Clinical assessment of enamel wear caused by monolithic zirconia crowns.

The purpose of this study was to measure enamel wear caused by antagonistic monolithic zirconia crowns and to compare this with enamel wear caused by contralateral natural antagonists. Twenty monolithic zirconia full molar crowns were placed in 20 patients. Patients with high activity of the masseter muscle at night (bruxism) were excluded. For analysis of wear, vinylpolysiloxane impressions were prepared after crown incorporation and at 6-, 12-, and 24-month follow-up. Wear of the occlusal contact areas of the crowns, of their natural antagonists, and of two contralateral natural antagonists (control teeth) was measured by use of plaster replicas and a 3D laser-scanning device. Differences of wear between the zirconia crown antagonists and the control teeth were investigated by means of two-sided paired Student's t-tests and linear regression analysis. After 2 years, mean vertical loss was 46 µm for enamel opposed to zirconia, 19-26 µm for contralateral control teeth and 14 µm for zirconia crowns. Maximum vertical loss was 151 µm for enamel opposed to zirconia, 75-115 µm for control teeth and 60 µm for zirconia crowns. Statistical analysis revealed significant differences between wear of enamel by zirconia-opposed teeth and by control teeth. Gender, which significantly affected wear, was identified as a possible confounder. Monolithic zirconia crowns generated more wear of opposed enamel than did natural teeth. Because of the greater wear caused by other dental ceramics, the use of monolithic zirconia crowns may be justified.

Enamel wear caused by monolithic zirconia crowns after 6 months of clinical use.

The purpose of this study was to evaluate enamel wear caused by monolithic zirconia crowns and to compare this with enamel wear caused by contralateral natural antagonists. Twenty monolithic zirconia crowns were placed in 20 patients requiring full molar crowns. For measurement of wear, impressions of both jaws were made at baseline after crown cementation and at 6-month follow-up. Mean and maximum wear of the occlusal contact areas of the crowns, of their natural antagonists and of the two contralateral natural antagonists were measured by the use of plaster replicas and 3D laser scanning methods. Wear differences were investigated by the use of two-sided paired Student's t-tests and by linear regression analysis. Mean vertical loss (maximum vertical loss in parentheses) was 10 (43) µm for the zirconia crowns, 33 (112) µm for the opposing enamel, 10 (58) µm for the contralateral teeth and 10 (46) µm for the contralateral antagonists. Both mean and maximum enamel wear were significantly different between the antagonists of the zirconia crowns and the contralateral antagonists. Gender and activity of the masseter muscle at night (bruxism) were identified as possible confounders which significantly affected wear. Under clinical conditions, monolithic zirconia crowns seem to be associated with more wear of opposed enamel than are natural teeth. With regard to wear behaviour, clinical application of monolithic zirconia crowns is justifiable because the amount of antagonistic enamel wear after 6 months is comparable with, or even lower than, that caused by other ceramic materials in previous studies.

Epigenetic screen identifies genotype-specific promoter DNA methylation and oncogenic potential of CHRNB4.

Genome-wide association studies have highlighted three major lung cancer susceptibility regions at 15q25.1, 5p15.33 and 6p21.33. To gain insight into the possible mechanistic relevance of the genes in these regions, we investigated the regulation of candidate susceptibility gene expression by epigenetic alterations in healthy and lung tumor tissues. For genes up or downregulated in lung tumors, the influence of genetic variants on DNA methylation was investigated and in vitro studies were performed. We analyzed 394 CpG units within 19 CpG islands in the susceptibility regions in a screening set of 34 patients. Significant findings were validated in an independent patient set (n=50) with available DNA and RNA. The most consistent overall DNA methylation difference between tumor and adjacent normal tissue on 15q25 was tumor hypomethylation in the promoter region of CHRNB4 with a median difference of 8% (P<0.001), which resulted in overexpression of the transcript in tumors (P<0.001). Confirming previous studies, we also found hypermethylation in CHRNA3 and telomerase reverse transcriptase (TERT) with significant expression changes. Decitabine treatment of H1299 cells resulted in reduced methylation levels in gene promoters, elevated transcript levels of CHRNB4 and CHRNA3, and a slight downregulation of TERT demonstrating epigenetic regulation of lung cancer cells. Single-nucleotide polymorphisms rs421629 on 5p15.33 and rs1948, rs660652, rs8040868 and rs2036527 on 15q25.1, previously identified as lung cancer risk or nicotine-addiction modifiers, were associated with tumor DNA methylation levels in the promoters of TERT and CHRNB4 (P<0.001), respectively, in two independent sample sets (n=82; n=150). In addition, CHRNB4 knockdown in two different cell lines (A549 and H1299) resulted in reduced proliferation (PA549<0.05;PH1299<0.001) and propensity to form colonies in H1299 cells. These results suggest epigenetic deregulation of nicotinic acetylcholine receptor subunit (nAChR) genes which in the case of CHRNB4 is strongly associated with genetic lung cancer susceptibility variants and a functional impact on tumorigenic potential.

Significance of the intraoperative methylene blue test for postoperative evaluation of the vesicourethral anastomosis.

We prospectively investigated whether routine evaluation of the vesicourethral anastomosis (VUA) after radical prostatectomy can be waived. Primary integrity of the VUA was analysed by an intraoperative methylene-blue test (IMBT) and postoperatively by conventional cystography. Data on the IMBT, contrast extravasation and prostate volume as well as pad usage were collected prospectively. Significantly more patients with a primary watertight anastomosis demonstrated by the MBT had no leakage in the postoperative cystography (P < 0.001). In a multivariate logistic regression with adjustment for prostate size and surgeon, the positive correlation between IMBT and postoperative cystography remained statistically significant (P = 0.001). The IMBT is easy to perform, inexpensive, and timesaving. With it postoperative evaluation of VUA for integrity can be waived in a significant number of patients. Following our algorithm, the Foley can be removed without further testing of the VUA, whenever the IMBT detected no leakage.

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma.

Aberrant promoter methylation of different DNA repair genes has a critical role in the development and progression of various cancer types, including head and neck squamous cell carcinomas (HNSCCs). A systematic analysis of known human repair genes for promoter methylation is however missing. We generated quantitative promoter methylation profiles in single CpG units of 160 human DNA repair genes in a set of DNAs isolated from fresh frozen HNSCC and normal tissues using MassARRAY technology. Ninety-eight percent of these genes contained CpG islands (CGIs) in their promoter region; thus, DNA methylation is a potential regulatory mechanism. Methylation data were obtained for 145 genes, from which 15 genes exhibited more than a 20% difference in methylation levels between tumor and normal tissues, manifested either as hypermethylation or as hypomethylation. Analyses of promoter methylation with mRNA expression identified the DNA glycosylase NEIL1 (nei endonuclease VIII-like 1) as the most prominent candidate gene. NEIL1 promoter hypermethylation was confirmed in additional fresh frozen HNSCC samples, normal mucosa, HNSCC cell lines and primary human skin keratinocytes. The investigation of laser-microdissected tissues further substantiated increased methylation levels in tumor versus matched non-tumor cells. Immunohistological analysis revealed significantly less NEIL1 protein expression in tumor tissues. 5-Aza-2'-deoxycytidine treatment and DNMT1 knockdown resulted in the re-expression of NEIL1 in HNSCC cell lines, which initially carried hypermethylated promoter regions. In conclusion, our results suggest that DNA methylation contributes to the downregulation of NEIL1 expression and might thus have a role in modulating the response to therapies of HNSCC.

Prostate cancer as a first and second cancer: effect of family history.

BACKGROUND: Diagnosis with prostate cancer has been reported to increase the risk of subsequent tumours. However, specific data on individuals with a parental history are not available so far. METHODS: On the basis of the nationwide Swedish Family-Cancer Database including 18,207 primary invasive prostate cancers, standardised incidence ratios (SIRs) were used to estimate the relative risks of subsequent tumours after prostate cancer in the general population and among individuals with a parental history of cancer. RESULTS: A significantly increased SIR of colorectal cancer was found among prostate cancer patients with a parental history of colorectal cancer (2.26, 11 cases). The SIRs of parental concordant (same site) tumours after prostate cancer were also increased for urinary bladder cancer (4.42, 4 cases) and chronic lymphoid leukaemia (38.0, 2 cases). CONCLUSION: A higher than additive and multiplicative interaction was observed between the individual history of prostate cancer and parental history of colorectal and urinary bladder cancers, although the number of cases did not permit the rejection of any interaction model. The results suggest that the occurrence of second tumours, for example bladder after prostate or prostate after bladder tumours, is mostly related to shared genetic and non-genetic risk factors rather than treatment of first cancer.

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic.

The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population.

How common is familial cancer?

BACKGROUND: Family history of a disease may point to its heritable or environmental etiology. It can be described by the proportion of the familial disease, i.e. same disease in two or more family members. A family history always needs to be specified as to the number of generations covered and their ages. PATIENTS AND METHODS: Proportions of site-specific familial cancers (familial proportions) were calculated using the Swedish Family-Cancer Database, the largest dataset of its kind in the world, with cancers from the Swedish Cancer Registry. Familial proportions refer to the offspring population up to age 72 years when their parents or siblings were diagnosed with a concordant (same) cancer. RESULTS: A total of 34 cancer sites and 205 638 cases were covered. Prostate cancer showed the highest familial proportion of 20.15%, followed by breast (13.58%) and colorectal (12.80%) cancers. Salivary gland cancers showed the lowest familial proportion of 0.15%, but bone, laryngeal, anal, connective tissue and other genital cancers also remained <1%. The familial proportion depended on the prevalence of the particular cancer and on its familial risk. CONCLUSIONS: The derived familial proportions can justifiably be used in statements 'X% of the patients had a family history of the cancer'.

Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: a case-control study.

We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk.