Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

Aplicación de las plaquetas en la extrofia vesical / Use of platelet in bladder exstrophy

La extrofia vesical es una anomalía congénita grave del tracto urinario inferior que afecta la vejiga, los huesos pelvianos, la pared abdominal, los genitales externos, el perineo y, en algunos casos, el intestino. Los tratamientos convencionales están basados en técnicas quirúrgicas, para lograr reconstruir la vejiga, los genitales y cerrar el defecto de la pared. Se presenta el caso de una niña de 3 años de edad, en la que el tratamiento quirúrgico se había aplicado en 6 ocasiones sin resultados. Se decidió combinar el tratamiento quirúrgico con la aplicación de medicina regenerativa. Se le aplicó lisado de plaquetas en la pared de la vejiga y los bordes de la pared abdominal a razón de 1 mL semanal, durante 4 semanas. Se logró la regeneración de los tejidos que permitió afrontar los bordes de dichas estructuras y realizar la técnica quirúrgica convencional. Como resultado se logró cierre total de vejiga, uretra y pared abdominal, sin fístulas entre estas estructuras ni al exterior. La utilización del lisado de plaquetas favorece el crecimiento y regeneración de los tejidos que componen el tracto urinario. La cirugía puede ser una solución definitiva, después de haber aplicado los factores de crecimiento plaquetarios, que preparan el tejido en cuanto a calidad y cantidad, favoreciendo el afrontamiento de los bordes, la cicatrización y disminuyendo las complicaciones posquirúrgicas(AU)

Bladder exstrophy is a severe congenital anomaly of lower urinary tract that affects the bladder, pelvic bones, abdominal wall, external genitalia, perineum and in some cases intestine. Conventional treatments are based on surgical techniques, in order to reconstruct bladder, genitals and close wall defect. We present a case of a 3 year old girl, in which surgical treatment was applied 6 times without results. It was decided to combine the surgical treatment with application of regenerative medicine. It was applied platelet lysate in the bladder wall and the edges of the abdominal wall at the rate of 1 mL weekly for 4 weeks, achieving tissue regeneration. It enabled to face the edges of those structures and perform conventional surgical technique. As a result, we achieved a total closure of bladder, urethra and abdominal wall, without fistulas either between these structures or outside. Therefore the use of platelet lysate promotes growth and tissue regeneration comprising the urinary tract, decreasing number of interventions, time exposition structures of the abdominal cavity, and post surgical complications such as fistulas(AU)

FOXE1 Polymorphism Interacts with Dietary Iodine Intake in Differentiated Thyroid Cancer Risk in the Cuban Population.

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is low in Cuba, and the contribution of dietary factors to DTC in this population has not been investigated so far. The aim of this study was to evaluate the relationship between dietary iodine intake and DTC with regard to the interaction with environmental factors or some common single nucleotide polymorphisms (SNPs), based on a case-control study carried out in Cuba. METHODS: A total of 203 cases and 212 controls from the general population were interviewed face-to-face using the dietary intake questionnaire and the photo booklet from the E3N cohort. A specific food composition table was constructed for this study. For each parameter studied, the odds ratio (OR) was stratified on age group and sex, and further adjusted for dietary energy, smoking status, ethnic group, level of education, number of pregnancies, and body surface area. RESULTS: The risk of DTC was significantly reduced with increasing consumption of fish (p = 0.04), but no association between total dietary iodine intake and DTC risk was evident (p = 0.7). This lack of significant association was true whatever the age, the smoking status, the dietary selenium intake, and the ethnicity (p > 0.05). DTC risk was positively and strongly associated with the number of copies in the minor allele (A) for SNP rs965513 near FOXE1 among people who consumed less iodine than the median (p = 0.005). CONCLUSION: Overall, the majority of the studied population had an optimal dietary iodine intake. DTC risk was inversely associated with high fish consumption. Furthermore, DTC risk was positively associated with the number of copies in the minor allele (A) of rs965513 among people who consumed less iodine than the median. Because these findings are based on post-diagnostic measures, studies with pre-diagnostic dietary iodine are needed for confirmation.

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

PURPOSE: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk. METHODS: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status. RESULTS: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years). CONCLUSION: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.

Thyroid volume and its relation to anthropometric measures in a healthy cuban population.

OBJECTIVES: The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. STUDY DESIGN: Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. RESULTS: The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. CONCLUSION: Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit.

Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population.

BACKGROUND: The incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined. RESULTS: Significant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2-2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2-2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1-1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3-2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7-1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2-9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4-1.6) in those who had fewer than 2. CONCLUSIONS: We confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.

Environmental, lifestyle, and anthropometric risk factors for differentiated thyroid cancer in cuba: a case-control study.

BACKGROUND: The incidence of differentiated thyroid carcinoma (DTC) is low in people of African origin and higher in populations living on islands, but there is no well-established explanation for these differences. Cuba is a multiethnic nation with people of African and Spanish descent. Until now, no study on the risk factors of DTC has focused on the Cuban population. Our aim is to establish the role of environmental and lifestyle factors and to relate anthropometric measurements to the risk of developing DTC in Cuba. METHODS: We performed a case-control study of 203 DTC patients treated in two hospitals in Havana and 212 controls living in the area covered by these hospitals (i.e. parts of Havana and the municipality of Jaruco). Risk factors were analyzed using conditional logistic regression. RESULTS: As has been shown by other studies, we found that non-African ethnicity, never smoking, parity, and high body mass index are risk factors significantly associated with DTC, whereas a history of exposure to ionizing radiation and level of education were not significantly related with disease development. Being rhesus factor-positive, having a personal history of benign thyroid disorder, agricultural occupation, and consumption of artesian well water were also associated with a significantly increased risk of developing DTC. CONCLUSIONS: The original findings reported here concern the risk of DTC that was associated with non-African ethnicity, positive rhesus factor, farming, and drinking water from an artesian well.

Construction of an immunotoxin by linking a monoclonal antibody against the human epidermal growth factor receptor and a hemolytic toxin.

Hybrid molecules obtained through conjugation of monoclonal antibodies and toxins constitute an approach under exploration to generate potential agents for the treatment of cancer and other diseases. A frequently employed toxic component in the construction of such immunotoxins is ricin, a plant toxin which inhibits protein synthesis at ribosomal level and so requires to be internalized by the cell. A hemolytic toxin isolated from the sea anemone Stichodactyla helianthus, which is active at the cell membrane level, was linked through a disulfide bond to the anti-epidermal growth factor receptor monoclonal antibody ior egf/r3. The resulting immunotoxin did not exhibit hemolytic activity except under reducing conditions. It was toxic for H125 cells that express the human epidermal growth factor receptor, but non-toxic for U1906 cells that do not express this receptor.

Construction of an immunotoxin by linking a monoclonal antibody against the human epidermal growth factor receptor and a hemolytic toxin

Hybrid molecules obtained through conjugation of monoclonal antibodies and toxins constitute an approach under exploration to generate potential agents for the treatment of cancer and other diseases. A frequently employed toxic component in the construction of such immunotoxins is ricin, a plant toxin which inhibits protein synthesis at ribosomal level and so requires to be internalized by the cell. A hemolytic toxin isolated from the sea anemone Stichodactyla helianthus, which is active at the cell membrane level, was linked through a disulfide bond to the anti-epidermal growth factor receptor monoclonal antibody ior egf/r3. The resulting immunotoxin did not exhibit hemolytic activity except under reducing conditions. It was toxic for H125 cells that express the human epidermal growth factor receptor, but non-toxic for U1906 cells that do not express this receptor.

Estudio de casos y controles sobre factores de riesgo de cáncer de próstata / A case-control study on prostate cancer risks

Para determinar el papel de algunos factores genéticos, hormonales, de estilo de vida y ambientales en el riesgo de desarrollar cáncer de próstata clínicamente manifiesto en La Habana, se estudiaron los casos (n = 273) diagnosticados durante 1998-2000, con verificación histológica o citológica de cáncer de próstata, residentes en Ciudad de La Habana y menores de 85 años. Los controles (n = 254) fueron seleccionados pareados por edad, del mismo hospital del caso. La información se obtuvo mediante una entrevista. La estimación del riesgo se obtuvo a través de una regresión logística condicional. No se observó asociación estadísticamente significativa entre el color de la piel y el riesgo de cáncer de próstata (OR = 1,30, IC 95(por ciento): 0,92-1,84) ni con el hábito de fumar (OR = 0,82, IC 95(por ciento): 0,58-1,16). Se observó una asociación positiva del riesgo de cáncer de próstata con las enfermedades venéreas (p = 0,01), así como con la edad de aparición de estas enfermedades (p = 0,06). No se encontraron diferencias en cuanto a la edad de inicio de las relaciones sexuales (p = 0,111) ni en el número de compañeras sexuales (p = 0,48). Se observó una asociación significativa entre el riesgo de padecer cáncer de próstata y el haber padecido de alguna enfermedad venérea, el no realizar ejercicio físico entre los 45 y los 50 años y la frecuencia de relaciones sexuales por encima de 10 veces a la semana

Estudio de casos y controles sobre factores de riesgo de cáncer de próstata / A case-control study on prostate cancer risks

Para determinar el papel de algunos factores genéticos, hormonales, de estilo de vida y ambientales en el riesgo de desarrollar cáncer de próstata clínicamente manifiesto en La Habana, se estudiaron los casos (n = 273) diagnosticados durante 1998-2000, con verificación histológica o citológica de cáncer de próstata, residentes en Ciudad de La Habana y menores de 85 años. Los controles (n = 254) fueron seleccionados pareados por edad, del mismo hospital del caso. La información se obtuvo mediante una entrevista. La estimación del riesgo se obtuvo a través de una regresión logística condicional. No se observó asociación estadísticamente significativa entre el color de la piel y el riesgo de cáncer de próstata (OR = 1,30, IC 95(por ciento): 0,92-1,84) ni con el hábito de fumar (OR = 0,82, IC 95(por ciento): 0,58-1,16). Se observó una asociación positiva del riesgo de cáncer de próstata con las enfermedades venéreas (p = 0,01), así como con la edad de aparición de estas enfermedades (p = 0,06). No se encontraron diferencias en cuanto a la edad de inicio de las relaciones sexuales (p = 0,111) ni en el número de compañeras sexuales (p = 0,48). Se observó una asociación significativa entre el riesgo de padecer cáncer de próstata y el haber padecido de alguna enfermedad venérea, el no realizar ejercicio físico entre los 45 y los 50 años y la frecuencia de relaciones sexuales por encima de 10 veces a la semana(AU)

Sexual behaviour, history of sexually transmitted diseases, and the risk of prostate cancer: a case–control study in Cuba

Background The relationship between the risk of prostate cancer and sexual activity and history of sexually transmitted diseases was investigated in a case–control study conducted in Cuba aimed at assessing the effect of lifestyle and environmental factors, as well as hormonal and genetic factors, on the occurrence of this disease. Methods During the period 1998–2000, all men up to 84 yr old with newly diagnosed, cytologically and/or histologically confirmed prostatic cancer who were resident in Havana City were identified in nine major hospitals in the area. Controls were resident in the same city, frequency-matched by age (±5 years) and hospital. The study included 273 cases and 254 controls. Information was obtained through an interview. Results The risk of prostate cancer was increased among men with a history of venereal disease (odds ratio = 1.7, 95 percent CI = 1.1–2.5). A higher frequency of cases reported having had sex with prostitutes, although the estimate of relative risk did not reach statistical significance. Similarly, a nonsignificant positive association was found with the number of female sexual partners. A significant increased risk was observed in subjects who reported having sexual intercourse more than 7 times per week compared with those who reported a weekly frequency of 3 times or fewer (odds ratio = 2.1, 95 percent CI = 1.2–3.7). Moreover, a significant trend was demonstrated. Conclusions The study supports the hypothesis that an infectious factor related to sexual behaviour could be involved in the occurrence of prostate cancer. A role for hormonal factors related to sexual activity cannot be ruled out(AU)

Antecedentes La relación entre el riesgo de cáncer de próstata y la actividad sexual y la historia de las enfermedades de transmisión sexual se ha investigado en un estudio caso-control realizado en Cuba, destinado a evaluar el efecto de estilo de vida y factores ambientales, así como los factores genéticos y hormonales, en el aparición de esta enfermedad. Métodos Durante el período 1998-2000, todos los hombres hasta 84 años de edad, con diagnóstico reciente, citológicamente y / o histológico de cáncer de próstata que son residentes en Ciudad de La Habana fueron identificados en nueve grandes hospitales de la zona. Los controles fueron residentes en la misma ciudad, la frecuencia con ajuste por edad (± 5 años) y el hospital. El estudio incluyó 273 casos y 254 controles. La información se obtuvo a través de una entrevista. Resultados El riesgo de cáncer de próstata se incrementó entre los hombres con un historial de enfermedades venéreas (odds ratio = 1,7, IC 95 por ciento = 1.1-2.5). Una mayor frecuencia de casos notificados de haber tenido relaciones sexuales con prostitutas, aunque la estimación del riesgo relativo no alcanzó significación estadística. Del mismo modo, uno no significativo se encontró asociación positiva con el número de parejas sexuales. Un importante aumento del riesgo se observó en los sujetos que reportaron tener relaciones sexuales más de 7 veces por semana en comparación con aquellos que informaron de una frecuencia semanal de 3 veces o menos (odds-ratio = 2,1, IC 95 por ciento = 1.2-3.7). Por otra parte, una tendencia importante fue demostrado. Conclusiones El estudio apoya la hipótesis de que un factor infecciosas relacionadas con el comportamiento sexual podrían estar implicados en la aparición del cáncer de próstata. El papel de los factores hormonales relacionados con la actividad sexual no se puede descartar

Sexual behaviour, history of sexually transmitted diseases, and the risk of prostate cancer: a case-control study in Cuba.

BACKGROUND: The relationship between the risk of prostate cancer and sexual activity and history of sexually transmitted diseases was investigated in a case-control study conducted in Cuba aimed at assessing the effect of lifestyle and environmental factors, as well as hormonal and genetic factors, on the occurrence of this disease. METHODS: During the period 1998-2000, all men up to 84 yr old with newly diagnosed, cytologically and/or histologically confirmed prostatic cancer who were resident in Havana City were identified in nine major hospitals in the area. Controls were resident in the same city, frequency-matched by age (+/-5 years) and hospital. The study included 273 cases and 254 controls. Information was obtained through an interview. RESULTS: The risk of prostate cancer was increased among men with a history of venereal disease (odds ratio = 1.7, 95% CI = 1.1-2.5). A higher frequency of cases reported having had sex with prostitutes, although the estimate of relative risk did not reach statistical significance. Similarly, a nonsignificant positive association was found with the number of female sexual partners. A significant increased risk was observed in subjects who reported having sexual intercourse more than 7 times per week compared with those who reported a weekly frequency of 3 times or fewer (odds ratio = 2.1, 95% CI = 1.2-3.7). Moreover, a significant trend was demonstrated. CONCLUSIONS: The study supports the hypothesis that an infectious factor related to sexual behaviour could be involved in the occurrence of prostate cancer. A role for hormonal factors related to sexual activity cannot be ruled out.

Influencia del coralán sobre la respuesta in vitro de células inmunocompetentes / Coralan influence on the in vitro response of inmunocompetent cells

El coralán, aislado de la Pseudopterogorgia americana, un coral blando, es una glicoproteìna sulfatada que contiene 1% de sulfato, se ha informado que tienen influencia en el rechazo del trasplante del tumor ascìtico de Ehrlich. Diferentes concentraciones de esta sustancia se probaron en células mononucleares de sangre periférica (CMN) frente a la PHA, se observó un incremento significativo de la respuesta, lo que indica que una de las vías por las que este producto ajerce su actividad es por la vía de los linfocitos T. Tambièn se produce un ligero incremento de la actividad de las células NK frente a las células K 562 cuando las CMN son preincubadas con el producto 2 horas antes de realizarse el experimento, datos que en nuestras condiciones fueron comparables al procucido por el IFN, que se ha descrito que aumenta esta actividad.

Influencia del coralán sobre la respuesta in vitro de células inmunocompetentes / Coralan influence on the in vitro response of inmunocompetent cells

El coralán, aislado de la Pseudopterogorgia americana, un coral blando, es una glicoproteìna sulfatada que contiene 1

de sulfato, se ha informado que tienen influencia en el rechazo del trasplante del tumor ascìtico de Ehrlich. Diferentes concentraciones de esta sustancia se probaron en células mononucleares de sangre periférica (CMN) frente a la PHA, se observó un incremento significativo de la respuesta, lo que indica que una de las vías por las que este producto ajerce su actividad es por la vía de los linfocitos T. Tambièn se produce un ligero incremento de la actividad de las células NK frente a las células K 562 cuando las CMN son preincubadas con el producto 2 horas antes de realizarse el experimento, datos que en nuestras condiciones fueron comparables al procucido por el IFN, que se ha descrito que aumenta esta actividad.