Interindividual Differences in Metabolism of Carcinogens as a Risk Factor for Breast Cancer
Abstract
This study addressed the interaction of environmental and genetic factors in the etiology of breast cancer. Polycyclic aromatic hydrocarbons (PAHs) are metabolically activated to the ultimate carcinogen by the cytochrome P45O isozymes CYP1A1 and CYP1B1. We have investigated the hypothesis that increased expression of CYP1B1 and/or CYP1A1 in breast tissue represents a risk factor for breast cancer. We have determined expression of both CYP1A1 and CYP1B1 genes in histologically normal breast tissue specimens from 36 breast cancer patients and 39 cancer-free individuals. Using a semiquantitative RT-PCR assay we measured CYP1A1 and CYP1B1 expression relative to the constantly expressed Beta-actin gene. We found a large variation in expression of both genes between individuals, and for most samples CYP1B1 transcript levels were 2-7 times higher than CYP1A1. The mean CYP1B1 transcript level in normal breast tissue was 70% higher in breast cancer patients compared with cancer-free controls (p = 0.0473). Genetic polymorphisms in the CYP1A1 and CYP1B1 genes were also analyzed, but no difference in variant frequencies between cases and controls was found. We conclude that CYP1B1 1 is an important PAH-activating enzyme in breast and that high levels can represent a risk factor for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2002
- Accession Number
- ADA404747
Entities
People
- Regine Goth-goldstein
Organizations
- University of California, Berkeley