Genetically polymorphic xenobiotic metabolizing enzymes are supposed to be host factors for an individual's cancer susceptibility. A total of 255 laryngeal cancer patients was genotyped for NAT1 and NAT2 and compared with 510 reference individuals, matched by age and gender. NAT1 genotypes (NAT1*3, *4, *10, and *11 ) were found equally distributed between cases and control individuals. However, there was a significant overrepresentation of 20 (7.8%) homozygous NAT2 genotypes coding for rapid acetylation (NAT2*4/*4 and NAT2*4/*12A) amongst laryngeal cancer patients versus 19 (3.7%) such individuals in the control group (odds ratio 2.18, 95% confidence limits 1.13, 4.22; P = 0.018). Furthermore, an increasing NAT2*4/*4 frequency in cases with strong cigarette consumption was observed, but also in non-smokers. Heterozygous genotypes of NAT2*4/slow were not overrepresented. These results correspond with earlier findings in lung cancer. Analysis of NAT1 and NAT2 combinations revealed a linkage disequilibrium between NAT1*10 and NAT2*4; NAT1*10 frequency was twofold higher in NAT2*4/*4 carriers than in slow NAT2 coding genotypes. In conclusion, the distinct genotype NAT2*4/*4 proved to be a rare, but powerful host risk factor for larynx carcinoma. These data support the notion that an individual's specific NAT2 genotype may be decisive for the organ of his smoking-initiated cancer.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.
Clin Pharmacol Ther
January 2025
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations.
View Article and Find Full Text PDFA pan-cancer analysis of the oncogenic role of N-acetyltransferase 8 like in human cancer.
Discov Oncol
December 2024
Department of Urology, Yaan People's Hospital, Yaan, China.
Background: N-Acetyltransferase 8 Like (NAT8L) inhibits natural killer (NK)/T-cell cytotoxicity by impairing the formation of the immunological synapse via N-acetylaspartate (NAA). Existing research has predominantly focused on the metabolic functions of NAT8L, particularly in adipose tissues and myelination in the brain. However, in contrast to other N-acetyltransferases such as NAT1 and NAT2, the role of NAT8L in cancer has been less extensively studied.
View Article and Find Full Text PDFSpermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.
Nat Cell Biol
December 2024
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-a key regulator of inflammation and cell death.
View Article and Find Full Text PDFThe Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino--(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes.
Metabolites
August 2024
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
[2,3-diamino--(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), -acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys.
View Article and Find Full Text PDFFunction and expression of N-acetyltransferases 1 and 2 are altered in lymphocytes in type 2 diabetes and obesity.
Biochem Biophys Rep
July 2024
Research Center for Health Sciences and Biomedicine, Autonomous University of San Luis Potosi (UASLP), Mexico.
The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!