24 research outputs found

    Aspectos genético-moleculares asociados con el desarrollo del carcinoma colorrectal

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    El presente trabajo es el resultado de la revisiĂłn bibliogrĂĄfica en PubMed y ScienceDirect, de 62 artĂ­culos, relacionados con aspectos genĂ©tico-moleculares del carcinoma colorrectal (CCR). El CCR constituye un problema de salud pĂșblica, agravado en los paĂ­ses en desarrollo, porque la mayorĂ­a de los casos se diagnostican en estados avanzados, al punto que, en Colombia, los datos de mortalidad se asemejan a los de incidencia, lo cual no es comĂșn en los paĂ­ses desarrollados. En consecuencia, es importante implementar mĂ©todos de detecciĂłn temprana, tratamientos efectivos y procedimientos genĂ©tico-moleculares, para diferenciar los casos y ofrecer tratamientos de acuerdo con el perfil genĂ©tico del paciente.  Se hace referencia a las pruebas moleculares de inestabilidad microsatelital e inmunohistoquimica para proteĂ­nas del grupo mismatch repear (MMR),  que por su alta sensibilidad y especificidad resultan indispensables para la clasificaciĂłn y tamizaje del CCR y la discriminaciĂłn del mismo, entre esporĂĄdico y hereditario

    From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

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    Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.Fil: Vaccaro, Carlos Alberto. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: LĂłpez Kostner, Francisco. No especifĂ­ca;Fil: Adriana, Della Valle. Hospital Fuerzas Armadas; UruguayFil: Inez Palmero, Edenir. Hospital de cĂĄncer de Barretos, FACISB; BrasilFil: Rossi, Benedito Mauro. Hospital Sirio Libanes; BrasilFil: Antelo, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital de GastroenterologĂ­a "Dr. Carlos B. Udaondo"; Argentina. Universidad Nacional de LanĂșs; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Solano, Angela Rosario. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas; ArgentinaFil: Carraro, Dirce Maria. No especifĂ­ca;Fil: Forones, Nora Manoukian. Universidade Federal de Sao Paulo; BrasilFil: Bohorquez, Mabel. Universidad del Tolima; ColombiaFil: Lino Silva, Leonardo S.. Instituto Nacional de Cancerologia; MĂ©xicoFil: Buleje, Jose. Universidad de San MartĂ­n de Porres; PerĂșFil: Spirandelli, Florencia. No especifĂ­ca;Fil: Abe Sandes, Kiyoko. Universidade Federal da Bahia; BrasilFil: Nascimento, Ivana. No especifĂ­ca;Fil: Sullcahuaman, Yasser. Universidad Peruana de Ciencias Aplicadas; PerĂș. Instituto de InvestigaciĂłn Genomica; PerĂșFil: Sarroca, Carlos. Hospital Fuerzas Armadas; UruguayFil: Gonzalez, Maria Laura. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica - Hospital Italiano. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica; ArgentinaFil: Herrando, Alberto Ignacio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica - Hospital Italiano. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica; ArgentinaFil: Alvarez, Karin. No especifĂ­ca;Fil: Neffa, Florencia. Hospital Fuerzas Armadas; UruguayFil: GalvĂŁo, Henrique Camposreis. Barretos Cancer Hospital; BrasilFil: Esperon, Patricia. Hospital Fuerzas Armadas; UruguayFil: Golubicki, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de GastroenterologĂ­a "Dr. Carlos B. Udaondo"; ArgentinaFil: Cisterna, Daniel. Gobierno de la Ciudad de Buenos Aires. Hospital de GastroenterologĂ­a "Dr. Carlos B. Udaondo"; ArgentinaFil: Cardoso, Florencia C.. Centro de EducaciĂłn Medica E Invest.clinicas; ArgentinaFil: Tardin Torrezan, Giovana. No especifĂ­ca;Fil: Aguiar Junior, Samuel. No especifĂ­ca;Fil: Aparecida Marques Pimenta, CĂ©lia. Universidade Federal de Sao Paulo; BrasilFil: Nirvana da Cruz Formiga, MarĂ­a. No especifĂ­ca;Fil: Santos, Erika. Hospital Sirio Libanes; BrasilFil: SĂĄ, Caroline U.. Hospital Sirio Libanes; BrasilFil: Oliveira, Edite P.. Hospital Sirio Libanes; BrasilFil: Fujita, Ricardo. Universidad de San MartĂ­n de Porres; PerĂșFil: Spirandelli, Enrique. No especifĂ­ca;Fil: Jimenez, Geiner. No especifĂ­ca;Fil: Santa Cruz Guindalini, Rodrigo. Universidade de Sao Paulo; BrasilFil: Gondim Meira Velame de Azevedo, Renata. No especifĂ­ca;Fil: Souza Mario Bueno, Larissa. Universidade Federal da Bahia; BrasilFil: dos Santos Nogueira, Sonia Tereza. No especifĂ­ca;Fil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica - Hospital Italiano. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e IngenierĂ­a BiomĂ©dica; Argentin

    Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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    Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

    Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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    Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.publishedVersionPeer reviewe

    The HABP2 G534E variant is an unlikely cause of familial non-medullary thyroid cancer

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    ContextA recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC).ObjectiveThe objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles.Design and settingA case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls.ParticipantsCases comprised 2,105 NMTC cases. Patients sub-groups with papillary (N=1,056), follicular (N=691) and Hurthle cell (N=86) TC cases were studied separately. Controls comprised 5,172 individuals from the 1958 Birth Cohort (58C) and the National Blood Donor Service (NBS) study. The controls had previously been genotyped using genome-wide SNP arrays by the Wellcome Trust Case Control Consortium study.OutcomeMeasures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression.ResultsThe frequency of HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (OR=0.896, 95% CI: 0.746-1.071, P=0.233). We also failed to detect an association between HABP2 G534E and cases with papillary (1056 cases, G534E frequency= 3.5%, OR=0.74, P=0.017), follicular (691 cases, G534E frequency= 4.7%, OR=1.00, P=1.000) or Hurthle cell (86 cases, G534E frequency= 6.3%, OR=1.40, P=0.279) histology.ConclusionsWe found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC and additional data are required before using this variant in NMTC risk assessment

    Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

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    Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer
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