Environment and Breast Cancer: Science Review

Evidence From Humans
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Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study
Kogevinas, M., Becher, H., Benn, T., Bertazzi, P. A., Boffetta, P., Bueno-de-Mesquita, H. B., Coggon, D., Colin, D., Flesch-Janys, D., Fingerhut, M., Green, L., Kauppinen, T., Littorin, M., Lynge, E., Mathews, J. D., Neuberger, M., Pearce, N., Saracci, R. American Journal of Epidemiology. 1997. 145:12, 1061-75.
Topic area
Environmental pollutant - Dioxins, TCDD, pesticide, chlorophenoxy herbicide,
Study design
Other: Cohort mortality follow up
Funding agency
NIEHS Other: European Commission, Government of Ca
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number in Cohort
Cohort: 20,851 exposed male and female workers (1,012 females)
Country where study was conducted
International: 12 countries
Cohort participation rate
Small loss to follow-up
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Male and female workers in 36 cohorts exposed to phenoxy herbicides, chlorophenols, and dioxins in 12 countries followed 1939-1992. Compared with World Health Organization mortality data by country.
Comment about participation selection
Most comprehensive inclusion of exposed workers to date.
Exposure Investigated
Exposures investigated
Worked with chlorophenoxy herbicides, chlorophenols, likely contaminated by dioxins, TCDD. Classification from individual job records, questionnaires, and measurements of TCDD in serum and adipose tissue and the workplace for some workers. Classificatio
Exposure assessment comment
In some cohorts serum, adipose, and workplace samples were available to assess concordance with exposure assessment by job history. Samples show that exposed workers have higher serum TCDD levels than the general population, but many workers classified as exposed have levels similar to the comparison population. Serum and adipose levels were available for males only. Categories are broad, resulting in misclassification. Exposure involves multiple chemicals that cannot be separated. Authors state that the different mix of chemicals produced in the manufacturing centers weighs against confounding by another unidentified chemical exposure.
Statistical Analysis
Breast cancer outcome investigated
Mortality from breast cancer from 1939-1992
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Not adequately controlled. Sex, age in 5-year groups, calendar periods in 5-year intervals, country.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Standardized mortality ratio based on Poisson distribution.
Strength of associations reported
exposed to TCDD or higher chlorinated dioxins (9 deaths) SMR 2.16 (0.99-4.10)
not exposed to TCDD or higher chlorinated dioxins (3 deaths) SMR 0.53 (0.11-1.56)
all workers exposed to any phenoxy herbicide or chlorophenols (12 deaths) SMR (1.23 (0.63 - 2.14)
exposed to TCDD or higher chlorinated dioxins (2 deaths) SMR 2.56 (0.31-9.26)
not exposed to TCDD or higher chlorinated dioxins (0 deaths)
all workers exposed to any phenoxy herbicide or chlorophenols (2 deaths) SMR 1.55 (0.19-5.60)
Results Comments
Possible healthy worker effects or effects of other differences between employed and not employed women. Authors state the comparison within the cohort of effects for those who were/were not exposed to TCDD provides some reassurance that confounding by lifestyle factors is not the explanation for TCDD results. Authors state that the excess in female breast cancer mortality occurred within the German cohort, which included most of the TCDD-exposed female production workers; and this group was not included in the previous follow-up reported by Saracci et al. (1991).
Author address
Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, Lyon, France.
Reviewers Comments
TCDD is demonstrated to cause cancer at multiple sites in animals.