Proposal for screening of oral and oropharyngeal cancer in the population at risk

The aim of our proposal is to suggest selected screening for people, who are the most likely candidates for the development of head and neck cancer. The screening organized by the family physicians on their own database in collaboration with the local dentists or ENT doctors involves examination and health education by effective communication and written information about risk of cancer and early signs and symptoms of the disease.     

Prevalence of URAT1 allelic variants in the Roma population

ABSTRACT

The Roma represents a transnational ethnic group, with a current European population of 8–10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians. However, RHUC 1 patients have been described in a variety of ethnic groups (e.g., Arab Israelis, Iraqi Jews, Caucasians, and Roma) and in geographically noncontiguous countries. This study confirms our previous findings regarding the high frequency of SLC22A12 variants observed. Frequencies of the c.1245_1253del and c.1400C>T variants were found to be 1.92% and 5.56%, respectively, in a subgroup of the Roma population from five regions in three countries: Slovakia, Czech Republic, and Spain. Our findings suggested that the common dysfunction allelic variants of URAT1 exist in the general Roma population and thus renal hypouricemia should be kept in differential diagnostic algorithm on Roma patients with defect in renal tubular urate transport. This leads to confirm that the genetic drift in the Roma have increased the prevalence of hereditary disorders caused by very rare variants in major population.     

A newly discovered founder population: the Roma/Gypsies

The Gypsies (a misnomer, derived from an early legend about Egyptian origins) defy the conventional definition of a population: they have no nation-state, speak different languages, belong to many religions and comprise a mosaic of socially and culturally divergent groups separated by strict rules of endogamy. Referred to as "the invisible minority", the Gypsies have for centuries been ignored by Western medicine, and their genetic heritage has only recently attracted attention. Common origins from a small group of ancestors characterise the 8-10 million European Gypsies as an unusual trans-national founder population, whose exodus from India played the role of a profound demographic bottleneck. Social and economic pressures within Europe led to gradual fragmentation, generating multiple genetically differentiated subisolates. The string of population bottlenecks and founder effects have shaped a unique genetic profile, whose potential for genetic research can be met only by study designs that acknowledge cultural tradition and self-identity.     

Increased prevalence of the CVD-associated ANRIL allele in the Roma/Gypsy population in comparison with the majority Czech population

Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P < 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

Changing cytologic detection rates for cervical intraepithelial neoplasia and invasive cancer in a population lacking a mass screening program

The secular trends in the detection rates for cervical intraepithelial neoplasia (CIN) and invasive carcinoma were evaluated for a population lacking a mass screening program. For the period from 1980 through 1987, 185,659 Papanicolaou smears from 176,511 women were examined. The average annual age-adjusted detection rate for invasive cervical cancer declined from 3.7 x 10(-3) in 1980 to 1.4 x 10(-3) in 1987. The rate of cytologic findings consistent with CIN 3 and verified by histology increased from 0.7 x 10(-3) to 2.6 x 10(-3), and the rate of findings consistent with CIN 1 and CIN 2 increased from 4.3 x 10(-3) to 7.2 x 10(-3). The yield of Papanicolaou smear diagnoses consistent with CIN 3 was substantial (more than one case per 1,000) for women up to 60 years old, but was insignificant for older women.     

Calcaneous ultrasonographic assessment of bone mineral density in the Roma minority population of Croatia--preliminary report

A multidisciplinary anthropological and epidemiological pilot field study of the Bayash population living in 6 villages of the eastern Croatian region of Baranya has been performed in 2005/06. The Bayash (or Boyash) belong to the Roma minority population speaking a distinct archaic dialect of the Romanian language. Since the bone mineral density values in the Roma have not been explored so far and the prevalence of osteoporosis is unknown for this ethnic minority group a screening by means of the Sahara Hologic clinical bone sonometer has been performed on 232 voluntary participants (73 males and 159 females). The prevalence of osteoporosis (T-score <-2.5) in the Bayash aged 50 and older is found to be 9.1% in males and 34.4% in females, which is substantially higher than in the general population of Croatia. The prevalence of T-values ranging from -1 to -2.5 indicating osteopenia is found to be 63.6% in males and 45.3% in females, while T-values within the normal range are found only in 27.3% males and 20.3% females. In addition to the low bone mass in older subjects, the mean estimated bone mineral density in all age groups of Bayash men and women was lower in comparison to the manufacturer's reference ranges for European population of the same age. Since body size effects could not be declined, the reference values that would be appropriate for the Roma population should be further explored. The high estimated prevalence of developed osteoporosis calls for attention and the survey should also be extended to exploring the association of low bone mineral density with particular life style and reproductive factors present in this semi-sedentary Roma population.     

Traditional CVD risk factors and socio-economic deprivation in Roma minority population of Croatia

Researches into health inequalities consistently show disadvantages in health status, morbidity and mortality for various ethnic minority groups. Current knowledge about prevention of cardiovascular diseases (CVD) mainly derives from studies carried out in populations of European origin while the evidences involving Roma population are scarce. Roma, an ethnic minority of northern Indian origin, live in many countries throughout the world and are well known for preserved traditions and resistance to assimilation. They are most often marginalized economically, spatially, politically and in terms of culture. In order to assess the health status and health-related lifestyle attributes, a multidisciplinary anthropological and epidemiological community-based study was carried out including a total of 423 members of the Bayash Roma minority population living in two regions of Croatia (144 men and 279 women, aged 18-84 yrs). Hypertension (HT) was found in 24.8% Bayash Roma (21.5% men and 26.5% women) using standard diagnostic criteria (i.e. BP > or = 140/90 mm Hg or taking antihypertensive therapy). The prevalence increases from 5.9% in the age group 18-34 yrs; 35.0% in the age group 35-64 yrs, and 51.4% in the age group 65+ yrs. The prevalence of hypertension in the Bayash Roma is almost half of the magnitude of what is usually reported for the general population of Croatia. It is also lower when compared with other European populations and this finding is not due to comparatively younger average age of the Bayash sample. The significant association of hypertension with age and BMI was confirmed in this study and the importance of non-traditional SES-related CVD risk factors was highlighted. Smoking is a part of traditional Roma life-style and with 70% of smokers almost the entire population is equally exposed to this risk factor in their family environment. Since homogenously distributed, this risk factor did not show to be a significant predictor of hypertension. The extent to which hypertension is influenced by traditional CVD risk factors as well as by some SES indicators was also assessed using a forward stepwise method of the multivariate logistic analysis. Each risk factor was explored as quantitative variable as well as qualitative one using various cut-offs. The best model showed to be the one having age and BMI presented as quantitative variables and sex, region, smoking status, income and schooling years as categorical ones; with cut-off 3 for number of income sources and 8 for the number of schooling years. In spite of the low prevalence of hypertension, the presented results are showing that Bayash Roma are bearing a high CVD risk factors load. We expect that with westernization of their life-style and along with increase of the economic power, the proportion of CVD in population of Bayash Roma will also increase. Therefore, it is important to recognize the need for early cardiovascular disease risk factors prevention in this minority population.     

High prevalence of CYP2C19*2 allele in Roma samples: study on Roma and Hungarian population samples with review of the literature

The purpose of our study was to characterise the CYP2C19*2 and CYP2C19*3 alleles in healthy Roma and Hungarian populations. DNA of 500 Roma and 370 Hungarian subjects were genotyped for CYP2C19*2 (G681A, rs4244285) and CYP2C19*3 (G636A, rs4986893) by PCR–RFLP assay and direct sequencing. Significant differences were found comparing the Roma and Hungarian populations in CYP2C19 681 GG (63.6 vs. 75.9 %), GA (31.8 vs. 23.0 %), AA (4.6 vs. 1.1 %), GA+AA (36.4 vs. 24.1 %) and A allele frequencies (0.205 vs. 0.125) (p < 0.004). Striking differences were found between Roma and Hungarian samples in CYP2C19*1 (79.5 vs. 87.4 %) and CYP2C19*2 (20.5 vs. 12.6 %) alleles, respectively (p < 0.001). None of the subjects was found to carry the CYP2C19*3 allele. Frequencies of the intermedier metabolizer phenotype defined by the *1/*2 genotype (0.318 vs. 0.230, p < 0.005) and poor metabolizer predicted by the *2/*2 genotype (0.046 vs. 0.011, p < 0.005) was significantly higher in Roma than in Hungarians, respectively. Genotype distribution of the Roma population was similar to those of the population of North India, however, a major difference was found in the frequency of the CYP2C19*2 allele, which is likely a result of admixture with European lineages. In conclusion, the frequencies of the CYP2C19 alleles, genotypes and corresponding extensive, intermediate and poor metabolizer phenotypes studied here in the Hungarian population are similar to those of other European Caucasian populations, but display clear differences when compared to the Roma population.     

A BASIC program for use in teaching population dynamics

This interactive simulation model can be used to demonstrate population growth with discrete or overlapping generations and the effects of random, constant, or density-dependent mortality.     

Age trends in prevalence of cardiovascular risk factors in Roma minority population of Croatia

The Roma (Gypsy) are the largest European minority population characterized by poverty, social exclusion as well as by numerous life-style and cultural specificities, which all could have an adverse impact on their cardiovascular health. This study assesses the prevalence of cardiovascular diseases (CVD) risk factors in community-based sample of 430 adult Roma, living in rural area of Croatia, by providing the actual and age-adjusted estimates using the European standard population. The most prominent classical CVD risk phenotypes (blood pressure, obesity, smoking, glucose and lipid profile) were selected, and the standard risk cut-offs were applied. The study has shown that compared to general population of Croatia, the Roma population bears a high CVD risk factors load related to smoking and high glucose level. The CVD risk factors prevalence in Roma also showed important sex and age patterns, the most imposing of which are the findings of higher prevalence of CVD risks in women (especially obesity and triglyceride levels) and the trend of higher body mass index (BMI) level in younger age group (18–34 years) which both stand in contrast to the trends characterizing the general population of Croatia. These findings are complemented by the trend of decreased risk in the oldest age group (65+ years) for all investigated CVD risk factors (with exception of triglycerides level) compared to the 50–64 age group. We conclude that the age and sex CVD risks pattern point to the health transition of this rural Roma population. As we expect the proportion of CVD in the Roma minority of Croatia to increase in the future along with further modernization of their lifestyle, the CVD prevention measures in this population are urgent and should be primarily targeted at women and at the younger segment of this population.     

Interval cancers as related to frequency of recall to assessment in the South Australian population-based breast screening program: An exploratory study

Australian accreditation standards specify upper limits for percentages of women recalled for further assessment following screening mammography. These limits have been unchanged since national screening commenced circa 1990, although screening target ages have changed, and technology from analogue to digital mammography. This study compared 2804 women with interval cancers diagnosed since national screening began (cases) with 14,020 cancer-free controls (5 controls per case), randomly selected after matching by age, round, screen type and calendar year of screening episode, to determine the odds of interval cancer by differences in clinic recall to assessment percentages. Within low numbers of recalls that were within accepted accreditation ranges, results did not indicate more frequent recalls to assessment to be associated with fewer interval cancers in the analogue era. However, more frequent recalls were associated with reduced interval cancers for digital screens. These results are not conclusive, requiring confirmation in other screening environments, especially those with larger numbers of digital screens. If confirmed, frequency of recalls to assessment may need adjustment to get the best trade-offs in the digital era between reduced odds of interval cancers from more recalls and increases in financial and non-financial costs, including increased potential for overdiagnosis.     

Trends in advanced breast cancer incidence rates after implementation of a mammography screening program in a German population

BackgroundMammography screening programs (MSPs) aim to detect early-stage breast cancers in order to decrease the incidence of advanced-stage breast cancers and to reduce breast cancer mortality. We analyzed the time trends of advanced-stage breast cancer incidence rates in the target population before and after implementation of the MSP in a region of northwestern Germany.MethodsThe MSP in the Münster district started in October 2005. A total of 13,874 women with an incident invasive breast cancer (BC) was identified by the population-based epidemiological cancer registry between 2000 and 2013 in the target group 50–69 years. Multiple imputation methods were used to replace missing data on tumor stages (10.4%). The incidence rates for early-stage (UICC I) and advanced-stage (UICC II+) BC were determined, and Poisson regression analyses were performed to assess trends over time.ResultsThe incidence rates for UICC I breast cancers increased during the step-up introduction of the MSP and remained elevated thereafter. By contrast, after increasing from 2006 to 2008, the incidence rates of UICC II+ breast cancers decreased to levels below the pre-screening period. Significantly decreasing UICC II+ incidence rates were limited to the age group 55–69 years and reached levels that were significantly lower than incidence rates in the pre-screening period.DiscussionThe incidence rates of advanced-stage breast cancers decreased in the age groups from 55 years to the upper age limit for screening eligibility, but not in the adjacent age groups. The findings are consistent with MSP lead time effects and seem to indicate that the MSP lowers advanced-stage breast cancer rates in the target population.     

癌症中DNA甲基化基因模块筛选

肿瘤的发生受遗传学和表观遗传学修饰的共同影响。DNA甲基化是一种重要的表观遗传修饰,在癌症的发生与发展中起着重大的作用。因此找到癌症的甲基化标记物在癌症的诊断和治疗中具有重大意义。本文利用权重基因共表达网络分析的方法（WGCNA）筛选出甲基化基因模块,并分析模块向量基因,进行功能注释,最后对基因模块进行功能分析,得到DNA甲基化与肿瘤间的关系。结果显示,这些甲基化异常的基因模块与癌症的发生有着显著的关联。同时还发现某些甲基化异常的基因模块与多种癌症的发生都有着显著的关联。