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Pancreatic cancer risk and levels of trace elements
  1. André F S Amaral1,
  2. Miquel Porta2,3,
  3. Debra T Silverman4,
  4. Roger L Milne1,
  5. Manolis Kogevinas5,
  6. Nathaniel Rothman4,
  7. Kenneth P Cantor6,
  8. Brian P Jackson7,
  9. José A Pumarega2,3,
  10. Tomàs López2,3,
  11. Alfredo Carrato8,9,
  12. Luisa Guarner10,
  13. Francisco X Real11,12,
  14. Núria Malats1
  1. 1Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  2. 2Institut Municipal d'Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3CIBERESP, Barcelona, Spain
  4. 4Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  5. 5Centre de Recerca en Epidemiologia Ambiental, Barcelona, Spain
  6. 6KP Cantor Environmental LLC, Silver Spring, Maryland, USA
  7. 7Trace Element Analysis Core, Department of Earth Sciences, Dartmouth College, Hanover, New Hampshire, USA
  8. 8Hospital Ramón y Cajal, Madrid, Spain
  9. 9Hospital General de Elche, Alicante, Spain
  10. 10Hospital de la Vall Hebron, Barcelona, Spain
  11. 11Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  12. 12Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
  1. Correspondence to Dr Núria Malats, Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, 28029 Madrid, Spain; nuria{at}


Background and Aims Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk.

Methods The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression.

Results Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; ptrend=5×10−6), arsenic (OR 2.02, 95% CI 1.08 to 3.78; ptrend=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; ptrend=3×10−5) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; ptrend=8×10−11) and nickel (OR 0.27, 95% CI 0.12 to 0.59; ptrend=2×10−4) were inversely associated with the risk of EPC.

Conclusion Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

  • Arsenic
  • cadmium
  • cancer
  • epidemiology
  • epithelial differentiation
  • genetics
  • lead
  • molecular carcinogenesis
  • molecular epidemiology
  • molecular oncology
  • mucins
  • pancreas
  • pancreatic cancer
  • pancreatic epidemiology
  • pancreatic tumours
  • polymorphic variation
  • selenium
  • statistics

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  • Funding This work was partly supported by the Association for International Cancer Research (AICR09-0780), Fondo de Investigación Sanitaria, Spain (#PI09-02102), Red Temática de Investigación Cooperativa en Cáncer (RTICC) and CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Ministry of Health, Spain, Fundación Científica de la Asociación Española Contra el Cáncer (AECC) and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA. The Dartmouth Trace Element Core is partly supported by NIH grant number P42 ES007373 from the National Institute of Environmental Health Sciences.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was obtained from local institutional review boards.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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