CYP1B1

There are 2 SNPs measured for this gene that predict risk. In the patient, the specific variants are L432V +/- and N453S negative. The commentary below reflects these results.

Health Implications: Cytochrome P450 1B1 is responsible for the 4-hydroxylation of estrogen as well as the activation of common environmental toxins such as polycyclic aromatic hydrocarbons (e.g., products from cigarette smoke, car exhaust, and charbroiled foods), polychlorinated biphenyls (e.g., PCBs), and aflatoxin B1. Polymorphisms convey a higher capacity for induction with toxin exposure, thus greater activation and potential toxicity of these compounds and greater production of 4-hydroxyestrogens.

Hyperinduction can generate oxidative stress and the 4-hydroxyestrogens may convert to quinone compounds that can cause DNA damage in breast tissue. Polymorphisms have been associated with lower 2:16a-hydroxyestrone ratios and increased risk of breast cancer, especially if xenobiotic exposure, high body mass index, long-term HRT, or concomitant CYP1A1 polymorphism. Risk is also increased for cancers of the ovary, prostate, lung and head & neck, especially in smokers.

Minimizing Risk: Do not smoke. Minimize exposure to xenobiotics (e.g., polycyclic aromatic hydrocarbons), also xenoestrogens (e.g., organochlorines), which tend to increase CYP1B1 activity. Eat a diet rich in antioxidants; consider supplementation. Redirect estrogen metabolism away from 4-hydroxylation with cruciferous vegetables and/or agents such as indole 3-carbinol (I3C), diindolymethane (DIM), fish oils or rosemary.

Use caution with long-term HRT, especially conjugated equine estrogens which are preferentially 4-hydroxylated.