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Polychlorinated biphenyls, cytochrome P450 1A1 (CYP1A1) polymorphisms, and breast cancer risk among African American women and white women in North Carolina: a population-based case-control study
Li, Y., Millikan, R. C., Bell, D. A., Cui, L., Tse, C. K., Newman, B., Conway, K. Breast Cancer Research. 2005. 7:1, R12-8.
Topic area
Environmental pollutant - Organochlorine, PCB
Study design
Nested case-control
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number of Controls
Controls: 599
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Participants of the Carolina Breast Cancer Study. Cases were identified through the North Carolina Central cancer registry. Controls were selected from records of the North Carolina Division of Motor Vehicles, and US Health Care Finance Administration.
Exposures investigated
Lipid-adjusted plasma PCB levels, CYP1A1 polymorphisms M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4)
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
African Americans
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.
Confounding was adequately controlled for.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Yes
Description of major analysis
ORs were calculated using unconditional logistic regression models.
Strength of associations reported
An OR of 2.1 (95% CI: 0.4-10.6) was found for premenopausal white women with high PCB levels and the CYP1A1-m2 polymorphism. The OR was below 1 for postmenopausal white women.

The ORs in this study increased when different exposure cut-points were used.
Abstract
INTRODUCTION: Epidemiologic studies have not shown a strong relationship between blood levels of polychlorinated biphenyls (PCBs) and breast cancer risk. However, two recent studies showed a stronger association among postmenopausal white women with the inducible M2 polymorphism in the cytochrome P450 1A1 (CYP1A1) gene. METHODS: In a population-based case-control study, we evaluated breast cancer risk in relation to PCBs and the CYP1A1 polymorphisms M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4). The study population consisted of 612 patients (242 African American, 370 white) and 599 controls (242 African American, 357 white). RESULTS: There was no evidence of strong joint effects between CYP1A1 M1-containing genotypes and total PCBs in African American or white women. Statistically significant multiplicative interactions were observed between CYP1A1 M2-containing genotypes and elevated plasma total PCBs among white women (P value for likelihood ratio test = 0.02). Multiplicative interactions were also observed between CYP1A1 M3-containing genotypes and elevated total PCBs among African American women (P value for likelihood ratio test = 0.10). CONCLUSIONS: Our results confirm previous reports that CYP1A1 M2-containing genotypes modify the association between PCB exposure and risk of breast cancer. We present additional evidence suggesting that CYP1A1 M3-containing genotypes modify the effects of PCB exposure among African American women. Additional studies are warranted, and meta-analyses combining results across studies will be needed to generate more precise estimates of the joint effects of PCBs and CYP1A1 genotypes.
Author address
Department of Epidemiology, School of Public Heath, University of North Carolina, Chapel Hill, North Carolina, USA. L7S@hsc.mcc.virginia.edu
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