Skip to main content
Log in

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Background

Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs).

Objective

To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC).

Methods

Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids.

Results

Lower concentrations of six of the seven OCs analyzed (p,p′-DDE, three polychlorinated biphenyls, hexachlorobenzene, and β-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p′-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p′-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p′-DDE, p,p′-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage.

Conclusions

Restriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

β:

Regression coefficient

CI:

Confidence interval

p,p′-DDE:

Dichlorodiphenyldichloroethene or 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene

p,p-DDT:

Dichlorodiphenyltrichloroethane or (bis[p-chlorophenyl]-1,1,1-trichloroethane)

EPC:

Exocrine pancreatic cancer

GLM:

General linear models

HCB:

Hexachlorobenzene

HCH:

Hexachlorocyclohexane

IES:

Interval from blood extraction (or blood draw) to first symptom of EPC

OCs:

Organochlorine compounds

PCBs:

Polychlorinated biphenyls

R 2 :

Coefficient of determination

TSL:

Total serum lipids

References

  1. United Nations Environment Programme (UNEP), Global Environment Facility (GEF), Inter-Organization Programme for the Sound Management of Chemicals (IOMC) (2003) Regionally based assessment of persistent toxic substances. Global Report 2003. UNEP Chemicals, Châtelaine, Switzerland. Available from http://www.chem.unep.ch/pts/gr/Global_Report.pdf. Accessed 18 June 2009

  2. Alcock R, Bashkin V, Bisson M, et al Joint WHO/Convention Task Force on the Health Aspects of Air Pollution (2003) Health risks of persistent organic pollutants from long-range transboundary air pollution. World Health Organization, Regional Office for Europe, Copenhagen. Available from http://www.euro.who.int/Document/e78963.pdf. Accessed 18 June 2009

  3. Porta M, Puigdomènech E, Ballester F et al (2008) Monitoring concentrations of persistent organic pollutants in the general population: the international experience. Environ Int 34:546–561

    Article  CAS  PubMed  Google Scholar 

  4. Wolff MS, Anderson HA, Britton JA, Rothman N (2007) Pharmacokinetic variability and modern epidemiology—the example of dichlorodiphenyltrichloroethane, body mass index, and birth cohort. Cancer Epidemiol Biomarkers Prev 16:1925–1930

    Article  CAS  PubMed  Google Scholar 

  5. Schisterman EF, Whitcomb BW, Louis GM et al (2005) Lipid adjustment in the analysis of environmental contaminants and human health risks. Environ Health Perspect 113:853–857

    CAS  PubMed  Google Scholar 

  6. Porta M (2001) Role of organochlorine compounds in the etiology of pancreatic cancer: a proposal to develop methodological standards. Epidemiology 12:272–276

    Article  CAS  PubMed  Google Scholar 

  7. Porta M (ed) (2008) A dictionary of epidemiology, 5th edn. Oxford University Press, New York, p 69, 226

  8. Wolff MS, Zeleniuch-Jacquotte A, Dubin N, Toniolo P (2000) Risk of breast cancer and organochlorine exposure. Cancer Epidemiol Biomarkers Prev 9:271–277

    CAS  PubMed  Google Scholar 

  9. Hoppin JA, Tolbert PE, Holly EA et al (2000) Pancreatic cancer and serum organochlorine levels. Cancer Epidemiol Biomark Prev 9:199–205

    CAS  Google Scholar 

  10. Porta M, Malats N, Jariod M et al (1999) Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. Lancet 354:2125–2129

    Article  CAS  PubMed  Google Scholar 

  11. De Roos AJ, Hartge P, Lubin JH et al (2005) Persistent organochlorine chemicals in plasma and risk of non-Hodgkin’s lymphoma. Cancer Res 65:11214–11226

    Article  PubMed  CAS  Google Scholar 

  12. Vo TT, Gladen BC, Cooper GS et al (2008) Dichlorodiphenyldichloroethane and polychlorinated biphenyls: intraindividual changes, correlations, and predictors in healthy women from the southeastern United States. Cancer Epidemiol Biomarkers Prev 17:2729–2736

    Article  CAS  PubMed  Google Scholar 

  13. Baris D, Kwak LW, Rothman N et al (2000) Blood levels of organochlorines before and after chemotherapy among non-Hodgkin’s lymphoma patients. Cancer Epidemiol Biomarkers Prev 9:193–197

    CAS  PubMed  Google Scholar 

  14. Wolff MS, Toniolo PG, Lee EW et al (1993) Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst 85:648–652

    Article  CAS  PubMed  Google Scholar 

  15. Hunter DJ, Hankinson SE, Laden F et al (1997) Plasma organochlorine levels and the risk of breast cancer. N Engl J Med 337:1253–1258

    Article  CAS  PubMed  Google Scholar 

  16. Dorgan JF, Brock JW, Rothman N et al (1999) Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). Cancer Causes Control 10:1–11

    Article  CAS  PubMed  Google Scholar 

  17. Porta M, Fernandez E, Alguacil J (2003) Semiology, proteomics, and the early detection of symptomatic cancer. J Clin Epidemiol 56:815–819

    Article  PubMed  Google Scholar 

  18. Porta M, Fabregat X, Malats N et al (2005) Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol 7:189–197

    Article  PubMed  Google Scholar 

  19. Spinelli JJ, Ng CH, Weber JP et al (2007) Organochlorines and risk of non-Hodgkin lymphoma. Int J Cancer 121:2767–2775

    Article  CAS  PubMed  Google Scholar 

  20. McGlynn KA, Abnet CC, Zhang M et al (2006) Serum concentrations of 1, 1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and risk of primary liver cancer. J Natl Cancer Inst 98:1005–1010

    CAS  PubMed  Google Scholar 

  21. McGlynn KA, Quraishi SM, Graubard BI et al (2009) Polychlorinated biphenyls and risk of testicular germ cell tumors. Cancer Res 69:1901–1909

    Article  CAS  PubMed  Google Scholar 

  22. Raaschou-Nielsen O, Pavuk M, Leblanc A et al (2005) Adipose organochlorine concentrations and risk of breast cancer among postmenopausal Danish women. Cancer Epidemiol Biomarkers Prev 14:67–74

    CAS  PubMed  Google Scholar 

  23. Demers A, Ayotte P, Brisson J et al (2002) Plasma concentrations of polychlorinated biphenyls and the risk of breast cancer: a congener-specific analysis. Am J Epidemiol 155:629–635

    Article  PubMed  Google Scholar 

  24. Ward EM, Schulte P, Grajewski B et al (2000) Serum organochlorine levels and breast cancer: a nested case-control study of Norwegian women. Cancer Epidemiol Biomarkers Prev 9:1357–1367

    CAS  PubMed  Google Scholar 

  25. Millikan R, DeVoto E, Duell EJ et al (2000) Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina. Cancer Epidemiol Biomarkers Prev 9:1233–1240

    CAS  PubMed  Google Scholar 

  26. Demers A, Ayotte P, Brisson J et al (2000) Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations. Cancer Epidemiol Biomarkers Prev 9:161–166

    CAS  PubMed  Google Scholar 

  27. Helzlsouer KJ, Alberg AJ, Huang HY et al (1999) Serum concentrations of organochlorine compounds and the subsequent development of breast cancer. Cancer Epidemiol Biomarkers Prev 8:525–532

    CAS  PubMed  Google Scholar 

  28. Li D, Jiao L, Porta M (2005) Epidemiology. In: von Hoff DD, Evans DB, Hruban RH (eds) Pancreatic cancer. Jones & Bartlett, Boston, pp 103–117

    Google Scholar 

  29. Ojajärvi A, Partanen T, Ahlbom A et al (2007) Estimating the relative risk of pancreatic cancer associated with exposure agents in job title data in a hierarchical Bayesian meta-analysis. Scand J Work Environ Health 33:325–335

    PubMed  Google Scholar 

  30. Lo AC, Soliman AS, El-Ghawalby N et al (2007) Lifestyle, occupational, and reproductive factors in relation to pancreatic cancer risk. Pancreas 35:120–129

    Article  PubMed  Google Scholar 

  31. Soliman AS, Lo AC, Banerjee M et al (2007) Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution. Carcinogenesis 28:1794–1799

    Article  CAS  PubMed  Google Scholar 

  32. Soler M, Malats N, Porta M et al (1999) Medical conditions in patients with pancreatic and biliary diseases: validity and agreement between data from questionnaires and medical records. Dig Dis Sci 44:2469–2477

    Article  CAS  PubMed  Google Scholar 

  33. Porta M, Costafreda S, Malats N et al (2000) Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. Eur J Epidemiol 16:533–541

    Article  CAS  PubMed  Google Scholar 

  34. Porta M, Zumeta E, Ruiz L et al (2002) The influence of age and gender on serum concentrations of p,p′-DDT, p,p′-DDE and the DDT/DDE ratio in subjects with exocrine pancreatic cancer. Organohalogen Compd 59:351–354

    CAS  Google Scholar 

  35. Porta M, Grimalt JO, Jariod M et al (2007) Influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with exocrine pancreatic cancer. Environ Int 33:946–954

    Article  CAS  PubMed  Google Scholar 

  36. Porta M, Pumarega J, Ferrer-Armengou O et al (2007) Timing of blood extraction in epidemiologic and proteomic studies: results and proposals from the PANKRAS II Study. Eur J Epidemiol 22:577–588

    Article  PubMed  Google Scholar 

  37. Porta M, Bosch de Basea M, Benavides FG et al (2008) Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer. Environ Res 108:370–379

    Article  CAS  PubMed  Google Scholar 

  38. Porta M, Ferrer-Armengou O, Pumarega J et al (2008) Exocrine pancreatic cancer clinical factors were related to timing of blood extraction and influenced serum concentrations of lipids. J Clin Epidemiol 61:695–704

    Article  PubMed  Google Scholar 

  39. Porta M, Jariod M, López T, Pumarega J, Puigdomènech E, Marco E, Malats N, Grimalt JO, Real FX (2009) Correcting serum concentrations of organochlorine compounds by lipids: alternatives to the organochlorine/total lipids ratio. Environ Int 35 (in press)

  40. Crous-Bou M (2009) Clinical and environmental influences on the prevalence of mutations in the K-ras oncogene in patients with pancreatic ductal adenocarcinoma [Doctoral dissertation; Dir.: Porta M]. Universitat Autònoma de Barcelona, Barcelona. In Catalan & English. Available from http://www.imim.es/programesrecerca/epidemiologia/en_documentsgrecm.html. Accessed 18 June 2009

  41. Porta M, Malats N, Belloc J et al (1996) Do we believe what patients say about their neoplastic symptoms? An analysis of factors that influence the interviewer’s judgement. Eur J Epidemiol 12:553–562

    Article  CAS  PubMed  Google Scholar 

  42. Phillips DL, Pirkle JL, Burse VW et al (1989) Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding. Arch Environ Contam Toxicol 18:495–500

    Article  CAS  PubMed  Google Scholar 

  43. Bernert JT, Turner WE, Patterson DG Jr, Needham LL (2007) Calculation of serum “total lipid” concentrations for the adjustment of persistent organohalogen toxicant measurements in human samples. Chemosphere 68:824–831

    Article  CAS  PubMed  Google Scholar 

  44. Armitage P, Berry G, Matthews JNS (2002) Statistical methods in medical research, 4th edn. Blackwell, Oxford

    Google Scholar 

  45. Kleinbaum DG, Kupper LL, Muller KE et al (1998) Applied regression analysis and other multivariable methods, 3rd edn. Duxbury, Pacific Grove

    Google Scholar 

  46. Cocco P, Brennan P, Ibba A et al (2008) Plasma polychlorobiphenyl and organochlorine pesticide level and risk of major lymphoma subtypes. Occup Environ Med 65:132–140

    Article  CAS  PubMed  Google Scholar 

  47. Stolzenberg-Solomon RZ, Vieth R, Azad A et al (2006) A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res 66:10213–10219

    Article  CAS  PubMed  Google Scholar 

  48. Rusiecki JA, Matthews A, Sturgeon S et al (2005) A correlation study of organochlorine levels in serum, breast adipose tissue, and gluteal adipose tissue among breast cancer cases in India. Cancer Epidemiol Biomarkers Prev 14:1113–1124

    Article  CAS  PubMed  Google Scholar 

  49. Petreas M, Smith D, Hurley S et al (2004) Distribution of persistent, lipid-soluble chemicals in breast and abdominal adipose tissues: lessons learned from a breast cancer study. Cancer Epidemiol Biomarkers Prev 13:416–424

    CAS  PubMed  Google Scholar 

  50. Quintana PJ, Delfino RJ, Korrick S et al (2004) Adipose tissue levels of organochlorine pesticides and polychlorinated biphenyls and risk of non-Hodgkin’s lymphoma. Environ Health Perspect 112:854–861

    Article  CAS  PubMed  Google Scholar 

  51. Muscat JE, Britton JA, Djordjevic MV et al (2003) Adipose concentrations of organochlorine compounds and breast cancer recurrence in Long Island, New York. Cancer Epidemiol Biomarkers Prev 12:1474–1478

    CAS  PubMed  Google Scholar 

  52. Woolcott CG, Aronson KJ, Hanna WM et al (2001) Organochlorines and breast cancer risk by receptor status, tumor size, and grade (Canada). Cancer Causes Control 12:395–404

    Article  CAS  PubMed  Google Scholar 

  53. Stellman SD, Djordjevic MV, Britton JA et al (2000) Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York. Cancer Epidemiol Biomarkers Prev 9:1241–1249

    CAS  PubMed  Google Scholar 

  54. Aronson KJ, Miller AB, Woolcott CG et al (2000) Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev 9:55–63

    CAS  PubMed  Google Scholar 

  55. Schildkraut JM, Demark-Wahnefried W, DeVoto E et al (1999) Environmental contaminants and body fat distribution. Cancer Epidemiol Biomarkers Prev 8:179–183

    CAS  PubMed  Google Scholar 

  56. Longnecker MP, Klebanoff MA, Gladen BC et al (1999) Serial levels of serum organochlorines during pregnancy and postpartum. Arch Environ Health 54:110–114

    CAS  PubMed  Google Scholar 

  57. López-Carrillo L, Torres-Sánchez L, López-Cervantes M et al (1999) The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: some methodological considerations. Environ Res 81:142–145

    Article  PubMed  Google Scholar 

  58. Moysich KB, Ambrosone CB, Vena JE et al (1998) Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 7:181–188

    CAS  PubMed  Google Scholar 

  59. Stellman SD, Djordjevic MV, Muscat JE et al (1998) Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York. Cancer Epidemiol Biomarkers Prev 7:489–496

    CAS  PubMed  Google Scholar 

  60. Høyer AP, Grandjean P, Jørgensen T et al (1998) Organochlorine exposure and risk of breast cancer. Lancet 352:1816–1820

    Article  PubMed  Google Scholar 

  61. Gammon MD, Wolff MS, Neugut AI et al (1996) Treatment for breast cancer and blood levels of chlorinated hydrocarbons. Cancer Epidemiol Biomarkers Prev 5:467–471

    CAS  PubMed  Google Scholar 

  62. Krieger N, Wolff MS, Hiatt RA et al (1994) Breast cancer and serum organochlorines: a prospective study among White, Black, and Asian women. J Natl Cancer Inst 86:589–599

    Article  CAS  PubMed  Google Scholar 

  63. Howsam M, Grimalt JO, Guinó E et al (2004) Organochlorine exposure and colorectal cancer risk. Environ Health Perspect 112:1460–1466

    CAS  PubMed  Google Scholar 

  64. Vineis P, Porta M (1996) Causal thinking, biomarkers, and mechanisms of carcinogenesis. J Clin Epidemiol 49:951–956

    Article  CAS  PubMed  Google Scholar 

  65. Porta M (2006) Persistent organic pollutants and the burden of diabetes. Lancet 368:558–559

    Article  PubMed  Google Scholar 

  66. Porta M, Lee DH, Puigdomènech E (2009) Transgenerational inheritance of environmental obesogens. Occup Environ Med 66:141–142

    Article  PubMed  Google Scholar 

  67. Lee DH, Jacobs DR Jr, Porta M (2009) Hypothesis: a unifying mechanism for nutrition and chemicals as lifelong modulators of global DNA hypomethylation. Environ Health Perspect 117 (in press)

  68. Bloom MS, Buck-Louis GM, Schisterman EF, Kostyniak PJ, Vena JE (2009) Changes in maternal serum chlorinated pesticide concentrations across critical windows of human reproduction and development. Environ Res 109:93–100

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by research grants from Generalitat de Catalunya (CIRIT SGR 0241, SGR 0078); ‘Red temática de investigación cooperativa de centros en Cáncer’ (C03/10), ‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’ (C03/09), and CIBER de Epidemiología, Instituto de Salud Carlos III. The authors gratefully acknowledge scientific and technical assistance provided by Paco Real, Núria Malats, Montserrat Fitó, María-Isabel Covas, Elisa Puigdomènech, Magda Gasull, Marta Crous, Magda Bosch de Basea, Silvia Geeraerd, and Yolanda Rovira.

Disclosure of potential conflicts of interest

The authors declare they have no competing financial interests. The study sponsors had no role and no involvement in the study design, nor in the collection, analysis, and interpretation of data; they also had no role and no involvement in the writing of the report, nor in the decision to submit the article for publication.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Miquel Porta.

Additional information

PANKRAS II Study: Multicenter Prospective Study on the Role of K-ras and other Genetic Alterations in the Diagnosis, Prognosis, and Etiology of Pancreatic and Biliary Diseases.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Porta, M., Pumarega, J., López, T. et al. Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer. Cancer Causes Control 20, 1893–1906 (2009). https://doi.org/10.1007/s10552-009-9383-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-009-9383-2

Keywords

Navigation