We estimated the frequency of CYP1A1, CYP1A2, CYP1B1, CYP19, and SULT1A1 allelic variants in a female population of the Novosibirsk district and their association with the elevated risk of breast (BC), ovarian (OC), and endometrial (EC) cancers. Significant differences (OR = 2.34, p = 0.0002) in the allele distributions for CYP1A1 M1 polymorphism between patients with BC (n = 118) and controls (n = 180) were found. No significant difference in both genotype and allele distributions for CYP1A1 polymorphisms in patients with OC (n = 96) and EC (n = 154) was observed. Remarkable differences in the allele and genotype distributions for CYP1A2*1F polymorphism in patients with BC or OC were found (OR = 0.26, p = 0.0000005 and OR = 0.34, p = 0.00000002). There were no differences for this polymorphism in women with EC. In patients with BC no significant differences were found in genotype and allele distributions for R264C polymorphism in the CYP19 gene. The frequency of a mutant CYP19 heterozygote genotype C/T was higher in patients with OC and EC compared with healthy women (OR = 3.87, p = 0.001 and OR = 3.73, p = 0.0004, respectively). Comparison of allele frequencies revealed a deficiency of an allele A of SULT1A1*2 in patients with OC (OR = 0.64, p = 0.019) compared with controls. No differences were found in the genotype and allele distributions for SULT1A1 polymorphism between patients with BC and EC and controls. In addition, there were no difference in allele and genotype distributions for CYP1B1 119G-->T polymorphism between BC and control. In conclusion, these results support the hypothesis that susceptibility gene alleles of estrogen-metabolizing enzymes may differentially influence risk for woman hormone-dependent cancers.
Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (Aromatase) and II-phase enzyme Sulfotransferase (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated a frequency of these allelic variants in the female Caucasian population of the Novosibirsk region of Russia and their association with the elevated risk of ovarian and endometrial cancer. A DNA bank of gynecologic oncology patients, patients with benign gynecologic diseases and healthy women was created, and the following single nucleotide polymorphisms (SNPs) were examined: CYP1A1 M1 polymorphism, that is, T264-C transition in the 3 0 -noncoding region; CYP1A2*1F polymorphism, that is, C734-A transversion in CYP1A2 gene; C-T transition (Arg264Cys) in exon 7 of CYP19; SULT1A1*2 polymorphism, that is, G638-A transition (Arg213His) in SULT1A1 gene. A positive correlation of C allele of CYP1A2*1F and G allele of SULT1A1*2 with hormone-dependent cancers in women was found. Thus, these genes are appropriate candidates for studying the contribution of genetic factors to endocrine disorder and environmentally determined diseases susceptibility. In contrast, no association of CYP19 and CYP1A1 polymorphisms with increased cancer risk was revealed.
Background: Platinum-based chemotherapy, cisplatin (DDP) specifically, is the main strategy for treating lung cancer (LC). However, currently, there is a lack of predictive drug-resistance markers, and there is increased interest in the development of a reliable and sensitive panels of markers for DDP chemotherapy-effectiveness prediction. MicroRNAs represent a perspective pool of markers for chemotherapy effectiveness. Objectives: Data on miRNAs associated with LC DDP chemotherapy response are summarized and analyzed. Materials and methods: A comprehensive review of the data in the literature and an analysis of bioinformatics resources were performed. The gene targets of miRNAs, as well as their reciprocal relationships with miRNAs, were studied using several databases. Results and Discussion: The complex analysis of bioinformatics resources and the literature indicated that the expressions of 12 miRNAs have a high predictive potential for LC DDP chemotherapy responses. The obtained information was discussed from the point of view of the main mechanisms of LC chemoresistance. Conclusions: An overview of the published data and bioinformatics resources, with respect to the predictive microRNA markers of chemotherapy response, is presented in this review. The selected microRNAs and gene panel have a high potential for predicting LC DDP sensitiveness or DDP resistance as well as for the development of a DDP co-therapy.
Disturbed cervicovaginal-microbiome (CVM) structure promotes human papillomavirus (HPV) persistence and reflects risks of cervical lesions and cancer onset and recurrence. Therefore, microbiomic biomarkers may be useful for cervical disease screening and patient management. Here, by 16S rRNA gene sequencing and commercial PCR-based diagnostic kits, we profiled CVM in cytological preparations from 140 HPV-tested women (from Novosibirsk, Russia) with normal cytological findings, cervical lesions, or cancer and from 101 women who had recently received different cancer therapies. An increase in lesion severity was accompanied by higher HPV prevalence and elevated CVM biodiversity. Post-treatment CVM was found to be enriched with well-known microbial biomarkers of dysbiosis, just as in cervical disease. Nonetheless, concentrations of some skin-borne and environmental species (which gradually increased with increasing lesion severity)—especially Cutibacterium spp., Achromobacter spp., and Ralstonia pickettii—was low in post-treatment patients and depended on treatment types. Frequency of Lactobacillus iners dominance was high in all groups and depended on treatment types in post-treatment patients. Microbiome analysis via PCR-based kits revealed statistically significant differences among all groups of patients. Thus, microbiome profiling may help to find diagnostic and prognostic markers for management of cervical lesions; quantitative PCR-based kits may be suitable for these purposes.
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