Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence.

During the first 6 years of the Program of Genetic Counselling in Cancer of Valencia (eastern Spain), 310 mutations (155 in BRCA1 and 155 in BRCA2) in 1,763 hereditary breast (BC) and ovarian cancer (OC) families were identified. Of the mutations found 105 were distinct (53 in BRCA1 and 52 in BRCA2), eight new and 37 recurrent. Two of the novel mutations were frame-shift placed in exons 2 and 11 of BRCA1 and the remaining six were placed in BRCA2; four frame-shift (three in exon 11 and one in exon 23), one deletion of the entire exon 19 and one in the intervening sequence of exon 22. The BRCA1 mutations with higher recurrence were c.66_68delAG, c.5123C > A, c.1961delA, c.3770_3771delAG and c.5152+5G > A that covered 45.2% of mutations of this gene. The age of onset of BCs of c.68_69delAG mutation carriers occurs later than for the other recurrent mutations of this gene (45 vs. 37 years; p = 0.008). The BRCA2 mutations with higher recurrence were c.9026_9030delATCAT, c.3264insT and c.8978_8991del14 which represented 43.2% of all mutations in this gene, being the most recurrent mutation by far c.9026_9030delATCAT that represents 21.3% of BRCA2 mutations and 10.6% of all mutations. Probands with family histories of BC and OC, or OC and/or BC in at least two first degree relatives, were the more likely to have BRCA1/BRCA2 mutations (35.2% of the total mutations). And that most BRCA1mutations (73.19% mutations) occurred in probands with early-onset BC or with family history of OC.

[Programme of screening for colorrectal cancer in the Valencia community, Spain: results of the first round (2005-2008)]. / Programa de cribado de cáncer colorrectal de la comunidad valenciana: Resultados de la primera ronda: 2005-2008.

BACKGROUND: Several studies evaluating colorectal cancer (CRC) screening with fecal occult blood testing (FOBT) have reported a significant reduction in mortality from this tumor. The study aims to describe the results of the first round of the CRC screening program in medium-risk population of Valencia and assessing their feasibility and acceptability. METHODS: Colorectal cancer screening pilot study using biennial FOBT. All residents (106,000 Inhabitants) between 50 and 69 years old (a subgroup of 70-74 years), from 3 selected health departments (04, 07 and 13) were invited by mail to participate. The individuals with FOBT positive were referred to hospital for colonoscopy. The following rates were calculated as indicators of program quality: the participation rate, positive FOBT rate, acceptance rate of colonoscopy, and detection rate of low and high-risk adenomas and invasive cancers, and positive predictive value of FOBT. RESULTS: The participation was 35,231 individuals (35.70%). The number of FOBT positive was 579 (1.64% of total analyzed test), 548 people agreed colonoscopy (acceptance rate: 94.69%). 61 CRC were detected, 61 and 153 High-Risk and Low-Risk Adenomas (rates of 1.77, 1.77 and 4.46% per 1,000 participants). The positive predictive values for cancer, low-risk and high risk adenomas were 10.95%, 10.95%, and 27.46% respectively. CONCLUSION: The program indicators suggest that a population program of colorectal cancer is feasible in our community as the process indicators obtained are similar to those given in other programs in Spain and Europe.

[Evolution of meningococcal infection among infant population in the autonomous community of Valencia (1996-2000). Effectiveness of A+C meningococcal vaccination]. / Evolución de la enfermedad meningocócica en la población infantil de la Comunidad Valenciana (1996-2000). Efectividad de la vacunación antimeningocócica A + B.

BACKGROUND: The increase in meningococcal disease caused by serogroup C in the Autonomous Community of Valencia during the 1996-1997 period gave rise to an A + C meningococcal vaccination campaign having been conducted targeting the population ranging from 18 months to 19 years of age. The purpose of this study is that of analyzing the impact of this campaign regarding the epidemiology, clinical aspects and evolution of meningococcal disease and the vaccination status of the youth population for the purpose of evaluating the efficacy of this vaccination. METHODS: The data was taken from the clinical records of the children under 15 years of age who showed clinical signs and symptoms suggesting an invasive disease with isolation of Neisseria meningitidis and/or which meet the established case definition criteria which had been treated at all of the public hospital in the Autonomous Community of Valencia within the 1996-2000 period. The trend of incidence was evaluated by means of incidence rates. The clinical aspects and their progress (sequelae and lethality) by frequency and distribution by serogroup and age. The vaccination efficacy was calculated using the Orestein equation. RESULTS: A total of 302 cases of invasive disease caused by N. Meningitidis were recorded. The rate of incidence by serogroup C in children under age 15 dropped following the vaccination campaign from 5.82/10(5) habitants in 1997 to 1.68/10(5) habitants in 1998. Rates similar to those prior to the time prior to the vaccination recorded three years subsequent to the campaign, showing an increase in the disease caused by serogroup B over the last 2 years. Sixty-one percent of the sequelae were among children under 5 years of age. Lethality was higher for serogroup C. Vaccination efficacy three years subsequent to the campaign was 83.7% for the 5-14 age range and 69.1% for the 19 month-4 year age range. CONCLUSION: The polysaccharide vaccine was shown to be effective for halting the outbreak. The drop in the incidence of serogroup C can be attributed to the vaccination efficacy achieved.

Evolución de la enfermedad meningocócica en la población infantil de la Comunidad Valenciana (1996-2000). Efectividad de la vacunación antimeningocócica A+C / Evolution of Meningococcal Disease among the Infantile Population in the Autonomous Community of Valencia (1996-200). Effectivity of A+C Meningococcal Vaccination

Fundamento: El incremento de la enfermedad meningocócica por serogrupo C en la Comunidad Valenciana durante 1996-1997 motivó la realización de una campaña de vacunación antimeningocócica A+C en la población de 18 meses a 19 años de edad (entre septiembre y diciembre de 1997). El objetivo de este estudio es analizar el impacto de la campaña en cuanto a la epidemiología, clínica, evolución de la enfermedad meningocócica y estado de vacunación de la población infantil con el fin de valorar la efectividad vacunal. Métodos: Los datos se obtuvieron de las historias clínicas de los niños menores de 15 años, que presentaron síntomas y signos clínicos sugestivos de enfermedad invasora con aislamiento de Neisseria.meningitidis y/o que cumplían con los criterios de definición de caso establecidos, atendidos en todos los hospitales públicos de la Comunidad Valenciana entre 1996-2000. La evolución de la incidencia se valoró mediante tasas de incidencia. La clínica y su evolución (secuelas y letalidad) mediante la frecuencia y distribución por serogrupo y edad. La efectividad vacunal se calculó según la fórmula de Orestein. Resultados: Se registró un total de 302 casos de enfermedad invasora por N. meningitidis. La tasa de incidencia por serogrupo C en niños menores de 15 años disminuyó tras la campaña de vacunación desde 5,82/105 habitantes en 1997 a 1,68/105 habitantes en 1998. Tres años después de la campaña se ha vuelto a tasas similares a la época prevacunal, con un aumento por serogrupo B en los 2 últimos años. El 61 por ciento de las secuelas se da en menores de 5 años. La letalidad fue más elevada para el serogrupo C. La efectividad vacunal al tercer año tras la campaña ha sido del 83,7 por ciento para el grupo de 5-14 años y del 69,1 por ciento para el grupo de 19 meses-4 años. Conclusión: La vacuna polisacarídica se mostró efectiva para interrumpir el brote. La disminución de la incidencia del serogrupo C es atribuible a la efectividad vacunal obtenida (AU)

[Haemophilus Influenzae infection before and after the immunization campaign among children in the Valencia community (1996-2000)]. / Enfermedad invasora for Haemophilus Influenzae antes y después de la campaña de vacunación en la población infantil de la Comunidad Valenciana (1996-2000).

BACKGROUND: The introduction of a conjugate type b Haemophilus influenzae (Hib) vaccine for children has led to a sharp drop in the incidence of H. influenzae disease. The purpose of this study is that of analyzing the major characteristics of invasive disease due to H. influenzae as regards epidemiology, clinical aspects, evolution and immunization status among the infantile population of the Autonomous Community of Valencia for the 1996-2000 period. METHOD: The data was taken from the clinical records of those children under age 15, who have shown clinical signs and symptoms indicative of invasive disease entailing isolation of Haemophilus influenzae and/or meeting the established case definition requirements, who were treated at all of the public hospitals in the Autonomous Community of Valencia throughout the 1996-2000 period. The trend of incidence was assessed by mean of incidence rates. The clinical pattern and the evolution there of (sequelae and life-threatening aspects) by frequency and age range. RESULTS: A total of 36 cases of invasive disease due to Haemophilus influenzae were recorded. The incidence rate among children under age 15 dropped from 3.56/10(5) in 1996 to 1.07/10(5) in 1997 (coinciding with the immunization campaign and the subsequent including of the conjugate Hib vaccine in the Routine Vaccination Schedule of the Autonomous Community of Valencia) and 0.30/10(5) in 1998, this being a situation which has continued over the following years. Fifty-three percent (53%) of the cases occur in children under age 18 months. Both the sequelae as well as the deaths occurred throughout the period prior to the routine use of the conjugate vaccine. No child properly immunized died. Two cases of non-b type H. influenzae occurred in immunized children. CONCLUSIONS: The incidence of infection due to type b Haemophilus influenzae dropped drastically as of the start of the routine immunization of the infantile population.

Enfermedad invasora por Haemophilus Influenzae antes y después de la campaña de vacunación en la población infantil de la Comunidad Valenciana (1996-2000) / Invasive Disease due to Haemophilus Influenzae before and after the Immunization Campaign among the Infantile Population in the Autonomous Community of Valencia (1996-2000)

Fundamento: La introducción de la vacuna conjugada anti Haemophilus influenzae tipo b (Hib) en niños ha provocado un llamativo descenso de la incidencia de la enfermedad por H. influenzae. El objetivo de este estudio es analizar las características más relevantes de la enfermedad invasora por H. influenzae en cuanto a la epidemiología, clínica, evolución y estado de vacunación de la población infantil de la Comunidad Valenciana en el periodo 1996-2000.Método: Los datos se recogen de las historias clínicas de los niños menores de 15 años que hayan presentado síntomas y signos clínicos sugestivos de enfermedad invasora con aislamiento de Haemophilus influenzae y/o que cumple con los criterios de definición de caso establecidos, atendidos en todos los hospitales públicos de la Comunidad Valenciana entre 1996 y 2000. La evolución de la incidencia se valoró mediante tasas de incidencia. La clínica y su evolución (secuelas y letalidad) mediante la frecuencia y distribución por edad. Resultados: Se registraron un total de 36 casos de enfermedad invasora por Haemophilus influenzae. La tasa de incidencia en niños menores de 15 años pasó de 3,56/105 en 1996 a 1,07/105 en 1997 (coincidiendo con la campaña de vacunación y la posterior inclusión de la vacuna conjugada anti Hib en el Calendario de Vacunaciones Sistemáticas de la Comunidad Valenciana) y 0,30/105 en 1998, situación que se sigue manteniendo en los años posteriores. El 53 per cent de los casos se dan en menores de 18 meses. Tanto las secuelas como los fallecimientos se producen en la época anterior a la aplicación rutinaria de la vacuna conjugada. Ningún niño vacunado correctamente falleció. Se registraron 2 casos de H. influenzae tipo no b en niños vacunados. Conclusiones: La incidencia de la infección por Haemophilus influenzae tipo b disminuyó drásticamente desde el inicio de la vacunación sistemática de la población infantil. (AU)