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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. Radium Hospital Foundation (Oslo, Norway)

RESUMEN Este articulo analiza el rol de las imagenes en diferentes sindromes neoplasicos hereditarios, incluyendo mama, colon y neoplasias endocrinas multiples. Las mujeres con mutaciones geneticas asociadas a mayor susceptibilidad de desarrollar cancer de mama pueden optar a la vigilancia con imagenes desde edades tempranas, detectando asi precozmente la enfermedad. En este grupo de mujeres, la mamografia ha mostrado un bajo rendimiento, mientras que la resonancia mamaria se ha establecido como el principal metodo de screening. El cancer colorrectal es una patologia muy frecuente en nuestra poblacion. Un 2-5% constituyen sindromes hereditarios, de los cuales el mas frecuente es el Sindrome de Lynch o cancer colorrectal hereditario no poliposico, seguido de la Poliposis Adenomatosa Familiar y otras poliposis. La importancia de detectar estos sindromes esta en identificar los individuos en riesgo, y realizar metodos de tamizaje apropiados para una deteccion precoz del cancer. Las Neoplasias Endocrinas Multiples incluyen entre sus manifestaciones los tumores paratiroideos, los feocromocitomas, los tumores gastroenteropancreaticos y el cancer medular de tiroides. Estas lesiones presentan caracteristicas fisiologicas como expresion de receptores o hiperfuncion celular que permiten obtener imagenes con tecnicas de Medicina Nuclear que actualmente se denominan Imagenes Moleculares.

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5–10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant, 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels.

Una proporción de los cánceres colorrectales presentan algún tipo de predisposición genética que es posible reconocer en la práctica clínica. Desde los clásicos patrones hereditarios dominantes de la poliposis adenomatosa familiar o el cáncer de colon hereditario no asociado a poliposis, pasando por la transmisión recesiva mostrada por la poliposis asociada al gen MYH, hasta llegar a los novedosos síndromes de la "vía serrada" o los alelos de baja penetrancia, el descubrimiento de nuevos genes y el mejor conocimiento de los mecanismos de acción de los ya conocidos, están permitiendo comprender nuevos aspectos de la carcinogénesis colorrectal que arrojan nueva luz sobre algunas de las observaciones de patrones de agregación familiar al cáncer de colon que permanecían inexplicadas.

Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer. In contrast to the classic dominant condition of familial adenomatous polyposis (FAP) due to germinal mutations in the APC gene, the MYH polyposis is an autosomal recessive disease. The identification of individuals affected by MYH polyposis brings new and important implications for the diagnostic, screening, genetic counseling, follow up and therapeutic options in these patients. In this study, screening for germinal mutations in the MYH gene was performed in 53 Portuguese individuals with multiple colorectal adenomas or classic adenomatous polyposis, in whom no mutation had been identified in the APC gene. The results revealed the presence of biallelic germline MYH mutations in 21 patients. In addition, we here report 3 mutations (c.340T>C [p.Y114H]; c.503G>A [p.R168H]; and c.1186_1187insGG [p.E396fsX437]) which, to our knowledge, have not been previously described. © 2004 Wiley-Liss, Inc.