Cancer incidence of 2,4-D production workers

Our plain-English summary of Cancer incidence of 2,4-D production workers, by C. Burns, K. Bodner, G. Swaen, et al (International Journal of Environmental Research and Public Health, 2011).

The study

• Authors: C. Burns, K. Bodner, G. Swaen, J. Collins, K. Beard, M. Lee
• Journal: International Journal of Environmental Research and Public Health
• Published: 2011;8(9):3579-90
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Despite showing no evidence of carcinogenicity in laboratory animals, the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been associated with non-Hodgkin lymphoma (NHL) in some human epidemiology studies, albeit inconsistently. We matched an existing cohort of 2,4-D manufacturing employees with cancer registries in three US states resulting in 244 cancers compared to 276 expected cases. The Standardized Incidence Ratio (SIR) for the 14 NHL cases was 1.36 (95% Confidence Interval (CI) 0.74-2.29). Risk estimates were higher in the upper cumulative exposure and duration subgroups, yet not statistically significant. There were no clear patterns of NHL risk with period of hire and histology subtypes. Statistically significant results were observed for prostate cancer (SIR = 0.74, 95% CI 0.57-0.94), and "other respiratory" cancers (SIR = 3.79, 95% CI 1.22-8.84; 4 of 5 cases were mesotheliomas). Overall, we observed fewer cancer cases than expected, and a non statistically significant increase in the number of NHL cases.

In plain English

This study counted cancers among men who had worked in operations making, formulating or packaging the herbicide 2,4-D at a Dow Chemical Company site in Midland, Michigan. The authors linked 1316 men who worked there between 1945 and 1994 to the Michigan cancer registry for 1985 to 2007. They compared the men's cancer counts with the number expected from Michigan rates for white men. In the main group of 1256 men, there were 244 cancers against 276.08 expected. Non-Hodgkin lymphoma occurred in 14 men against 10.27 expected (SIR 1.36, 95% CI 0.74 to 2.29), which was not statistically significant. Prostate cancer was lower than expected (62 cases, SIR 0.74, 95% CI 0.57 to 0.94), a statistically significant reduction. "Other respiratory" cancers were higher than expected: 5 cases against 1.32 expected (SIR 3.79, 95% CI 1.22 to 8.84), and four of the five were mesotheliomas. The study did not assess asbestos. The authors suggested these four men may have been exposed to asbestos in other jobs or settings, but confidentiality rules prevented them from checking job histories. The authors concluded there was no excess of overall cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study of cancer incidence, linking a worker cohort to state cancer registries and computing standardized incidence ratios (SIRs, the observed number of cancers divided by the number expected)
• Who was studied: 1316 men who worked in 2,4-D operations at The Dow Chemical Company in Midland, Michigan, at any time between 1945 and 1994 and were alive on 1 January 1985. They were followed to 31 December 2007. The main analysis (Cohort 2) included 1256 men and 23,354 person-years. Women were excluded because there were only 50.
• Exposure: The herbicide 2,4-D. Each job was given a relative exposure index (0.005, 0.05, 0.5 or 5 units) based on industrial hygiene monitoring and workplace practices, and this was summed over time as unit-years. Asbestos exposure was not assessed.
• Main results:
  • All cancers, Cohort 2: 244 cancers among 1256 men, against 276.08 expected (SIR 0.88, 95% CI 0.78 to 1.00).
  • Non-Hodgkin lymphoma, Cohort 2: 14 cases against 10.27 expected (SIR 1.36, 95% CI 0.74 to 2.29).
  • Non-Hodgkin lymphoma by length of work: the highest SIR was in men with 5 or more years in 2,4-D work (4 cases against 1.30 expected, SIR 3.08, 95% CI 0.84 to 7.88). None of the exposure or duration subgroup results was statistically significant (test for trend by duration, p = 0.12).
  • Prostate cancer, Cohort 2: 62 cases, statistically significantly lower than expected (SIR 0.74, 95% CI 0.57 to 0.94).
  • "Other respiratory" cancers, Cohort 2: 5 cases against 1.32 expected (SIR 3.79, 95% CI 1.22 to 8.84). This category excludes larynx, bronchus, trachea and lung, and includes the nasal cavity, accessory sinuses, pleura and other sites.
  • Of the 5 "other respiratory" cancers, 4 were mesotheliomas and 1 was a carcinoma of the sinuses.
  • The authors suggested the four men with mesothelioma may have been exposed to asbestos long ago in other departments at the site, in jobs elsewhere, or outside work.
• The authors' conclusion: The authors concluded that there was no excess of overall cancer in this cohort of 2,4-D manufacturing and formulation workers, that prostate cancer was significantly reduced, and that they found no statistically significant risk of non-Hodgkin lymphoma.
• Limitations the authors state:
  • Because of a confidentiality agreement with the state health department, the authors could not identify the cancer cases or review the job histories of the men with mesothelioma.
  • Workers may also have been exposed to other pesticides and industrial chemicals.
  • The non-Hodgkin lymphoma subgroup findings rested on small numbers of cases, and none was statistically significant.
  • There was no information on cancer risk factors other than age and race.
  • The main uncertainty was how many person-years each man was at risk while living in Michigan. The authors addressed this with three alternative follow-up definitions (Cohorts 1 to 3).
  • The relative exposure measures may not be optimal.
  • Women were too few (50) to give meaningful risk estimates.

Topics

Medical terms in this study, explained in our Lexicon: Epidemiology, Standardized Incidence Ratio (SIR), confidence interval, Cumulative Exposure, Histology, Mesothelioma.

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• Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma — E.T. Chang, E.C. Lau, et al. (2017)
• Cancer mortality among man-made vitreous fiber production workers — C.E. Rossiter, H.G. Grimm (1998)
• Asbestos exposure, smoking habits, and cancer incidence among production and maintenance workers in an electrochemical plant — B. Hilt, S. Langård, et al. (1985)
• A cancer incidence and mortality study of Dow Chemical Canada Inc. manufacturing sites — C. Burns, K. Harrison, et al. (2005)

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