Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Attempts were also made to identify the role and nature of gene-gene and gene-environment interactions in modifying the susceptibility to HNSCC. Polymorphisms in drug metabolizing CYPs or GSTM1 showed modest associations with cancer risk. However, cases carrying haplotypes with variant alleles of both CYP1A1*2A and *2C or CYP1B1*2 and *3 or CYP2E1*5B and *6 were at significant risk of developing HNSCC. Likewise, cases carrying a combination of variant genotypes of CYPs and GSM1 (null) were at higher risk (up to 5-fold) of developing HNSCC. HNSCC risk also increased several-fold in cases carrying variant genotypes of CYPs who were regular tobacco smokers (8-18-fold), tobacco chewers (3-7-fold), or alcohol users (2-4-fold). Statistical analysis revealed a more than multiplicative interaction between combinations of the variant genotypes of CYPs and GSTM1 (null) and between variant genotypes and tobacco smoking or chewing or alcohol consumption, in both case-control and case-only designs. The data thus suggest that although polymorphisms in carcinogen-metabolizing CYPs may be a modest risk factor for developing HNSCC, gene-gene, and gene-environment interactions play a significant role in modifying the susceptibility to HNSCC.
Environ Mol Mutagen 2014 Mar
PMID:Polymorphisms in drug-metabolizing enzymes and risk to head and neck cancer: evidence for gene-gene and gene-environment interaction. 2451 99

The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.
Genet Mol Biol
PMID:GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review. 2911 61