Cytochrome P450

Cytochrome P450 and Cancer

Cytochrome P450 enzymes are involved in the removal of carcinogenic compounds from the body. However, in some cases they can also activate compounds consumed in food, converting procarcinogens to carcinogens. In addition, several cancers are sensitive to hormone concentrations, such as the link between breast cancer and oestrogen levels. CYP proteins involved in steroid or retinoic acid metabolism could promote or suppress tumour development through hormonal control. Genetic variability could play a role if a polymorphism affected a CYP protein involved in such processes.

Certain CYP allelic variants are considered biomarkers for cancer susceptibility, several of which influence the bioactivation of carcinogens. For example, CYP1B1 plays an important role in the bioactivation of carcinogens in different cancer types. CYP1B1 is highly expressed in mammary, ovary and uterus tissue, where it catalyses the 4-hydroxylation of estradiol, which can generate free radicals that cause cellular damage. The local formation of CYP1B1 is thought important for beast and endometrial carcinogenesis, and the polymorphic variant CYP1B1*3/*3 appears to be associated with increased breast cancer risk, especially when combined with hormone replacement therapy (HRT).

CYP1B1 is also implicated in tobacco smoke-related cancers in several organs. Tobacco smoke contains several procarcinogens, including polycyclic aromatic hydrocarbons (PAHs), nitrosamines and arylamines. PAHs can be activated into carcinogens by CYP1A1, CYP1A2 and CYP1B1. In addition, certain PAHs can inhibit the activity of CYP1A2 and CYP1B1, which can affect their own metabolism as well as the metabolism of other carcinogens catalysed by these CYP proteins. PAHs can be activated within the urothelium (lining of the ureters, bladder and urethra), where CYP1B1 is present, and tobacco smoking is the major cause of urinary bladder cancer. Tobacco smoking is also a major cause of head and neck cancers, and the polymorphic variant CYP1B1*3/*3 appears to increase a smoker’s susceptibility to these cancers.

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