PURPOSE: Interindividual genetic differences in susceptibility to chemical carcinogens are one of the most important host factors in human cancer. The genetically determined differences in metabolism, related to cytochrome P450 (CYP450) genes have been reported to be associated with various cancer susceptibility. The present study was set up to establish the frequency of the polymorphic genotypes of two CYP450 (CYP2E1/PstI and CYP2E1/DraI) isozymes in Korea, to evaluate a possible increased incidence of the genotype associated with higher cervical cancer risks among Korean cervical cancer patients. MATERIALS AND METHODS: In this study, extracted DNAs from 228 cervical cancer patients and 360 normal healthy controls were analysed with the polymerase chain reaction-restriction fragment length polymosphism (PCR-RFLP) method. RESULTS: In the CYP 2E1 genotypes, detected by PstI or RsaI digestion, there were no statistically remarkable differences between the cervical cancer patients and control groups. And when the cervical cancer patients were divided into subgroups with respect to the age, the frequency of CYP 2E1/PstI polymorphisms in the cervical cancer patients under the 40 years old was not significantly higher compared to the controls or the patients above the 40 years old and, c1/c1 genotype was prominent in this type of polymorphism. The frequency of CYP 2E1/DraI polymorphisms in the cervical cancer patients was not significantly higher compared to the controls, and D/D genotype was prominent in this type of polymorphism. In cervical carcinoma, the polymorphic genotypes of CYP 2E1 were not correlated to other parameters including clinical stage, histological tumor type, and degree of differentiation. CONCLUSION: These results suggest that individuals carrying CYP 2E1/PstI (c1/c1) or CYP 2E1/DraI (D/D) alleles are not genetically susceptible to cervical cancer in Korea.
Adult ; Alleles ; Carcinogens ; Cytochrome P-450 CYP2E1* ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Digestion ; DNA ; Genetic Predisposition to Disease* ; Genotype ; Humans ; Incidence ; Isoenzymes ; Korea ; Metabolism ; Uterine Cervical Neoplasms*

Background/Aims: Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition. Methods: We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes. Results: Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae. Conclusions This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.