Laryngeal cancer is known to be associated with smoking and high alcohol consumption. Nucleotide excision repair (NER) plays a key role in repairing DNA damage induced by these exposures and might affect laryngeal cancer susceptibility. In a populationbased case-control study including 248 cases and 647 controls, the association of laryngeal cancer with 14 single nucleotide polymorphisms (SNPs) in 8 NER genes (XPC, XPA, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and RAD23B) was analyzed with respect to smoking and alcohol exposure. For genotyping, sequence specific hybridization probes were used. Data were evaluated by conditional logistic regression analysis, stratified for age and gender, and adjusted for smoking, alcohol consumption and education. Pro-carriers of ERCC6 Arg1230Pro showed a decreased risk for laryngeal cancer (OR 5 0.53, 95% CI 0.34-0.85), strongest in heavy smokers and high alcohol consumers. ERCC5 Asp1104His was associated with risk in heavy smokers (OR 5 1.70, 95% CI 1.1-2.5). Val-carriers of RAD23B Ala249Val had an increased cancer risk in heavy smokers (OR 5 1.6, 95% CI 1.1-2.5) and high alcohol consumers (OR 5 2.0, 95% CI 1.1-3.4). The combined effect of smoking and alcohol intake affected risk, at high exposure level, for ERCC6 1230Pro carriers (OR 5 0.47, 95% CI 0.22-0.98) and RAD23B 249Val carriers (OR 5 2.6, 95% CI 1.3-4.9). When tested for gene-gene interaction, presence of 3 risk alleles in the XPC-RAD23B complex increased the risk 2.1-fold. SNPs in the other genes did not show a significant association with laryngeal cancer risk. We conclude that common genetic variations in NER genes can significantly modify laryngeal cancer risk. ' UICCKey words: genetic variation; population-based case-control study; haplotype; cancer susceptibility; gene-environment interaction Laryngeal cancer is the most frequent form of head and neck cancers in Germany and the second most common form of respiratory tract cancers in the US. 1,2 The average age of onset of the disease is 64 years and it is more common in males than in females (6:1 ratio).Cigarette smoking and alcohol consumption are well acknowledged risk factors for laryngeal cancer. [3][4][5][6][7] Cancer risk is directly related with duration and number of cigarettes smoked, and considerably increased in individuals consuming more than 50 g of alcohol per day. Tobacco smoke contains many carcinogens including a group of N-nitrosamines that produce carcinogenic methyl and pyridyloxobutyl DNA adducts. 8 A further constituent of tobacco smoke is the highly toxic acetaldehyde 9,10 which produces genotoxic 1,N 2 -propano-2 0 -deoxyguanosine DNA adducts. 9,11 Acetaldehyde is also an intermediate product of ethanol metabolism and its concentration increases in a multiplicative manner in individuals who are simultaneously smoking and drinking alcohol. 12 This observation might explain the synergistic and multiplicative effect found for alcohol and smoking in laryngeal cancer risk. 3,7 DNA repair is of fundamental importance in maintaining genomic stabilit...
Inflammation is a multifaceted defense response of immune system against infection. Chronic inflammation has been implicated as an imminent threat for major human malignancies and is directly linked to various steps involved in tumorigenesis. Inflammatory cytokines, interleukins, interferons, transforming growth factors, chemokines, and adhesion molecules have been associated with chronic inflammation. Numerous cytokines are reported to be aberrantly regulated by different epigenetic mechanisms like DNA methylation and histone modifications in tumor tissues, contributing to pathogenesis of tumor in multiple ways. Some of these cytokines also work as epigenetic regulators of other crucial genes in tumor biology, either directly or indirectly. Such regulations are reported in lung, breast, cervical, gastric, colorectal, pancreatic, prostate, and head and neck cancers. Epigenetics of inflammatory mediators in cancer is currently subject of extensive research. These investigations may help in understanding cancer biology and to develop effective therapeutic strategies. The purpose of this paper is to have a brief view of the aberrant regulation of inflammatory cytokines in human malignancies.
Natural antimicrobial agents, particularly essential oils present an excellent alternative to current antibiotics due to their potent and broad-spectrum antimicrobial potential, unique mechanisms of action and low tendency to induce resistance. However their potential as a viable therapeutic alternative is greatly compromised due to their hydrophobic and volatile nature. The objective of the current research was to explore the anti-pathogenic potential of essential oils in a bio-based nano-carrier system. Six different essential oils were tested on multidrug-resistant bacterial pathogens. However, cardamom oil was selected for nano-encapsulation because of most potent anti-microbial activity. Cardamom oil loaded chitosan nano-particles were prepared by ionic gelation method with an encapsulation efficiency of more than 90% and size was estimated to be 50–100 nm. The Zeta potential was more than +50 mV that indicate a stable nano-dispersion. Cytotoxicity analysis indicated non haemolytic and non-cytotoxic behaviour on human corneal epithelial cells and HepG2 cell lines. Cardamom oil loaded chitosan nano-particles were found to exhibit excellent anti-microbial potential against extended spectrum β lactamase producing Escherichia coli and methicillin resistant Staphylococcus aureus. Our results suggested safety and efficacy of cardamom oil loaded chitosan nano-particles for treating multidrug-resistant pathogens hence offer an effective alternative to current antibiotic therapy.
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