Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Exposure to organochlorine pesticides is independent risk factor of hepatocellular carcinoma: A case–control study

Journal of Exposure Science & Environmental Epidemiology volume 21, pages 601–608 (2011)Cite this article

Subjects

A Retraction to this article was published on 22 August 2012

Abstract

Primary hepatocellular carcinoma (HCC) is highly prevalent in China. Although hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are considered the major risk factors, among the high-risk cohorts only a small fraction develops liver cancer. Therefore, we investigated if organochlorine pesticides (OCPs) exposure contributed to HCC risk in the Xiamen population. The questionnaire database was built from 346 HCC cases and 961 healthy controls during 2007–2009. The serum levels of α-, β-, γ-, δ-HCH, p, p′-DDT, p, p′-DDE, o, p′-DDT and p, p′-DDD were measured by gas chromatography-tandem mass spectrometer and statistical analysis was done using SPSS16. Significantly, we observed p, p′-DDT, p, p′-DDE, and at first time β-HCH displayed quartile dose-dependent HCC risk trends; p, p′-DDT showed positive (i.e., synergistic) interactions with HBV, diabetes mellitus, AFB1 and polycyclic aromatic hydrocarbon (PAH) exposure, but negative (i.e., antagonistic) interaction with heavy drinking; p, p′-DDE had positive interaction with PAH but negative interaction with HBV and p, p′-DDT; and β-HCH was positively interacted with p, p′-DDT but negatively interacted with heavy drinking and diabetes. p, p′-DDT, p, p′-DDE and β-HCH were independent HCC risk factors. Because of their synergistic interactions with other factors, the high level exposure combined with common AFB1 and HBV exposure in the investigated area may greatly enhance the risk of HCC.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Altekruse S.F., McGlynn K.A., and Reichman M.E. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009: 27: 1485–1491.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chu F.S., and Li G.Y. Simultaneous occurrence of fumonisin B-1 and other mycotoxins in moldy corn collected from the Peoples-Republic-of-China in regions with high incidences of esophageal cancer. Appl Environ Microbiol 1994: 60: 847–852.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cocco P., Blair A., Congia P., Saba G., Flore C., and Ecca M.R., et al. Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: a preliminary report. Arch Environ Health 1997: 52: 299–303.

    Article  CAS  PubMed  Google Scholar 

  • Cocco P., Fadda D., Billai B., D’Atri M., Melis M., and Blair A. Cancer mortality among men occupationally exposed to dichlorodiphenyltrichloroethane. Cancer Res 2005: 65: 9588–9594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cocco P., Kazerouni N., and Zahm S.H. Cancer mortality and environmental exposure to DDE in the United States. Environ Health Perspect 2000: 108: 1–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Codru N., Schymura M.J., Negoita S., Rej R., Carpenter D.O., and Env A.T.F. Diabetes an relation to serum levels of polychlorinated biphenyls and chlorinated pesticides an adult native Americans. Environ Health Perspect 2007: 115: 1442–1447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dekoning E.P., and Karmaus W. PCB exposure in utero and via breast milk. A review. J Expo Anal Environ Epidemiol 2000: 10: 285–293.

    Article  CAS  PubMed  Google Scholar 

  • Deng Z.L., Ma Y., Pan L.X., and Peng H.Z. A molecular epidemiologic marker of hepatocellular carcinoma from aflatoxin B1 contaminated area in the Southwest of Guangxi, China. J Cancer Res 1997: 9: 167–169.

    CAS  Google Scholar 

  • Donato F., Tagger A., Gelatti U., Parrinello G., Boffetta P., and Albertini A., et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Amer J Epidemiol 2002: 155: 323–331.

    Article  CAS  Google Scholar 

  • El-Serag H.B., and Rudolph L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007: 132: 2557–2576.

    Article  CAS  PubMed  Google Scholar 

  • El-Shahawi M.S., Hamza A., Bashammakh A.S., and Al-Saggaf W.T. An overview on the accumulation, distribution, transformations, toxicity and analytical methods for the monitoring of persistent organic pollutants. Talanta 2010: 80: 1587–1597.

    Article  CAS  PubMed  Google Scholar 

  • Eskenazi B., Chevrier J., Rosas L.G., Anderson H.A., Bornman M.S., and Bouwman H., et al. The pine river statement: human health consequences of DDT use. Environ Health Perspect 2009: 117: 1359–1367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Figatalamanca I., Mearelli I., and Valente P. Mortality in a cohort of pesticide applicators in an urban setting. Int J Epidemiol 1993: 22: 674–676.

    Article  CAS  Google Scholar 

  • Garcia M., Jemal A., Ward E.M., Center M.M., Hao Y., and Siegel R.L., et al. Global Cancer Facts & Figures 2007. American Cancer Society, Atlanta, GA, 2007.

    Google Scholar 

  • Hassan M.M., Spitz M.R., Thomas M.B., El-Deeb A.S., Glover K.Y., and Nguyen N.T., et al. Effect of different types of smoking and synergism with Hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study. Int J Cancer 2008: 123: 1883–1891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imai Y., Tamura S., Tanaka H., Hiramatsu N., Kiso S., and Doi Y., et al. Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained virological responders. J Viral Hepatitis 2010: 17: 185–191.

    Article  CAS  Google Scholar 

  • Jaga K., and Dharmani C. Global surveillance of DDT and DDE levels in human tissues. Int J Occup Med Environ Health 2003: 16: 7–20.

    PubMed  Google Scholar 

  • Jemal A., Siegel R., Ward E., Hao Y., Xu J., and Thun M.J. Cancer statistics, 2009. CA Cancer J Clin 2009: 59: 225–249.

    Article  PubMed  Google Scholar 

  • Källberg H., Ahlbom A., and Alfredsson L. Calculating measures of biological interaction using R. Eur J Epidemiol 2006: 21: 571–573.

    Article  PubMed  Google Scholar 

  • Kirk G.D., Camus-Randon A.M., Mendy M., Goedert J.J., Merle P., and Trepo C., et al. Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia. J Natl Cancer Inst 2000: 92: 148–153.

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa T., Hino O., Nomura K., and Sugano H. Dose-response studies on promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis. Carcinogenesis 1984: 5: 1653–1656.

    Article  CAS  PubMed  Google Scholar 

  • Li F.Q., Yoshizawa T., Kawamura O., Luo X.Y., and Li Y.W. Aflatoxins and fumonisins in corn from the high-incidence area for human hepatocellular carcinoma in Guangxi, China. J Agric Food Chem 2001: 49: 4122–4126.

    Article  CAS  PubMed  Google Scholar 

  • Liu L.F., Zhang J.L., Chen Q., Chang Y., and Lin J.S. Cyclooxygenase-2 gene -1195G/A genotype is associated with the risk of HBV-induced HCC: a case-control study in Han Chinese people. Front Med China 2010: 4: 6.

    Google Scholar 

  • Liu Y., and Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect 2010: 118: 818–824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGlynn K.A., Abnet C.C., Zhang M., Sun X.D., Fan J.H., and O’Brien T.R., et al. 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 2006: 98: 1005–1010.

    Article  CAS  PubMed  Google Scholar 

  • McGlynn K.A., and London W.T. Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005: 19: 3–23.

    Article  PubMed  Google Scholar 

  • Morgan D.P., and Roan C.C. Absorption, storage, and metabolic conversion of ingested DDT and DDT metabolites in man. Arch Environ Health 1971: 22: 301–308.

    Article  CAS  PubMed  Google Scholar 

  • Niu J.J., Su Y.H., Han Y.F., Zhao R., Sun X.L., and Guo F., et al. Synergistic effects of different types of smoking and other risk factors on risk of hepatocellular carcinoma in Xiamen, China. Chin J Epidemiol 2010: 31: 6.

    CAS  Google Scholar 

  • Onishchenko N., Karpova N., Sabri F., Castren E., and Ceccatelli S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J Neurochem 2008: 106: 1378–1387.

    Article  CAS  PubMed  Google Scholar 

  • Parkin D.M., Bray F., Ferlay J., and Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001: 94: 153–156.

    Article  CAS  PubMed  Google Scholar 

  • Parkin D.M., Bray F., Ferlay J., and Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005: 55: 74–108.

    Article  PubMed  Google Scholar 

  • POPRC. Risk profile on beta hexachlorocyclohexane, Addendum of the Report of the Persistent Organic Pollutants Review Committee (POPRC) on the work of its third meeting, Geneva, Switzerland, 2007.

  • Qian G.S., Ross R.K., Yu M.C., Yuan J.M., Gao Y.T., and Henderson B.E., et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China. Cancer Epidemiol Biomarkers Prev 1994: 3: 3–10.

    CAS  PubMed  Google Scholar 

  • Qiu X., Zhu T., Yao B., Hu J., and Hu S. Contribution of dicofol to the current DDT pollution in China. Environ Sci Technol 2005: 39: 4385–4390.

    Article  CAS  PubMed  Google Scholar 

  • Qu C.X., Kamangar F., Fan J.H., Yu B., Sun X.D., and Taylor P.R., et al. Chemoprevention of primary liver cancer: a randomized, double-blind trial in Linxian, China. J Natl Cancer Inst 2007: 99: 1240–1247.

    Article  PubMed  Google Scholar 

  • Ruzzin J., Petersen R., Meugnier E., Madsen L., Lock E.J., and Lillefosse H., et al. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environ Health Perspect 2010: 118: 465–471.

    Article  CAS  PubMed  Google Scholar 

  • Shen F.M., Lee M.K., Gong H.M., Cai X.Q., and King M.C. Complex segregation analysis of primary hepatocellular carcinoma in Chinese families: interaction of inherited susceptibility and hepatitis B viral infection. Am J Hum Genet 1991: 49: 88–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shen H., Main K.M., Virtanen H.E., Damggard I.N., Haavisto A.M., and Kaleva M., et al. From mother to child: investigation of prenatal and postnatal exposure to persistent bioaccumulating toxicants using breast milk and placenta biomonitoring. Chemosphere 2007: 67: S256–S262.

    Article  CAS  PubMed  Google Scholar 

  • Shen H., Maine K.M., Andersson A.M., Damgaard I.N., Virtanen H.E., and Skakkebaek N.E., et al. Concentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland. Hum Reprod 2008: 23: 201–210.

    Article  CAS  PubMed  Google Scholar 

  • Sundberg S.E., Ellington J.J., and Evans J.J. A simple and fast extraction method for organochlorine pesticides and polychlorinated biphenyls in small volumes of avian serum. J Chromatogr B 2006: 831: 99–104.

    Article  CAS  Google Scholar 

  • Szymanska K., Chen J.G., Cui Y., Gong Y.Y., Turner P.C., and Villar S., et al. TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China. Cancer Epidemiol Biomarkers Prev 2009: 18: 1638–1643.

    Article  CAS  PubMed  Google Scholar 

  • Vetter W., and Schurig V. Enantioselective determination of chiral organochlorine compounds in biota by gas chromatography on modified cyclodextrins. J Chromatogr A 1997: 774: 143–175.

    Article  CAS  PubMed  Google Scholar 

  • Wang J., and Liu X.M. Contamination of aflatoxins in different kinds of foods in China. Biomed Environ Sci 2007: 20: 483–487.

    CAS  PubMed  Google Scholar 

  • Wang J.S., Huang T., Su J.J., Liang F., Wei Z.L., and Liang Y.Q., et al. Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People's Republic of China. Cancer Epidemiol Biomarker Prev 2001: 10: 143–146.

    CAS  Google Scholar 

  • Wang X.Q., Gao P.Y., Lin Y.Z., and Chen C.M. Studies on hexachlorocyclohexane and DDT contents in human cerumen and their relationships to cancer mortality. Biomed Environ Sci 1988: 1: 138–151.

    CAS  PubMed  Google Scholar 

  • Welzel T.M., Katki H.A., Sakoda L.C., Evans A.A., London W.T., and Chen G., et al. Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort. Cancer Epidemiol Biomarkers Prev 2007: 16: 1279–1282.

    Article  CAS  PubMed  Google Scholar 

  • WHO. Environmental Health Criteria 123, Alpha- and beta-Hexachlorocyclohexanes, Geneva, Switzerland, 1992: http://www.inchem.org/documents/ehc/ehc/ehc123.htm(Accessed November 2, 2010).

  • WHO/IDF. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: a report of WHO/IDF consultation, Geneva, Switzerland, 2006.

  • Willett K.L., Ulrich E.M., and Hites R.A. Differential toxicity and environmental fates of hexachlorocyclohexane isomers. Environ Sci Technol 1998: 32: 2197–2207.

    Article  CAS  Google Scholar 

  • Williams G.M., and Numoto S. Promotion of mouse liver neoplasms by the organochlorine pesticides chlordane and heptachlor in comparison to dichlorodiphenyltrichloroethane. Carcinogenesis 1984: 5: 1689–1696.

    Article  CAS  PubMed  Google Scholar 

  • Wu H.C., Wang Q., Wang L.W., Yang H.I., Ahsan H., and Tsai W.Y., et al. Polycyclic aromatic hydrocarbon- and aflatoxin-albumin adducts, hepatitis B virus infection and hepatocellular carcinoma in Taiwan. Cancer Lett 2007: 252: 104–114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H.C., Wang Q., Yang H.I., Ahsan H., Tsai W.Y., and Wang L.Y., et al. Urinary 15-F-2t-isoprostane, aflatoxin B-1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan. Carcinogenesis 2008: 29: 971–976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L., Parkin D.M., Whelan S., Zhang S., Chen Y., and Lu F., et al. Statistics on cancer in China: cancer registration in 2002. Eur J Cancer Prev 2005: 14: 329–335.

    Article  CAS  PubMed  Google Scholar 

  • Yeh F.S., Yu M.C., Mo C.C., Luo S., Tong M.J., and Henderson B.E. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res 1989: 49: 2506–2509.

    CAS  PubMed  Google Scholar 

  • Zhao B.H., Guo F., Liu S., and Pan L.L. The study on the interactions between polycyclic aromatic hydrocarbon-albumin adducts and various risk factors to primary hepatocellular carcinoma. Chin J Prev Med 2010: 44: 427–432.

    CAS  Google Scholar 

Download references

Acknowledgements

The work was supported by Chinese Academy of Sciences (CAS) 100 Talents Program for Human Exposure to Environmental Pollutant and Health Effect, Xiamen Municipal Science and Technology Program (3502Z20073015), CAS/SAFEA International Partnership Program for Creative Research Teams (KZCX2-YW-T08) and Ministry of Science and Technology of the People's Republic of China for Combined Pollution and Ecosystem Health in Urban Agglomeration (2009DFB90120). We thank all the persons who contributed their samples and work in this study. We also thank Prof. Jay Gan (Department of Environmental Sciences, University of California, Riverside, USA) for his help in improving the English and his nice comments on the report.

Author information

Authors and Affiliations

  1. Medical College of Xiamen University, Xiamen, 361005, PR China

    Benhua Zhao, Sheng Liu & Fei Guo

  2. Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, PR China

    Heqing Shen & Feng Liu

  3. Xiamen Center for Disease Control and Prevention, Xiamen, 361021, PR China

    Jianjun Niu

  4. Zhangzhou Center for Disease Control and Prevention, Xiamen, 363000, PR China

    Xueli Sun

Authors
  1. Benhua Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heqing Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianjun Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xueli Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heqing Shen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, B., Shen, H., Liu, F. et al. Exposure to organochlorine pesticides is independent risk factor of hepatocellular carcinoma: A case–control study. J Expo Sci Environ Epidemiol 21, 601–608 (2011). https://doi.org/10.1038/jes.2011.24

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jes.2011.24

Keywords

Search

Advanced search

Quick links