TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. FUNDING: German Research Foundation (DFG).

[The prevalence of tetracycline resistance genes in clinical and commensal strains of Enterococcus faecalis isolated in Gdansk]. / Wystepowanie i zróznicowanie genów odpowiedzialnych za opornosc na tetracykline szczepów Enterococcus faecalis izolowanych w regionie gdanskim.

The common use of antibiotics is responsible for selecting of drug resistance not only in pathogenic, clinical bacteria but also in commensal, not pathogenic strains which could cause the rapid dissemination of the resistance to these antibacterial agents. However, information regarding the antibiotic resistance of commensal bacteria is very scarce, and the data is based mostly on phenotypical research. Therefore the use of genotyping methods for detection of tetracycline resistance genes, in commensal and medical isolates of bacteria, is essential, for understanding the spread of antibiotic resistance. In this study 24 commensal and 27 clinical isolates of Enterococcus faecalis has been screened by PCR methods for tet(M), tet(S) genes and Tn916 and Tn5397 transpozons. Subsequently, the tet(M) gene amplicones were sequenced and phylogenetic analysis was performed. We have found that the prevalence of tet(S) gene varied significantly between commensal and clinical strains. Moreover, the frequency of transpozons in clinical isolates was much higher comparing to strains isolated from healthy individuals. The phylogenetic analysis did not show significant differences between clinical and commensal strains but it could suggest that the genetic similarity between these two groups could be favourable factor for broad range spread of tet(M) gene.

Genetic variability of hepatitis B virus isolates in Poland.

There is very limited knowledge about the genetic variability of HBV strains circulating in the population of Polish chronically infected HBV patients. The aim of this study was to analyse the phylogenetic relatedness and polymorphism in some functional domains of HBV genome among chronically infected patients from northern Poland. Fifty-one serum samples were included to analysis of HBV genomes due to the viral load sufficient for DNA preparation and sequencing. The sequences of the rt polymerase/S and preC/BCP regions of those isolates were analysed, compared to genome sequences of different variants of HBV from GenBank database and genetic relatedness of Polish genotypes to known reference strains was estimated. A phylogenetic tree of 41 analysed genotype A isolates as well as 8 genotype D strains was constructed showing relationship to know reference strains. Two isolates, initially classified as genotype F turned to be related to genotype H, newly described genotype deriving from genotype F, a very rare genotype in Europe. HBV genotypes' distribution pattern in Poland and phylogenetic relatedness seems to be different from our Eastern neighbours. Due to the fact that Poland is still ethnically uniform country, it is interesting to explore molecular epidemiology of HBV infections in our population.

Evaluation of Fas gene promoter polymorphism in cervical cancer patients.

Transduction of signalling through Fas receptor has been implicated in physiological regulation of apoptosis process as well as pathogenesis of various human diseases. The gene encoding Fas receptor contains single nucleotide polymorphism at -670 position, which influences the expression by different transcriptional efficiency of this gene. The aim of this study was to determine the distribution of -670 A/G Fas gene promoter polymorphism in cervical cancer patients and healthy control group in Poland in order to evaluate the potential association between Fas genotype and cervical carcinogenesis. Our results do not confirm the hypothesis that AA genotype in Fas gene promoter may be engaged in the development of cervical neoplasia.

Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland.

Hepatitis B virus (HBV) infection is one of the major global epidemiological problems. The aim of our study was to determine the distribution of HBV genotypes in Poland since the data concerning the spread of HBV viruses in the central-eastern region of Europe is still very limited. HBV DNA was extracted from 58 serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were performed. The HBV virus from 43 serum samples from hepatitis B infected patients was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most prevalent subtype in the Amerindians. Our results coincide with the general European HBV prevalence. However, HBV genotype F, which is not a common genotype in European countries, was detected and so was relatively high occurrence of genotype D, which may reflect historical and ethnical migration events in Poland in the past.

HPV detection in cervical cancer patients in northern Poland.

Human papillomaviruses (HPVs) are associated with various benign and malignant lesions including genital condyloma and anogenital cancer. Epidemiological data show that about 90% of all cervical cancer patients are HPV positive. The aim of our study was to determine the percentage of HPV infections in Polish population of examined women. To detect viral DNA, PCR method was used. To distinguish between different virus types, RFLP analysis was performed. Results obtained by PCR-RFLP method were verified by Hybrid Capture test. The presence of HPV DNA was detected in 53% of cervical cancer patients and in 2% of control group of healthy women. The agreement for HPV detection between PCR and Hybrid Capture methods was 81%. Our studies showed much lower incidence of HPV in Polish women with cervical cancer than among other populations as reported in world literature. HPV detection as well as determination of other factors involved in pathogenesis of cervical cancer is of great importance.