Evidence From Humans
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Breast cancer risk and drinking water contaminated by wastewater: a case control study
Brody, J. G., Aschengrau, A., McKelvey, W., Swartz, C. H., Kennedy, T., Rudel, R. A. Environ Health. 2006. 5, 28.
Topic area
Environmental pollutant - Drinking water Nitrate
Study design
Population based case-control
Funding agency
Commonwealth of Massachusetts Komen NIEHS EPA NCI
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on menopausal status
Number of Controls
Controls: 745
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Study participants were of the Cape Cod Breast Cancer and Environment Study, who were permanent residents for at least six months on Cape Cod between 1988-1995. Cases were women diagnosed with invasive breast cancer during the study period, whose diagnosis was reported to the Massachusetts Cancer Registry. Frequency-matched controls (by date of birth and vital status) were chosen by random digit dialing (<65 years) or selected from CMS databases (>=65 years). Deceased controls were selected randomly from death certificates, frequency matched by age and year of death. Participants that lived at a residence not served by a public drinking water supply during the 16-year period prior to diagnosis were excluded because routine monitoring of private wells was not available. Public well monitoring was used as a systematic source of exposure data. Interviews were conducted from 1997 to 2000.
Exposure Investigated
Exposures investigated
Annual excess nitrate-N (i.e. amount above maximum level detected in unimpacted wells) in drinking water, a proxy for wastewater contamination, based on records of measurements for wells in 18 public water districts between 1972-1995. Individual self-repo
How exposure was measured
Environmental sample GIS/geographic location
Exposure assessment comment
Nitrate-N, a drinking water quality measure, serves as a proxy for contamination by wastewater. Because wastewater may be a potential source of endocrine disrupting compounds and mammary gland carcinogens, nitrate-N may also be a proxy for these relevant compounds which have not historically been measured in drinking water. Historical measures of nitrate-N at the district level are useful, but may not be an accurate measurement of the water quality experienced at the tap due to a smaller number of measurements per year as well as other differences in exposure experienced by the participant.
Breast cancer outcome investigated
Primary incident breast cancer
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.
Diagnosis/reference year, age at diagnosis/reference year, birth decade, study, vital status, previous breast cancer diagnosis, age at first birth, family history, education.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Strength of associations reported
Average annual excess nitrate-N concentration (mg/L):
≥1.2 vs. 0 to <0.3: aOR 1.0 (95% CI 0.5-1.9)

Sum of annual excess nitrate-N concentration (mg/L):
≥10 vs. 0 to <0.01: aOR 0.9 (95% CI 0.7-1.2)

Number of years exposed to excess nitrate-N > 1mg/L:
≥8 vs. 0: aOR 0.9 (95% CI 0.5-1.5)

Additional analyses evaluating the impact of homogenous supplies of public drinking water resulted in non-significant estimates. In order to account for differences in land use for each aquifer's recharge area, a subanalysis on the fraction of recharge areas used as residential, commercial, or with pesticide application was performed. Overall, when fraction of recharge area in residential, commercial, and pesticide categories were combined, a non-significant positive association with breast cancer was found.
Results Comments
Results did not differ when analysis was limited to districts with homogenously mixed well water, to women who were on Cape Cod public water supply for all 16 years, or to non-proxy respondents (i.e. excluding deceased), or when models were adjusted for estimated PCE exposure from drinking water for women who were exposed from improperly prepared distribution pipes. No associations for sum of annual excess nitrate-N, number of years exposed to excite nitrate-N > 1 mg/L.
Author address
Silent Spring Institute, 29 Crafts Street, Newton, MA 02458, USA. brody@silentspring.org
Reviewers Comments
Self-reported information about past drinking water behavior may be unreliable and subject to bias. The authors' subanalysis limited to participants who were more exposed to tap water did not differ from the main analyses. Historical nitrate-N data was available for many years prior to diagnosis (at least 16), making it a suitable indicator of possible wastewater and EDC exposure. The range of exposures was somewhat limited because very few women were either unexposed or exposed at very high concentrations, such that effects of higher exposure cannot be discussed. However, the authors were able to collect extensive risk factor information to use in controlling confounders, addressing the possibility of an ecological fallacy.
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