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Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence

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Abstract

Background

Recent studies are indicative of substantial progress in understanding the dose–response relation between the incidence of total and lung cancer and environmental cadmium exposure. We conducted a meta-analysis of population studies that examined the risk of cancer in relation to lifetime exposure to cadmium.

Methods

We searched MEDLINE, Web of Science, and relevant reviews until August 2014 for studies on the association between cancer risk and cadmium exposure. Eligible studies had to include an estimate of lifetime exposure to cadmium as reflected by the urinary cadmium concentration and adjustment of the cancer risk at least for age and smoking. We pooled relative risk across the studies estimates for cancer and lung cancer using variance-weighted random-effect models and expressed association sizes for a twofold increase in urinary cadmium, thereby respecting the continuous nature of the association.

Results

The meta-analysis included 20,459 participants from three prospective population studies. The average urinary cadmium concentration across populations ranged from 0.25 to 0.93 µg/g creatinine. The relative risk of total cancer, associated with a doubling of the urinary cadmium concentration, ranged across the different studies from 1.18 to 1.31, and the pooled relative risk was 1.22 (95 % CI 1.13–1.31; p < 0.0001). For lung cancer, the relative risk ranged from 1.21 to 1.70 for a doubling of the urinary cadmium concentration, while the pooled relative risk amounted to 1.68 (1.47–1.92; p < 0.0001). Excluding one study at the time did not move the pooled estimates outside the confidence interval of the overall estimate for all studies combined.

Conclusion

The epidemiological evidence of the last decade consistently identifies low-level environmental exposure to cadmium as a risk factor for total cancer and lung cancer.

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References

  1. Jaworowski Z, Barbalat F, Blain C, Peyre E (1985) Heavy metals in human and animal bones from ancient and contemporary France. Sci Total Environ 43:103–126

    Article  CAS  PubMed  Google Scholar 

  2. Bernhard D, Rossmann A, Henderson B, Kind M, Seubert A, Wick G (2006) Increased serum cadmium and strontium levels in young smokers: effects on arterial endothelial cell gene transcription. Arterioscler Thromb Vasc Biol 26:833–838

    Article  CAS  PubMed  Google Scholar 

  3. Nawrot TS, Staessen JA, Roels HA, Munters E, Cuypers A, Richart T, Ruttens A, Smeets K, Clijsters H, Vangronsveld J (2010) Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 23:769–782

    Article  CAS  PubMed  Google Scholar 

  4. Nordberg GF, Kido T, Roels HA (2008) Cadmium-induced renal effects. In: De Broe ME, Porter GA (eds) Clinical nephrotoxins, 3rd edn. Springer Science, New York, pp 785–810

    Chapter  Google Scholar 

  5. Elder A, Nordberg GF, Kleinman M (2015) Routes of exposure, dose, and toxicokinetics of metals. In: Nordberg GF, Fowler BA, Nordberg M (eds) Handbook on toxicology of metals, 4th edn. Academic Press, London, pp 45–74

    Google Scholar 

  6. Nawrot TS, Kuenzli N, Sunyer J, Shi T, Moreno T, Viana M, Heinrich J, Forsberg B, Kelly FJ, Sughis M, Nemery B, Borm P (2009) Oxidative properties of ambient PM2.5 and elemental composition: heterogeneous associations in 19 European cities. Atmos Environ 43:4595–4602

    Article  CAS  Google Scholar 

  7. IARC (1993) Beryllium, cadmium, mercury and exposure in the glass manufacturing industry. Monographs on the evaluation of carcinogenic risks in humans, vol 58. International Agency for Research on Cancer, Lyon

  8. Nordberg GF, Herber RFM, Allessio G (1992) Cadmium in the human environment: toxicity and carcinogenicity. IARC scientific publications, Lyon

    Google Scholar 

  9. Nawrot T, Plusquin M, Hogervorst J, Roels HA, Celis H, Thijs L, Vangronsveld J, Van Hecke E, Staessen JA (2006) Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 7:119–126

    Article  CAS  PubMed  Google Scholar 

  10. Adams SV, Passarelli MN, Newcomb PA (2012) Cadmium exposure and cancer mortality in the third national health and nutrition examination survey cohort. Occup Environ Med 69:153–156

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Cheung MR, Kang J, Ouyang D, Yeung V (2014) Association between urinary cadmium and all cause, all cancer and prostate cancer specific mortalities for men: an analysis of national health and nutrition examination survey (NHANES III) data. Asian Pac J Cancer Prev 15:483–488

    Article  PubMed  Google Scholar 

  12. Garcia-Esquinas E, Pollan M, Tellez-Plaza M, Francesconi KA, Goessler W, Guallar E, Umans JG, Yeh J, Best LG, Navas-Acien A (2014) Cadmium exposure and cancer mortality in a prospective cohort: the strong heart study. Environ Health Perspect 122:363–370

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Lin YS, Caffrey JL, Lin JW, Bayliss D, Faramawi MF, Bateson TF, Sonawane B (2013) Increased risk of cancer mortality associated with cadmium exposures in older Americans with low zinc intake. J Toxicol Environ Health A 76:1–15

    Article  CAS  PubMed  Google Scholar 

  14. Menke A, Muntner P, Silbergeld EK, Platz EA, Guallar E (2009) Cadmium levels in urine and mortality among U.S. adults. Environ Health Perspect 117:190–196

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  16. Nawrot TS, Van Hecke E, Thijs L, Richart T, Kuznetsova T, Jin Y, Vangronsveld J, Roels HA, Staessen JA (2008) Cadmium-related mortality and long-term secular trends in the cadmium body burden of an environmentally exposed population. Environ Health Perspect 116:1620–1628

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. 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 6:227–255

    Article  CAS  PubMed  Google Scholar 

  18. Jarup L, Bellander T, Hogstedt C, Spang G (1998) Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel. Occup Environ Med 55:755–759

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kazantzis G, Blanks RG, Sullivan KR (1992) Is cadmium a human carcinogen? IARC Sci Publ 118:435–446

  20. Sorahan T, Lancashire RJ (1997) Lung cancer mortality in a cohort of workers employed at a cadmium recovery plant in the United States: an analysis with detailed job histories. Occup Environ Med 54:194–201

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Sorahan T, Waterhouse JA (1983) Mortality study of nickel-cadmium battery workers by the method of regression models in life tables. Br J Ind Med 40:293–300

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Sorahan T, Lister A, Gilthorpe MS, Harrington JM (1995) Mortality of copper cadmium alloy workers with special reference to lung cancer and non-malignant diseases of the respiratory system, 1946–92. Occup Environ Med 52:804–812

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Hartwig A (2010) Mechanisms in cadmium-induced carcinogenicity: recent insights. Biometals 23:951–960

    Article  CAS  PubMed  Google Scholar 

  24. Thevenod F, Lee WK (2013) Toxicology of cadmium and its damage to mammalian organs. Met Ions Life Sci 11:415–490

    Article  CAS  PubMed  Google Scholar 

  25. Watkin RD, Nawrot T, Potts RJ, Hart BA (2003) Mechanisms regulating the cadmium-mediated suppression of Sp1 transcription factor activity in alveolar epithelial cells. Toxicology 184:157–178

    Article  CAS  PubMed  Google Scholar 

  26. Jin YH, Clark AB, Slebos RJ, Al-Refai H, Taylor JA, Kunkel TA, Resnick MA, Gordenin DA (2003) Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet 34:326–329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Martinez-Zamudio R, Ha HC (2011) Environmental epigenetics in metal exposure. Epigenetics 6:820–827

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Arisawa K, Nakano A, Saito H, Liu XJ, Yokoo M, Soda M, Koba T, Takahashi T, Kinoshita K (2001) Mortality and cancer incidence among a population previously exposed to environmental cadmium. Int Arch Occup Environ Health 74:255–262

    Article  CAS  PubMed  Google Scholar 

  29. Arisawa K, Uemura H, Hiyoshi M, Dakeshita S, Kitayama A, Saito H, Soda M (2007) Cause-specific mortality and cancer incidence rates in relation to urinary beta2-microglobulin: 23-year follow-up study in a cadmium-polluted area. Toxicol Lett 173:168–174

    Article  CAS  PubMed  Google Scholar 

  30. Li Q, Nishijo M, Nakagawa H, Morikawa Y, Sakurai M, Nakamura K, Kido T, Nogawa K, Dai M (2011) Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area: a 22-year follow-up study in Japan. Chin Med J (Engl) 124:3504–3509

    CAS  Google Scholar 

  31. Nakagawa H, Nishijo M, Morikawa Y, Miura K, Tawara K, Kuriwaki J, Kido T, Ikawa A, Kobayashi E, Nogawa K (2006) Urinary cadmium and mortality among inhabitants of a cadmium-polluted area in Japan. Environ Res 100:323–329

    Article  CAS  PubMed  Google Scholar 

  32. Nishijo M, Morikawa Y, Nakagawa H, Tawara K, Miura K, Kido T, Ikawa A, Kobayashi E, Nogawa K (2006) Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment. Occup Environ Med 63:545–550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Jarup L, Berglund M, Elinder CG, Nordberg G, Vahter M (1998) Health effects of cadmium exposure—a review of the literature and a risk estimate. Scand J Work Environ Health 24(Suppl 1):1–51

    PubMed  Google Scholar 

  34. Axelson O, Steenland K (1988) Indirect methods of assessing the effects of tobacco use in occupational studies. Am J Ind Med 13:105–118

    Article  CAS  PubMed  Google Scholar 

  35. Blair A, Hoar SK, Walrath J (1985) Comparison of crude and smoking-adjusted standardized mortality ratios. J Occup Med 27:881–884

    CAS  PubMed  Google Scholar 

  36. Siemiatycki J, Wacholder S, Dewar R, Cardis E, Greenwood C, Richardson L (1988) Degree of confounding bias related to smoking, ethnic group, and socioeconomic status in estimates of the associations between occupation and cancer. J Occup Med 30:617–625

    Article  CAS  PubMed  Google Scholar 

  37. Staessen J, Amery A, Bernard A, Bruaux P, Buchet JP, Bulpitt CJ, Claeys F, De Plaen P, Ducoffre G, Fagard R, et al (1991) Blood pressure, the prevalence of cardiovascular diseases, and exposure to cadmium: a population study. Am J Epidemiol 134:257-267

    Article  CAS  PubMed  Google Scholar 

  38. Vahter M, Akesson A, Liden C, Ceccatelli S, Berglund M (2007) Gender differences in the disposition and toxicity of metals. Environ Res 104:85–95

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by grants from the European Research Council (ERC-2012-StG 310898) and Flemish Research Council (FWO G073315N/G.0880.13). We thank Dr. García-Esquinas and Dr. Navas-Ancien for providing necessary input of their study to make comparison on a continuous scale possible.

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Authors and Affiliations

  1. Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium

    Tim S. Nawrot, Dries S. Martens, Michelle Plusquin, Jaco Vangronsveld & Harry A. Roels

  2. Department of Public Health, Leuven University, Louvain, Belgium

    Tim S. Nawrot

  3. KU Leuven Department of Cardiovascular Sciences, Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Louvain, Belgium

    Azusa Hara & Jan A. Staessen

  4. VitaK Research and Development, Maastricht University, Maastricht, The Netherlands

    Jan A. Staessen

  5. Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium

    Harry A. Roels

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  1. Tim S. Nawrot
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Correspondence to Tim S. Nawrot.

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Nawrot, T.S., Martens, D.S., Hara, A. et al. Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence. Cancer Causes Control 26, 1281–1288 (2015). https://doi.org/10.1007/s10552-015-0621-5

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  • DOI: https://doi.org/10.1007/s10552-015-0621-5

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