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.
BACKGROUND
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.
Li
Yu
Y
Department of Epidemiology, School of Public Heath, University of North Carolina, Chapel Hill, North Carolina, USA. L7S@hsc.mcc.virginia.edu
Millikan
Robert C
RC
Bell
Douglas A
DA
Cui
Lisa
L
Tse
Chiu-Kit J
CK
Newman
Beth
B
Conway
Kathleen
K
D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000506:poisoning*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000506:poisoning*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*; D001741:Black or African American
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1