Cigarette smoking, polychlorinated biphenyls, CYP1A1 polymorphisms and breast cancer among African-American and white women in North Carolina

The effects of cigarette smoking and PCBs on breast cancer risk remain controversial. As a part of the Carolina Breast Cancer Study (CBCS), this study was designed to evaluate the risk for breast cancer from exposure to cigarette smoking and PCBs in relation to CYP1A1 genotypes. We examined CYP1A1 genotype frequencies, main effects of variant alleles of CYP1A1 gene, and joint effects of cigarette smoking as well as PCBs and polymorphisms of CYP1A1 on breast cancer risk. Ignoring smoking status and plasma PCBs, no associations were observed for CYP1A1 variant-containing genotypes and breast cancer. Women with one or more M1 alleles had a positive association between breast cancer and former smoking, and the association was stronger for women who quit smoking 10 years or less prior to interview. A positive association was also found among women with the M1 allele who smoked for 20 years or more and who started smoking before the age of eighteen. African-American women with one or more M3 alleles showed a positive association among former smokers who quit smoking within the past 10 years and women who smoked for 20 years or more. There was no evidence of strong joint effects between CYP1A1 M1-containing genotypes and total PCBs in African-American or Caucasian women. Statistically significant multiplicative interactions were observed between CYP1A1 M2-containing genotypes and elevated plasma total PCBs among Caucasian women. Multiplicative interactions were also observed between CYP1A1 M3-containing genotypes and elevated total PCBs among African-American women. Further study of biological mechanisms of the interactions between the CYP1A1 polymorphisms and cigarette smoking as well as PCBs on breast cancer risk is warranted.