control. doi: 10.1007/s10552-015-0621-5 PubMedGoogle Scholar
  54. 54.
    Larsson SC, Wolk A (2015) Urinary cadmium and mortality from all causes, cancer and cardiovascular disease in the general population: systematic review and meta-analysis of cohort studies. Int J Epidemiol. doi: 10.1093/ije/dyv086 PubMedGoogle Scholar
  55. 55.
    Oliveira H, Monteiro C, Pinho F, Pinho S, Ferreira de Oliveira JM, Santos C (2014) Cadmium-induced genotoxicity in human osteoblast-like cells. Mutat Res Genet Toxicol Environ Mutagen 775–776:38–47. doi: 10.1016/j.mrgentox.2014.10.002 CrossRefPubMedGoogle Scholar
  56. 56.
    Du X, Lan T, Yuan B, Chen J, Hu J, Ren W, Chen Z (2015) Cadmium-induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice. Environ Toxicol 30(6):683–692. doi: 10.1002/tox.21946 CrossRefPubMedGoogle Scholar
  57. 57.
    Haase H, Ober-Blobaum JL, Engelhardt G, Hebel S, Rink L (2010) Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation. Toxicol Lett 198(2):152–158. doi: 10.1016/j.toxlet.2010.06.010 CrossRefPubMedGoogle Scholar
  58. 58.
    Yang Z, Lv Y, Wang Y (2012) Meta-analysis shows strong positive association of the TNF-alpha gene with tumor stage in bladder cancer. Urol Int 89(3):337–341. doi: 10.1159/000341701 CrossRefPubMedGoogle Scholar
  59. 59.
    Filipic M (2012) Mechanisms of cadmium induced genomic instability. Mutat Res 733(1–2):69–77. doi: 10.1016/j.mrfmmm.2011.09.002 CrossRefPubMedGoogle Scholar
  60. 60.
    Bibi M, Hashmi MZ, Malik RN (2015) The level and distribution of heavy metals and changes in oxidative stress indices in humans from Lahore district. Pak Hum Exp Toxicol. doi: 10.1177/0960327115578063 Google Scholar
  61. 61.
    Tete N, Afonso E, Crini N, Drouhot S, Prudent AS, Scheifler R (2014) Hair as a noninvasive tool for risk assessment: do the concentrations of cadmium and lead in the hair of wood mice (Apodemus sylvaticus) reflect internal concentrations? Ecotoxicol Environ Saf 108:233–241. doi: 10.1016/j.ecoenv.2014.07.010 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Liang Zhang
    • 1
    • 2
  • Yi Zhu
    • 1
    Email author
  • Rui Hao
    • 1
  • Mengmeng Shao
    • 1
  • Yunbo Luo
    • 1
  1. 1.College of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijingChina
  2. 2.Institute of CancerXinqiao Hospital, Third Military Medical UniversityChongqingChina

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