Evidence From Humans
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PPARgamma and PPARGC1B polymorphisms modify the association between phthalate metabolites and breast cancer risk
Martinez-Nava, G. A., Burguete-Garcia, A. I., Lopez-Carrillo, L., Hernandez-Ramirez, R. U., Madrid-Marina, V., Cebrian, M. E. Biomarkers. 2013. 18:6, 493-501.
Topic area
Environmental pollutant - Genetic variability Phthalates
Study design
Population based case-control
Funding agency
Consejo Nacional de Ciencia y Tecnologia Fondo Sec
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: 220
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Cases were women with histopathologically confirmed breast cancer, ≥ 18 years of age, without prior cancer, >1 year residence in the study area, and were recruited from 17 tertiary hospitals. Matched 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. The full study population included 233 cases and 221 controls, but analysis was restricted to 208 cases and 220 controls with sufficient DNA for genotyping.
Comment about participation selection
Very high reported participation rates of both cases and controls in this population suggest that selection bias is unlikely. Cases and controls all lived in the study area, but because cases were identified at the hospital while controls were identified from a housing list (matched on 'residency'), comparability of cases and controls in socioeconomic position (which is related to risk) and access to diagnosis is unclear.
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 µg/g creatinine for MEP). Because phthalates are rapidly metabolized and excreted, there can be substantial intra-individual variability and single measurements may not capture a stable exposure estimate or correctly rank exposures relevant to disease.
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.
Sociodemographic characteristics; dietary patterns; anthropometric measures; reproductive history (age of menarche, parity, age at first birth, lactation, menopausal status); and age at diagnosis.
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
PPARγ (Pro12Ala) genotype:
Wildtype C carriers, 3rd vs. 1st tertile MEHP (µg/g creatinine): aOR 1.64 (95% CI 1.12-2.41)
Variant G carriers: 3rd vs. 1st tertile MEHP (µg/g creatinine): aOR 0.74 (95% CI 0.23-2.33)
Wildtype C carriers, 3rd vs. 1st tertile MEHHP (µg/g creatinine): aOR 1.80 (95% CI 1.23-2.64)
Variant G carriers: 3rd vs. 1st tertile MEHHP (µg/g creatinine): aOR 0.82 (95% CI 0.25-2.72)

PPARGC1B (Ala203Pro) genotype:
Wildtype G carriers, 3rd vs. 1st tertile MiBP (µg/g creatinine): aOR 0.65 (95% CI 0.43-0.98)
Variant C carriers, 3rd vs. 1st tertile MiBP (µg/g creatinine): aOR: 2.09 (95% CI 0.59-7.34)
Results Comments
MEHP and MEHHP are metabolites of DEHP. MiBP is the metabolite of DiBP. PPARs are nuclear receptor proteins. Because creatinine levels can vary by dietary protein, and diet may be associated with breast cancer, adjusting phthalate measurements for creatinine may introduce bias.
Author address
National Institute of Public Health , Cuernavaca, Morelos , Mexico and.
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