You are here

  • Home
  • Archive
  • Volume 70, Issue 12
  • Cholangiocarcinoma among workers in the printing industry: using the NOCCA database to elucidate the generalisability of a cluster report from Japan

Article Text

Article menu
Short report
Workplace
Cholangiocarcinoma among workers in the printing industry: using the NOCCA database to elucidate the generalisability of a cluster report from Japan
  1. Jelle Vlaanderen1,
  2. Kurt Straif2,
  3. Jan Ivar Martinsen3,
  4. Timo Kauppinen4,
  5. Eero Pukkala5,6,
  6. Pär Sparén7,
  7. Laufey Tryggvadottir8,9,
  8. Elisabete Weiderpass3,7,10,11,
  9. Kristina Kjaerheim3
  1. 1Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
  2. 2Section of IARC Monographs, International Agency for Research on Cancer, Lyon, France
  3. 3Cancer Registry of Norway, Oslo, Norway
  4. 4Department of Occupational Health, Finnish Institute of Occupational Health, Helsinki, Finland
  5. 5School of Health Sciences, University of Tampere, Tampere, Finland
  6. 6Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
  7. 7Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  8. 8Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  9. 9Icelandic Cancer Registry, Reykjavik, Iceland
  10. 10Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
  11. 11Folkhälsan Research Centre, Samfundet Folkhälsan, Helsinki, Finland
  1. Correspondence to Dr K Straif, International Agency for Research on Cancer, Section of IARC, Monographs, 150 Cours Albert Thomas, 69372 Lyon, Cedex 08, France; straifk{at}iarc.fr

Abstract

Objectives A cluster of 11 cases of cholangiocarcinoma (CC) was observed in a small Japanese printing firm. To elucidate whether the identified cluster is indicative of an elevated risk of CC among workers in the printing industry at large, we explored the risk of cancer of the liver and CC among individuals employed in the printing industry in a large cohort set-up in four Nordic countries (Finland, Iceland, Norway and Sweden) over a period of 45 years.

Methods The cohort was set-up by linking occupational information from censuses to national cancer registry data utilising personal identity codes in use in all Nordic countries. We calculated standardised incidence ratios (SIRs) for men and women working in the printing industry, and stratified by occupational category (typographers, printers, lithographers, bookbinders).

Results Among men, we observed elevated SIRs for cancer of the liver (1.35, 95% CI 1.14 to 1.60; 142 cases), specifically intrahepatic CC (2.34, 95% CI 1.45 to 3.57; 21 cases). SIRs for liver cancer were especially elevated among printers and lithographers, and SIRs for intrahepatic CC among typographers and printers. SIRs for extrahepatic CC were not elevated. SIRs for women followed a similar pattern but the number of cases was low.

Conclusions Our study supports the notion that the finding of excess CC risk among workers in a small Japanese printing firm possibly extends beyond this specific firm and country. Further studies should focus on the specific exposures that occur in the printing industry.

  • Printers
  • Liver cancer
  • Cholangiocarcinoma

https://doi.org/10.1136/oemed-2013-101500

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    What is already known about this subject

    • Some epidemiological evidence points towards an excess risk of liver cancer among workers in the printing industry.

    • Recently, a cluster of 11 cholangiocarcinoma cases was observed in a small Japanese printing firm.

    What this paper adds

    • The Nordic Occupational Cancer Study (NOCCA) cohort has proven useful for an instant investigation following up a report of a cancer cluster.

    • We provide evidence indicative of an excess risk of liver cancer, specifically intrahepatic cholangiocarcinoma, among workers in the Nordic printing industry.

    Introduction

    In a recent publication, Kumagai et al1 reported on a cluster of 11 current and former employees of a small printing plant in Osaka, Japan, that developed cholangiocarcinoma (CC) (International Classification of Diseases 10th revision (ICD-10) C22.1 and C24.0). To elucidate whether the identified cluster is indicative for an elevated risk of CC among workers in the printing industry at large, we explored the risk of cancer of the liver, specifically CC, among individuals employed in the printing industry in a large cohort set-up in four Nordic countries (Finland, Iceland, Norway and Sweden), part of the Nordic Occupational Cancer Study (NOCCA).2

    The printing industry

    Exposures in the printing industry are mainly related to the use of ink (oil mist containing ink) and cleaning agents (eg, benzene, toluene, chlorinated solvents).3 In the early 20th century, printing workers were also exposed to lead dust and fumes but by the mid-1970s these exposures were gradually phased out due to technical modifications of the printing process.3 Highest exposures related to the use of ink and cleaning agents are likely incurred by printers (including lithographers) that operate and clean the printing presses. Typographers set and arrange printing type by hand and machine, and are conceivably also exposed to ink and cleaning agents to a certain extent. Print finishing and binding workers may have been exposed to solvents through the use of glue and paper dust.4 ,5

    Cholangiocarcinoma

    CC is a tumour arising from the malignant transformation of the epithelial cells lining the biliary tract, accounting for 10–20% of all primary liver cancers.6 CC is further classified as intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC), based on the anatomical location of the tumour. Major risk factors for ICC include liver infestation with flukes and thorium-232 and its decay products.7 ,8 ECC is primarily associated with gallstones (associated with physical inactivity, obesity and oestrogen use) and primary sclerosing cholangitis (an autoimmune disease).9

    In 1996, the International Agency for Research on Cancer (IARC) concluded that there was limited epidemiological evidence for excess cancer risk due to occupational exposure related to printing processes.3 However, that conclusion was primarily based on the evidence of excess risks of lung and bladder cancer.3

    Methods

    Study cohort

    All subjects aged 30–64 years, who participated in the 1960, 1970, 1980/1981 and/or 1990 censuses in Finland, Iceland, Norway and Sweden, and who were still alive and living in the respective countries on 1 January in the year following the census, were included in the study cohort. Data from Denmark were not included as information on occupational subgroups was not available at the time of analysis. Personal identification numbers were used to link the census data of each individual to the national cancer and population registries. The cohort was followed-up for cancer incidence during the period from 1 January of the year after the first available census until emigration, death or 31 December of the following years: in Finland 2005, in Iceland 2004, in Norway 2003 and in Sweden 2005. The seventh revision of the International Classification of Diseases (ICD-7),10 with country specific modifications, served as a common coding system for all countries through the study period, either as the main system or as a system used in parallel with newer codes.11 ,12

    We included the following cancer outcomes in our analysis: liver, ICC and ‘ECC, ampulla of Vater and gall bladder’. Liver cancer was defined as the aggregation of hepatocellular carcinoma and ICC. The online supplementary table S1 provides an overview of the country specific disease classification codes that were included for each outcome. Individuals were assigned to an occupational category based on Nordic adaptations of the International Standard Classification of Occupations (ISCO) from 1958 (NYK).2 All individuals classified as ‘printers and related workers’ were included in the current analysis. Online supplementary table S2 provides an overview of the country specific occupational codes that were included for each occupational category.

    Further details on the cohort have been described in detail previously.2

    Statistical analysis

    We calculated standardised incidence ratios (SIRs) by estimating the expected number of cases using national cancer incidence rates. Observed number of cases and person years were stratified by country, sex, 5 year age and 5 year calendar period categories. SIRs were calculated for the full study population for men and women separately, and further stratified by occupational category (typographers, printers, lithographers, bookbinders, ‘other occupations’), calendar period (1961–1975, 1976–1990, 1991–2005) and attained age (30–49 years, 50–69 years, 70+ years).

    Results

    A total of 74 949 individuals in the NOCCA study (excluding Denmark) were categorised as ‘printers and related workers’; 72% of these were men, contributing 1 373 940 person years. Women contributed 536 126 person years. Most individuals were from Sweden (54%) and Finland (27%), and 18% were from Norway and 1% from Iceland.

    SIRs are reported in table 1. Among men, the SIR for cancer of the liver was 1.35 (95% CI 1.14 to 1.60; 142 cases) and for ICC 2.34 (95% CI 1.45 to 3.57; 21 cases). The SIR for ‘ECC, ampulla of Vater and gall bladder’ was not elevated. Among women, the SIR for liver cancer was 1.35 (95% CI 0.92 to 1.90; 32 cases) and for ICC 1.95 (95% CI 0.84 to 3.85; eight cases). The SIR for cancer of ‘ECC, ampulla of Vater and gall bladder’ was not elevated.

    View this table:
    Table 1

    Observed numbers of liver cancer, intrahepatic cholangiocarcinoma and cancer of ‘extrahepatic cholangiocarcinoma, ampulla of Vater and gall bladder’, and standardised incidence ratios, 1961–2005, in the printing industry of four Nordic countries, stratified by occupation

    In men, SIRs for liver cancer were especially elevated among printers (SIR 2.22; 25 cases) and lithographers (SIR 2.38; eight cases), and SIRs for ICC among typographers (SIR 2.01; 11 cases) and printers (SIR 3.54; six cases). SIRs for cancer of ‘ECC, ampulla of Vater and gall bladder’ were not elevated in any of the occupational categories. Among women, evaluation of SIRs for specific occupational categories was hampered by a limited number of cases. Some evidence for elevated SIRs was observed for liver cancer among lithographers (SIR 5.03; two cases) and for ICC among typographers (SIR 3.14; three cases) and lithographers (SIR 10.34, one case). We did not observe trends in SIRs with either calendar period or age category for cancer of the liver and gall bladder among men or women (results not shown).

    Discussion

    The observation that SIRs for ICC are particularly elevated for printers and lithographers is corroborated by the notion that the highest exposures related to the use of ink and cleaning agents are likely incurred in these occupational categories. Combining the male printers and lithographers into a single job category results in SIRs of 2.26 (95% CI 1.58 to 3.13) for liver cancer and 3.63 (95% CI 1.68 to 6.89) for ICC. Respective SIRs for women were 0.99 for liver cancer (95% CI 0.32 to 2.39) and 2.44 for ICC (95% CI 0.41 to 8.05). The elevated SIR for ICC among typographers is primarily driven by the large number of cases that was observed in Sweden (SIR for Sweden 2.26; eight cases). Interestingly, in Sweden, lithographers were coded as typographer (see online supplementary table S2) and therefore possibly contributed to the excess risk observed for typographers.

    In a study among Danish printing workers, Lynge et al13 observed an SIR of 1.9 (95% CI 1.1 to 3.1; 15 cases) for liver cancer, similar to the SIR for liver cancer that we observed in our study. Lynge et al13 also reported an SIR of 6.7 (95% CI 2.2 to 15.8; five cases) for liver cancer among the subgroup of lithographers. Other studies have reported both elevated and non-elevated risks for liver and biliary tract cancer among printers and in related occupations (for a tabulated overview see online supplementary table S3). No study in the printing industry reported on the risk of CC specifically.

    Exposures in the Nordic printing industry

    The Japanese report suggests that high exposure to specifically dichloromethane and 1,2-propylene dichloride may have caused the increase in CC among the printer workers.1 In the NOCCA Job Exposure Matrix (JEM), in which exposure prevalence and levels were estimated for the Nordic printing industry covering 1945–1994, workers were estimated to be exposed to benzene (before 1964), gasoline (before 1960), dichloromethane, lead (before 1985), 1,1,1-trichloroethane and toluene.14 Exposures estimates were roughly similar across countries. Assessment of exposure to 1,2-dichloropropane is currently not available in the NOCCA-JEM

    In conclusion, we observed an elevated risk of liver cancer, especially ICC, in a cohort of workers in the Nordic printing industry. Our risk estimates were considerably lower than the estimates observed in the recent study of Japanese printing plant workers (SMR=2900, 95% CI 1100 to 6400; five cases of ICC and six cases of ECC), but in the same range as other studies conducted in the printing industry. A possible explanation is the much higher use of cleaning products in the Japanese printing plant in comparison with the average use in the printing industry, although the Japanese risk estimate might also be inflated due to the nature of the cluster analysis design.1 Exposure to chlorinated solvents, including methylene chloride and propylene dichloride, in the printing industry might be related to the observed excess risks, but further studies should include high quality assessment of the exposure that occurs in the printing industry to substantiate this conclusion. Further insight into occupational risk factors for CC might be gained by conducting case control studies of ICC, ECC and hepatocellular carcinoma nested in large cohorts of workers (eg, the NOCCA cohort), including those with a history of working in the printing industry.

    References

    1. ↵
      1. Kumagai S,
      2. Kurumatani N,
      3. Arimoto A,
      4. et al
      . Cholangiocarcinoma among offset color proof-printing workers exposed to 1,2-dichloropropane and/or dichloromethane. Occup Environ Med 2013;70:508–10.
      OpenUrlAbstract/FREE Full Text
    2. ↵
      1. Pukkala E,
      2. Martinsen JI,
      3. Lynge E,
      4. et al
      . Occupation and cancer—follow-up of 15 million people in five Nordic countries. Acta Oncol 2009;48:646–790.
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      IARC. IARC Monograph on the evaluation of carcinogenic risks to humans, volume 65. Printing processes and printing inks, carbon black and some nitro compounds. Lyon, France: IARC, 1996.
    4. ↵
      1. Rafnsson V
      . Incidence of cancer among bookbinders, printers, photoengravers, and typesetters. Occup Environ Med 2001;58:523–7.
      OpenUrlAbstract/FREE Full Text
    5. ↵
      1. Dahlqvist M
      . Lung function and exposure to paper dust in bookbinders: a pilot study. Ups J Med Sci 1992;97:49–54.
      OpenUrlCrossRefPubMed
    6. ↵
      1. Tyson GL,
      2. El-Serag HB
      . Risk factors for cholangiocarcinoma. Hepatology 2011;54:173–84.
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      1. London WT,
      2. McGlynn KA
      . Liver cancer. In: Schottenfeld D, Fraumeni JF, eds. Cancer epidemiology and prevention. New York: Oxford University Press, 2006:763–86.
    8. ↵
      1. Cogliano VJ,
      2. Baan R,
      3. Straif K,
      4. et al
      . Preventable exposures associated with human cancers. J Natl Cancer Inst 2011;103:1827–39.
      OpenUrlAbstract/FREE Full Text
    9. ↵
      1. Hsing AW,
      2. Rashid A,
      3. Devesa SS,
      4. et al
      . Biliary tract cancer. In: Schottenfeld D, Fraumeni JF, eds. Cancer epidemiology and prevention. New York: Oxford University Press, 2006:787–800.
    10. ↵
      World Health Organization (WHO). International classification of diseases. 7th rev. Geneva: WHO, 1957.
    11. ↵
      World Health Organization (WHO). ICD-O: international classification on diseases for oncology: version 1. Geneva: WHO, 1971.
    12. ↵
      World Health Organization (WHO). ICD-O: international classification on diseases for oncology: version 2. Geneva: WHO, 1990.
    13. ↵
      1. Lynge E,
      2. Rix BA,
      3. Villadsen E,
      4. et al
      . Cancer in printing workers in Denmark. Occup Environ Med 1995;52:738–44.
      OpenUrlAbstract/FREE Full Text
    14. ↵
      1. Kauppinen T,
      2. Heikkilä P,
      3. Plato N,
      4. et al
      . Construction of job-exposure matrices for the Nordic Occupational Cancer Study (NOCCA). Acta Oncol 2009;48:791–800.
      OpenUrlCrossRefPubMedWeb of Science

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

      Files in this Data Supplement:

    Footnotes

    • JV and KS contributed equally.

    • Contributors JV, KS, JIM and KK designed and analysed the study, and drafted the paper. TK, EP, PS, LT, and EW participated in the design of the study and in drafting the paper.

    • Funding This work was financially supported by the Nordic Cancer Union. Part of the work reported in this article was undertaken during the tenure of a Postdoctoral Fellowship from the International Agency for Research on Cancer, partially supported by the European commission FP7 Marie Curie Actions-People-Cofunding of regional, national and international programmes (COFUND).

    • Competing interests None.

    • Ethics approval The study was approved by the ethics committees and data inspection boards in each country.

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

    Linked Articles