In vitro, using a panel of cultured human lung cells, we found hypermethylation of the CYP1A1 enhancer in cancer cell lines and an inverse correlation between DNA methylation and mRNA levels (Spearman r = -0.53; p = 0.003).
The extraction method was combined with newly designed PCR-based assays for cancer susceptibility marker genes such as CYP1A1 (exon 7), CYP2E1 (Dra1, Rsa1), GSTM1 and NAT2 [NAT2*5A (C481T), NAT2*6A (G590A), NAT2*7A (G857A)].
The role of these genetic polymorphisms in cancer susceptibility has been most extensively evaluated for isozymes of cytochrome P450 (CYP1A1, CYP2D6, and CYP2E1), N-acetyltransferase (NAT1 and NAT2), glutathione S-transferase (GSTM1, GSTT1, and GSTP1), microsomal epoxide hydrolase, and NAD(P)H:quinone oxidoreductase.
Recent clinical studies suggest a relationship between high AHH activity and lung cancer associated with cigarette smoking (Kouri, R.E., McKinney, C.E., Slomiany, D.J., Snodgrass, D.R., Wray, N.P., and McLemore, T.L.Cancer Res.42: 5030-5037, 1982).
Recently a CYP1A1 MspI polymorphism at the 3'-flanking region of the gene has been found to be associated with smoking related cancer risk and may, therefore, also be associated with vascular disease.
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.
The genotype distribution of CYP1A1*1 in cancer patients was 6% for homozygous (CYP1A1 M1 [C/C], 34% for heterozygous CYP1A1 M1 [T/C] and 60% for wild type (CYP1A1 M1 [T/T] (OR: 0.583, CI-95% (0.252-1.348).
The frequency of cancer-associated m2m2- (C-) genotype of CYP1A1 and the factors contributing to the increased CYP1A1 expression in gastric cancers (GCs) are largely unknown.
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.
The study reveals active CYP1 overexpression in human tumors and uncovers the potential use of CYP1 enzymes and mainly CYP1B1 as targets for cancer therapy.
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.
Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: a correlation with family histories of cancer.
Khellinoflavanone, a Semisynthetic Derivative of Khellin, Overcomes Benzo[<i>a</i>]pyrene Toxicity in Human Normal and Cancer Cells That Express CYP1A1.
To investigate the prevalence of CYP1A1 and GSTM1, and their association with increased risk of lung carcinoma in Chinese, allele-specific PCR and multiplex PCR technique were employed to identify the genotypes of CYP1A1 and GSTM1 in a case-control study of 106 lung carcinoma patients with histopathological diagnosis and 106 matched controls free ofmalignancy in Jiangsu Province, China.
The distribution of CYP1A1, CYP2E1 and XRCC1 gene polymorphisms in the Basilicata population is not different from that of other Italian regions or from that reported in the literature for Caucasian populations, and polymorphisms in these genes do not play an important role in determining cancer risk in the population under study.
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.
We here summarize the current knowledge on CYP1A1 as a key player in the metabolism of exogenous and endogenous substrates and as a promising target molecule for prevention and treatment of human malignancies.
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).
In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01).