Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women.
BACKGROUND
Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer.


METHODS
We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4)


RESULTS
No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2-3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9-1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9-7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8-2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes.


CONCLUSIONS
Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak.
Li
Yu
Y
Department of Epidemiology, School of Public Heath and Lineberger Comprehensive Cancer Center, School of Medicine, 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
D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D017720:Molecular Epidemiology / Q000379:methods*; D009657:North Carolina / Q000453:epidemiology / Q000208:ethnology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods; D012907:Smoking / Q000235:genetics*; D044465:White People / Q000235:genetics*
D005819:Genetic Markers; D019363:Cytochrome P-450 CYP1A1