Environment and Breast Cancer: Science Review

Evidence From Humans
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Exposure to phthalates and breast cancer risk in northern Mexico
Lopez-Carrillo, L., Hernandez-Ramirez, R. U., Calafat, A. M., Torres-Sanchez, L., Galvan-Portillo, M., Needham, L. L., Ruiz-Ramos, R., Cebrian, M. E. Environ Health Perspect. 2010. 118:4, 539-44.
Topic area
Environmental pollutant - Phthalates
Study design
Population based case-control
Funding agency
National Council of Science and Technology (Mexico
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Analysis stratified by menopausal status
Number of Controls
Controls: 221
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Cases were women with confirmed breast cancer, >18 years of age, without prior cancer, >1 year residence in the study area, and were recruited from 25 tertiary hospitals. Matched healthy controls (1:1 by age +/- 5 years; residence area) were probabilistically selected through a housing list from the general population of seven states in Northern Mexico.
Exposure Investigated
Exposures investigated
Creatinine-corrected urinary concentrations of nine phthalate metabolites, including MEP, MBP, MiBP, MBzP, MCPP, MEHP, MEHHP, MEOHP, and MECP. First morning void urine samples were collected between March 2007 and August 2008, prior to any treatment for c
Exposure assessment comment
The urinary phthalate metabolite concentrations reported here are higher than those reported for females in the general U.S. population (NHANES 2001-2002), with geometric mean concentrations at least one order of magnitude higher in this study population (125 v. 21.7 ug/g creatinine for MEP). A single measurement may not be indicative of cumulative exposure.
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.
Age, age of menarche, parity, menopausal status, other phthalate metabolites.
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
Third tertile vs first tertile (ug/g):
MEP (DEP metabolite): OR 2.20 (95% CI 1.33-3.36)
MEP (DEP metabolite), premenopausal: OR 4.13 (95% CI 1.60-10.7)
MEP (DEP metabolite), postmenopausal: OR 1.84 (95% CI 0.99-3.42)

MBP (DBP metabolite): OR 0.85 (95% CI 0.47-1.57)
MiBP (DiBP metabolite): OR 0.73 (95% CI 0.43-1.24)
MBzP (BBzP metabolite): OR 0.46 (95% CI 0.27-0.79)
MCPP (DOP and others metabolite): OR 0.44 (95% CI 0.24-0.80)

DEHP metabolites:
MEHP: OR 1.23 (95% CI 0.75-2.01)
MEHHP: OR 1.37 (95% CI 0.84-2.24)
MEOHP: OR 0.84 (95% CI 0.52-1.36)
MECPP: OR 1.68 (95% CI 1.01-2.78)
Sum of metabolites: OR 1.41 (95% CI 0.86-2.31)
Results Comments
Because creatinine levels can vary by dietary protein, adjusting phthalate measurements for creatinine may obscure dietary exposures, such as phthalates in packaged meat.
BACKGROUND: Phthalates, ubiquitous environmental pollutants that may disturb the endocrine system, are used primarily as plasticizers of polyvinyl chloride and as additives in consumer and personal care products.Objectives: In this study, we examined the association between urinary concentrations of nine phthalate metabolites and breast cancer (BC) in Mexican women. METHODS: We age-matched 233 BC cases to 221 women residing in northern Mexico. Sociodemographic and reproductive characteristics were obtained by direct interviews. Phthalates were determined in urine samples (collected pretreatment from the cases) by isotope dilution/high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: Phthalate metabolites were detected in at least 82% of women. The geometric mean concentrations of monoethyl phthalate (MEP) were higher in cases than in controls (169.58 vs. 106.78 microg/g creatinine). Controls showed significantly higher concentrations of mono-n-butyl phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(3-carboxypropyl) phthalate (MCPP) than did the cases. After adjusting for risk factors and other phthalates, MEP urinary concentrations were positively associated with BC [odds ratio (OR), highest vs. lowest tertile = 2.20; 95% confidence interval (CI), 1.33-3.63; p for trend < 0.01]. This association became stronger when estimated for premenopausal women (OR, highest vs. lowest tertile = 4.13; 95% CI, 1.60-10.70; p for trend < 0.01). In contrast, we observed significant negative associations for monobenzyl phthalate (MBzP) and MCPP. CONCLUSIONS: We show for the first time that exposure to diethyl phthalate, the parent compound of MEP, may be associated with increased risk of BC, whereas exposure to the parent phthalates of MBzP and MCPP might be negatively associated. These findings require confirmation.
Author address
National Institute of Public Health, Cuernavaca, Morelos, Mexico. lizbeth@insp.mx
Reviewers Comments
This is the first study to show a positive association between DEP and breast cancer and no association (or possible negative association) with other phthalates. The current lack of laboratory evidence of a biological mechanism specifically linking DEP or MEP with breast cancer suggests the possibility that the signal from MEP may be due to another exposure that is correlated with it.