Aryl hydrocarbon hydroxylase activity in lymphoblasts from normal Finnish adults and from patients with pulmonary carcinomas and other types of malignancy has been studied by a modification of previously used techniques.
Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: a correlation with family histories of cancer.
A case-control study involving 750 cases with squamous-cell carcinoma of the head and neck (HNSCC) and an equal number of healthy controls was initiated to investigate the association of polymorphisms in the drug metabolizing genes cytochrome P450 1A1 (CYP1A1), CYP1B1, CYP2E1 and glutathione S-transferase M1 (GSTM1) with the risk of developing cancer.
A thymine/cytosine point mutation in the MSP I restriction site of cytochrome P450 1A1 (CYP1A1) has been linked to susceptibility to smoking-related cancers and is reported to result in increased enzyme activity.
An association between risk and the CYP1A1 polymorphism has been noticed for several cancers, and the GSTM1 gene is one of the most extensively studied genes concerning polymorphism and cancer risk.
Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility.
Data on lung cancer and CYP1A1 gene polymorphism indicate that carriers of genotypes associated with CYP1A1 inducibility are at higher risk for cancer, but that, at least for Caucasians, the recognized mutations probably identify only a fraction of the inducible individuals.
From this it is concluded that Ya gene activation by planar aromatic compounds involves metabolism of these inducers by the phase I xenobiotic-metabolizing cytochrome P1-450 system into electrophilic compounds, which is consistent with a recently proposed model [Prochaska, H. J.& Talalay, P. (1988) Cancer Res.48, 4776-4782].
Furthermore, silencing CYP1A1 and subsequently downregulating hTERT resulted in the reduction of cancer cell viability by more than 40%, which appeared as early as 24 hours after the treatment.
Genetic polymorphisms of cytochrome p450 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes are thought to have significant effects on the metabolism of environmental carcinogens and thus on cancer risk, but the reported results are not always consistent.
Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer.
However, a full evaluation of an association between CYP1A1*2A and cancer susceptibility in Europeans is difficult and will require a larger number of participants.
However, because of the difference in cancer risks between the DT (9.3 cases per 1000 person years) and the GPT (5.3 cases), the analytical cohort was stratified by trial; the DT participants who were heterozygous or homozygous for the variant-allele at CYP1A1*2A had a reduced risk for developing GCC (adjusted RR (95% CI) 0.47 (0.23-1.00) p = 0.037).