Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

Implicit bias against the Romas in Hungarian healthcare: taboos or unrevealed areas for health promotion?

The Roma or Gipsy population is the largest ethnic minority both in Europe and Hungary with a 10-15 years lower life expectancy and significantly worse health indicators than majority populations. The purpose of this exploratory study was to investigate a sensitive and controversial topic: the perspectives of healthcare staff about the presence and impacts of implicit bias in the Hungarian healthcare system towards Roma patients. Therefore, between June 2017 and May 2018 semi-structured interviews were conducted involving 13 healthcare professionals. Interview transcripts were coded and thematically analysed. The presence and occasional manifestation of prejudices against the Romas were noted by the interviewees, most commonly in the form of longer waiting time, comments or other meta-communicative tools. Study participants appeared to exclude a direct relationship between health providers' implicit bias and the lower quality of health services or the worse health status of Roma patients. However, as reported, indirect negative effects may occur in cases where a patient refrains from seeking care due to previous perceived or experienced discrimination. As barriers to effective patient-provider communication and cooperation, differences in culture, health-seeking behaviour and gaps between health literacy levels were emphasized. In terms of prevention, enhancing anti-discriminatory attitudes from early childhood within the families, the role of media in conveying unbiased information, increasing health awareness of the Roma people as well as educating healthcare providers on culture-related issues may be beneficial. Stress and burnout of healthcare professionals also need to be addressed as these may impact on the enactment of unconscious biases.

Prejudices and their healthcare implications. Lessons learnt from a national survey. / [Eloítéletek és hatásaik az egészségügyi ellátásban. Egy felmérés tanulságai].

Introduction: The presence and recognition of prejudice during care were examined among healthcare professionals towards the Roma population, the largest ethnic minority in Hungary. Aim: The aim of this study was to explore the extent to which prejudice in the Hungarian healthcare system might affect the quality of care and, thereby, the health of the Roma patients. Method: Semi-structured interviews were conducted between June 2017 and May 2018 with 13 interviewees. Qualitative methods were applied to analyse the transcripts. Results: Our respondents generally confirmed the presence of prejudices in the healthcare system. Prejudicial attitudes and discriminatory behaviour are less common in wards where the prevalence of disadvantaged patients (HIV-positive, homeless) is high (e.g., infectology). Prejudice is not specifically directed at the Roma ethnic minority, but also extends to populations living under poor socio-economic conditions, or with underlying self-destructive behaviour (alcoholism, drug use). In the opinion of our interviewees, occasional prejudicial behaviour does not lead to sub-standard care, but, on the contrary, to positive discrimination. Prejudice does not directly lead to poorer health, but it cannot be ruled out that it may indirectly contribute to it, in the case if the patient does not seek medical attention due to a former negative experience within healthcare. Conclusion: Our results confirmed the occasional presence of prejudice against the Romas in the healthcare system, however, this may not directly contribute to Romas' poorer health status. Our results also highlighted the importance of prevention, including the education of both parties and the prevention of the burnout of care providers. Orv Hetil. 2020; 161(19): 789-796.

Association of pre-miR-146a rs2910164 polymorphism with the risk of head and neck cancer.

BACKGROUND: Over- or underexpression of miR-146a has been reported in several different human tumor types, and a polymorphism in its precursor form (pre-miR-146a rs2910164 G/C) has been recently studied in connection with cancer susceptibility. The aim of the present study was to investigate the possible influence of the pre-miR-146a rs2910164 polymorphism on the risk of squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: The study included 468 patients with HNSCC and 468 cancer-free, age-, gender-, and smoking-matched controls. The miR-146a genotypes were determined using polymerase chain reaction with confronting two-pair primers, and their distribution was compared by multivariate binary logistic regression analysis. RESULTS: Occurrence of heterozygous (odds ratio, OR=1.46, 95% confidence interval, CI=1.10-1.95, p=0.009) and C/C homozygous (OR=2.37, 95% CI=1.01-5.60, p=0.048) individuals was significantly more frequent among patients with HNSCC than in the control group. CONCLUSION: The pre-miR/146a C allele may contribute to an increased susceptibility to HNSCC.

Effect of glutathione-S-transferase M1 and T1 allelic polymorphisms on HPV-induced cervical precancer formation.

AIM: The effect of GSTM1 and GSTT1 allelic polymorphisms was studied on the HPV-induced cervical carcinogenesis. PATIENTS AND METHODS: Two hundred and fifty-three women with persistent high-risk HPV infection were involved in the study; 117 of them developed cervical high-grade dysplasia and/or cervical intraepithelial neoplasia grade III during the 7-year follow-up period. Occurrence of GSTM1 and GSTT1 null genotypes was compared between women with and without dysplasia. RESULTS: Presence of GSTM1 (OR=1.78, 95% CI=1.06-2.97; p=0.028) and GSTT1 (OR=1.89, 95% CI=1.10-3.26; p=0.022) null genotypes was statistically significantly more frequent among women with cervical dysplasia than in the group without dysplasia. Participants with dual null genotype had an even more elevated risk of precancerous lesion (OR=2.35, 95% CI=1.17-4.73; p=0.017). CONCLUSION: Our study demonstrated the role of both GSTM1 and T1 null genotypes in the development of high-grade cervical dysplasia in a Caucasian population.

Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer.

BACKGROUND: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. RESULTS: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). CONCLUSION: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy.

Association between allelic polymorphisms of metabolizing enzymes (CYP 1A1, CYP 1A2, CYP 2E1, mEH) and occurrence of colorectal cancer in Hungary.

BACKGROUND: Genetic polymorphisms of metabolizing enzymes may affect the risk of cancer formation in humans. Since the diet can contain polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs), the relationship between polymorphisms of enzymes involved in PAH and HA metabolism and the occurrence of sporadic colorectal cancer was studied. PATIENTS AND METHODS: Five hundred colorectal cancer patients and 500 controls were genotyped for cytochrome P450 enzymes (CYP) 1A1 Ile/Val, CYP 1A2*1F, CYP 2E1 c1/c2, microsomal epoxy hydrolase (mEH) exon 3 Tyr113His and exon 4 His139Arg polymorphisms by allele-specific polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). RESULTS: The presence of CYP 1A1 Val, CYP 2E1 c2 and mEH exon 3 His alleles was statistically significantly associated with the occurrence of colorectal cancer (OR: 1.44 95% CI: 1.04-2.00; OR: 1.74 95% CI: 1.15-2.65; OR: 1.79 95% CI: 1.10-2.92, respectively). CONCLUSION: These findings suggest that allelic polymorphism of metabolizing enzymes play an important role in human colorectal carcinogenesis by affecting the metabolism of dietary carcinogens.

Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferase enzymes and susceptibility to colorectal cancer.

BACKGROUND: Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) are involved in the metabolism of a wide range of carcinogenic chemicals. Allelic polymorphism of these enzymes is associated with variations in enzyme activity, hence it may affect the concentration of activated carcinogenic chemicals in the body. Previous studies suggest a possible cancer risk-modifying effect of these allelic polymorphisms, but the results are still controversial. We evaluated the effect of GSTM1, GSTT1, GSTP1, NAT1 and NAT2 enzymes on individual susceptibility to colorectal cancer, with particular attention to possible interactions between the studied genotypes. MATERIALS AND METHODS: Five hundred colorectal cancer patients and 500 matched cancer-free controls were included in the study. The allelic polymorphisms of GSTM1, GSTT1 and GSTP1, NAT1 and NAT2 enzymes were determined by PCR-based methods, from peripheral blood leukocytes, and allelic distributions were compared between colorectal cancer patients and controls. RESULTS: The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92) and rapid acetylator genotypes of NAT2 (OR: 1.52, 95% CI: 1.17-1.98) were associated with an elevated risk No statistically significant correlation between NAT1, GSTT1, GSTP1 genotypes and colorectal cancer was found. Remarkably increased risk was associated with the GSTM1 0 allele--NAT2 rapid acetylator genotype combination (OR: 2.39, 95% CI: 1.75-3.26) and with the GSTM1 0 allele--NAT2 and NAT1 rapid acetylator triple combination (OR: 3.28, 95% CI: 2.06-5.23). Carrying 4 or 5 putative "high-risk" alleles substantially increased the risk of colorectal cancer (OR: 3.69, 95% CI: 2.33-5.86). CONCLUSION: The genotype of certain metabolizing enzymes affects the risk for colorectal cancer. This effect is particularly important when certain allelic combinations are studied. In the near future, individual level risk assessment may be reached by further increasing the number of studied polymorphisms, combining them with traditional epidemiological risk factors.