Cantu syndrome and lymphoedema.

Three female patients with Cantu syndrome were studied, two of whom were adults presenting with the complication of lymphoedema, as described earlier in a male patient with this syndrome. The aim of this study is to report the clinical characteristics of these three new cases and to emphasize that lymphoedema, as observed in two of the patients described here, has been observed in 11.5% of patients with Cantu syndrome and that heterochromia iridis, observed in one patient, is probably a new feature of this condition.

Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population.

INTRODUCTION: Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplet repeats in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. MATERIAL AND METHODS: A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate-specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. RESULTS: The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). CONCLUSIONS: Our results suggest an association between the VDR and AR gene polymorphisms, and the histopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.

Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population / Asociación entre polimorfismo de andrógenos y receptores de vitamina D con riesgo de cáncer prostático en una población mexicana

Introduction. Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplets repetitions in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. Material and methods. A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. Results. The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). Conclusions. Our results suggest an association between the VDR and AR gene polymorphisms, and the hystopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.

Introducción. El cáncer de próstata (PCa) es un problema de salud mundial, tanto por su elevada incidencia como mortalidad. Su etiología es compleja e incluye factores de riesgo reconocidos como la edad, estado hormonal, origen étnico y antecedentes familiares de PCa. El fondo genético es un factor de riesgo y existen reportes controversiales de la asociación de PCa y polimorfismos en los genes como son los receptores de vitamina D (VDR) y el de andrógenos (AR). Objetivo. Evaluar las repeticiones de tripletes de CAG en el primer exon del AR y polimorfismos en el sitio de restricción Taql en el VDR en mexicanos con PCa. Material y métodos. Se incluyeron 68 mexicanos con diagnóstico histopatológico de PCa y 48 mexicanos con niveles normales de antígeno prostático y tacto rectal normal. Se les extrajo 10 mL de sangre periférica para aislar DNA y mediante olígos específicos se evaluaron los polimorfismos mencionados. Resultados. La distribución alélica y genotípica de los polimorfismos en el AR y VDR fueron consistentes con el equilibrio de Hardy-Weinberg, y no mostraron diferencias significativas entre los casos y controles (p > 0.05). Sin embargo, el número de repeticiones de CAG en el AR fueron estadísticamente diferentes en pacientes jóvenes con PCa comparados con los controles (p = 0.045), cuando se comparó el grupo de pacientes de jóvenes contra aquellos mayores de 60 años no se encontró diferencia estadísticamente significativa (p - 0.085); sin embargo, se observó una tendencia de un número menor de repetidos CAG en pacientes mayores con PCa. Por otra parte, al comparar VDR en los pacientes con PCa de mal pronóstico por el patrón histológico tenían menor frecuencia de genotipos TT (p - 0.03). Conclusiones. Nuestros resultados sugieren una asociación entre los polimorfismos de los genes del VDR y AR, y el patrón histológico y la edad al diagnóstico en pacientes mexicanos con PCa, respectivamente. Sin embargo, es necesario confirmar estos resultados en un estudio con mayor número de pacientes.

On the difference of micronucleus frequencies in peripheral blood lymphocytes between breast cancer patients and controls.

Sporadic breast cancer patients as well as mutation carriers of the BRCA genes have a reduced DNA repair capacity compared to controls when assessed by the G0 micronucleus test (G(0)MNT) or by induced chromosomal aberrations. Since the individual MN frequencies vary widely and overlap between cases and controls it remained unclear which percentage of the cases should be considered to exhibit an increased radiosensitivity. We performed a similar case-control study and found a highly significant difference (P < 0.0001) between all breast cancer cases (N = 91) and female controls (N = 96) using descriptive statistics and ANOVA with adjustment for age. This difference also holds for baseline MN frequencies (P = 0.0006) and for subgroups of the patients similar to those without treatment (P < 0.0001). These results were confirmed in a second sample acquired at a different hospital. Since we are dealing in this analysis with two predefined groups (patients and controls), we calculated odds ratios (ORs) in order to assess the discriminative power of the G0 MNT. These amounted to OR = 4.9 (P < 0.0001) for MN frequencies obtained by visual counting and ranged from OR = 11 (P < 0.0011) to OR = 22 (P < 0.0001) using automated counting. In order to overcome the problem of choosing a cut-off point inherent in ORs, receiver operating characteristic curves were calculated, which visualize specificity and sensitivity over the entire range of values and which characterize the discriminative power of a test by the area under the curve (AUC) (visual counting, baseline: AUC = 0.67; induced AUC = 0.75; automated counting: AUC > 0.88; evaluation sample: AUC > 0.73). We conclude that the G0 MNT may be a useful tool to substitute the phenotype breast cancer in association and linkage studies and that it may be possible to develop a test useful in the diagnosis or risk assessment for breast cancer.

Scoring variability of micronuclei in binucleated human lymphocytes in a case-control study.

The micronucleus test in binucleated lymphocytes is a sensitive standard assay for biomonitoring, mutagenicity testing and to assess radiosensitivity of blood donors. The results vary between laboratories and scorers which led to the definition of international scoring criteria. We used these criteria in a case-control study, but nevertheless observed large differences between the seven scorers on the level of descriptive analysis. Therefore, we used the repeat measurements (267 in 98 blood donors) from this dataset (354 measurements in 185 blood donors) to analyse scoring variability in the setting of a case-control study. The variability was assessed by analysis of variance, which revealed the storage time of the blood samples, the blood donors including their disease status, and the scorers as sources of variation in the entire dataset. In addition, the coefficient of variation (CV) of the measurements was determined (overall: CV = 24.3%). After stepwise removal of biological and experimental variation by normalizations, the CV dropped to 6.8% on average, which may reflect the 'pure counting error'. The scorer-specific CVs were between 5.5 and 9.5%. The differences between the scorers suggested by the raw data were neither related to the scorer-specific CV nor to their experience. Instead, we observed a general decline of the micronuclei frequencies towards the end of the study for all scorers. This could not be related to a change in experimental conditions or in the defined scoring criteria. An explanation could be an unintended and unrecognized change of scoring criteria. Since the change in the results did not occur in automated counting we suggest to use either reference slides in longer-lasting studies or automated counting by image analysis.

An automated scoring procedure for the micronucleus test by image analysis.

The micronucleus assay (MNT) in human lymphocytes is frequently used to assess chromosomal damage as a consequence of environmental mutagen exposure, to assess the effect of mutagens or to search for reduced DNA repair capacity after a mutagenic challenge. We have established an automated scoring procedure for the cytokinesis blocked MNT based on computerized image analysis (Metasystems Metafer 4 version 2.12). To evaluate the results we used the reproducibility of counts, established a dose-response curve for gamma-irradiation and used the ability of the system to differentiate between breast cancer patients and controls as a biological reference, a difference which we had observed before by visual counting. Blood cultures were irradiated with gamma-rays (2 Gy) at the beginning and treated with cytochalasin B during the last 24 h. The slides were stained with Giemsa for visual counting and with DAPI for automated analysis. Our test sample consisted of 73 persons (27 with breast cancer and 26 female and 20 male controls). A comparison between visual counting (controls, mean MN frequency 313) and automated counting (mean MN frequency 106) in slides from the same culture revealed a large drop for the automated counts. However, the automated counts were as reproducible as the visual counts [coefficient of variation (CV) on the sample approximately 20%; CV on repeated counts of the same slides approximately 5%] and both counts were highly correlated. Furthermore, the discrimination between cases and controls improved for automated counting of slides from the same cultures [visual odds rato (OR) < or = 4.0, P = 0.009; automated OR > 16, P < 0.0001], with a strong dependence on the set of parameters used. This improvement was confirmed in a validation sample of an additional 21 controls and 20 cases (OR = 11, P = 0.0018) performed as a prospective or diagnostic test.

La huella genética del DNA en Varones: haplotipo del cromosom Y en una población mexicana analizando cinco STRs / Male DNA profile: Y-chromosome haplotypes in a Mexican population analyzing five STRs

Antecedentes: Las repeticiones cortas en tándem o S TR s (short tandem repeats) localizadas en la región no seudo-autosómica del cromosoma Y , son marcadores moleculares utilizados para obtener la huella genética del DNA específicamente en varones, lo cual permite resolver casos especiales en el campo de la Medicina Legal. Analizando varios S TR s para formar haplotipos del cromosoma Y , se pueden solucionar de manera sencilla pruebas de paternidad donde el supuesto padre no está disponible, así como situaciones forenses, como casos de violación donde se encuentran mezclas de DNA de hombre y mujer. Métodos: Cinco STRs del cromosoma Y recientemente informados: A4, A7.1, A7.2, A10 y C4 (White et al. 1999) fueron tipificados en 101 mestizos mexicanos del Noroeste de México mediante PCR, electroforesis en gel de poliacrilamida y tinción de plata. Resultados: Se estimaron frecuencias alélicas de cada S TR . El rango de diversidad genética de estos marcadores fue de 57.1 por ciento para A-4 a 74.7 por ciento para C-4. Con excepción de A-4, las distribuciones alélicas de los cinco S TR s fueron similares (p>0.05) a la del reporte original. Se observaron 75 haplotipos diferentes de los 98 haplotipos completos obtenidos. Este sistema de cinco S TR s presentó una diversidad haplotípica de 99.0 por ciento y una capacidad de discriminación de 77.5 por ciento (76/98) en la muestra poblacional estudiada. Conclusiones: Estos marcadores STRs del cromosoma Y representan un gran potencial para identificar varones y líneas paternas, y pueden usarse confiablemente para lograr exclusiones en pruebas forenses y de paternidad en población mexicana.