Unidad Clínica de Cáncer Familiar

Miguel Urioste Jefe de Unidad Clínica
T +34 917328000 (Ext 3315)
murioste@cnio.es

Investigadores

Ana Osorio

Técnicos de Laboratorio

Alicia Barroso
Victoria Fernández
Verónica García
Fátima Mercadillo

CRC is the third most frequent type of cancer and the third cause of cancer-related deaths in most developed countries. Age is the main risk factor. The median age at diagnosis is 68 years in men and 72 in women. Since the mid-2000’s, CRC global incidence and mortality in the USA and Europe have been decreasing at an annual rate of 2-3% for both sexes. This decrease is probably related to the extended use of the faecal occult blood test and colonoscopy, which facilitates the removal of precursor lesions, and to the increased awareness among the general population of the preventive and risk factors.

Recent epidemiological studies indicate that CRC incidence in people under 50 is increasing, which is the opposite situation for individuals over 50 years of age. The greater increase was observed in the age range of 40 to 49 years, in which the incidence changed from 18.2 cases population in 1992, to a rate of 26.5 per 100,000 in 2015. This caught the attention of researchers and the general media. Several causal hypotheses were contemplated − new exogenous factors, epigenetic modifications, low-penetrance gene variants and their interactions − and there is a proposal to launch a research agenda to advance knowledge about the aetiological factors and diagnostic methods of early-onset CRC (EOCRC). Since 2010 the Familial Cancer Clinical Unit (FCCU), together with the Surgery Department of the Fundación Jiménez Díaz University Hospital and the Institute for Biomedical Research of Salamanca, has been committed to investigating EOCRC. The aim is to: (i) accelerate research to address unanswered questions about the causes of the increase in EOCRC; and (ii) increase the adoption of evidenced-based practices to identify and manage younger adults at risk for CRC and to facilitate early diagnosis.

Publicaciones

Feliubadaló L, Moles-Fernández A, Santamariña-Pena M, Sánchez AT, López-Novo A, Porras LM, Blanco A, Capellá G, de la Hoya M, Molina IJ, Osorio A, Pineda M, Rueda D, de la Cruz X, Diez O, Ruiz-Ponte C, Gutiérrez-Enríquez S, Vega A, Lázaro C (2021). A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients. Clin Chem (in press). Publicación CNIO.
Perea J, García JL, García-Olmo D, Urioste M, González-Sarmiento R; ?on behalf of the Spanish EOCRC group and the European study of EOCRC group (EUREOC) (2020). Comment On: Clinicopathological Features and Oncological Outcomes of Patients With Young-Onset Rectal Cancer. Brit J Surg 107, e277. Publicación CNIO. Open Access
Yang X et al. (incl. Osorio A) (2020). Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D. J Natl Cancer I 112, 1242-1250. Publicación CNIO.
Carreño M, Pena-Couso L, Mercadillo F, Perea J, Urioste M (2020). Investigation on the Role of PALB2 Gene in CDH1-Negative PatientsWith Hereditary Diffuse Gastric Cancer. Clin Transl Gastroenterol 11, e00280. Publicación CNIO.
Calvete O, Garcia-Pavia P, Domínguez F, Mosteiro L, Pérez-Cabornero L, Cantalapiedra D, Zorio E, Ramón Y Cajal T, Crespo-Leiro MG, Teulé Á, Lázaro C, Morente MM, Urioste M, Benitez J (2019). POT1 and Damage Response Malfunction Trigger Acquisition of Somatic Activating Mutations in the VEGF Pathway in Cardiac Angiosarcomas. J. Am. Heart Assoc. 8, e012875. Publicación CNIO. Open Access
Tapial S, Olmedillas-López S, Rueda D, Arriba M, García JL, Vivas A, Pérez J, Pena-Couso L, Olivera R, Rodríguez Y, García-Arranz M, García-Olmo D, González-Sarmiento R, Urioste M, Goel A, Perea J. (2019). Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers.. Sci Rep 9, 10516. Publicación CNIO. Open Access
Álvaro E, Cano JM, García JL, Brandáriz L, Olmedillas-López S, Arriba M, Rueda D, Rodríguez Y, Cañete Á, Arribas J, Inglada-Pérez L, Pérez J, Gómez C, García-Arranz M, García-Olmo D, Goel A, Urioste M, González-Sarmiento R, Perea J (2019). . Int J Mol Sci 20, PII:E968.. Publicación CNIO. Open Access
Arriba M, Sánchez C, Vivas A, Nutu OA, Rueda D, Tapial S, Rodríguez Y, Brandáriz L, García JL, García-Olmo D, Goel A, González-Sarmiento R, Urioste M, Perea J (2019). Intermediate-onset colorectal cancer: A clinical and familial boundary between both early and late-onset colorectal cancer. PLoS One 14, e0216472. Publicación CNIO. Open Access
Perea J, García JL, Corchete L, Lumbreras E, Arriba M, Rueda D, Tapial S, Pérez J, Vieiro V, Rodríguez Y, Brandáriz L, García-Arranz M, García-Olmo D, Goel A, Urioste M, González Sarmiento R (2019). Redefining synchronous colorectal cancers based on tumor clonality. Int J Cancer 144, 1596-1608. Publicación CNIO.
Perea García J, Arribas J, Cañete A, García JL, Álvaro E, Tapial S, Narváez C, Vivas A, Brandáriz L, Hernández-Villafranca S, Rueda D, Rodríguez Y, Pérez-García J, Olmedillas-López S, García-Olmo D, Cavestro GM, Urioste M, Goel A, González-Sarmiento R (2019). Association of polyps with early-onset colorectal cancer and throughout surveillance: novel clinical and molecular implications.. Cancers 11, pii: E1900. Publicación CNIO.
Bellido F, Sowada N, Mur P, Lázaro C, Pons T, Valdés-Mas R, Pineda M, Aiza G, Iglesias S, Soto JL, Urioste M, Caldés T, Balbín M, Blay P, Rueda D, Durán M, Valencia A, Moreno V, Brunet J, Blanco I, Navarro M, Calin GA, Borck G, Puente XS, Capellá G, Valle L (2018). Association between germline mutations in BRF1, a subunit of the RNA Polymerase III Transcription Complex, and Hereditary Colorectal Cancer. Gastroenterology 154, 181-194. Publicación CNIO.
Mur P, De Voer RM, Olivera-Salguero R, Rodríguez-Perales S, Pons T, Setién F, Aiza G, Valdés-Mas R, Bertini A, Pineda M, Vreede L, Navarro M, Iglesias S, González S, Brunet J, Valencia A, Esteller M, Lázaro C, Kops GJPL, Urioste M, Puente XS, Capellá G, Valle L (2018). Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis. Mol Can 17, 23. Publicación CNIO. Open Access
Alonso N, Cañueto J, Ciria S, Bueno E, Palacios-Alvarez I, Alegre M, Badenas C, Barreiro A, Pena L, Maldonado C, Nespeira-Jato MV, Peña-Penabad C, Azon A, Gavrilova M, Ferrer I, Sanmartin O, Robles L, Hernandez-Martin A, Urioste M, Puig S, Puig L, Gonzalez-Sarmiento R (2018). Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome. Brit J Dermatol 178, 198-206. Publicación CNIO.
Tapial S, Rueda D, Arriba M, Luis García J, Brandáriz L, Pérez J, Rodríguez Y, García-Olmo D, González-Sarmiento R, Urioste M, Perea J (2018). Comment on ‘Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system’. Br J Cancer 118, E3. Publicación CNIO.
Mur P, Jemth AS, Bevc L, Amaral N, Navarro M, Valdés-Mas R, Pons T, Aiza G, Urioste M, Valencia A, Lázaro C, Moreno V, Puente XS, Stenmark P, Warpman-Berglund U, Capellá G, Helleday T, Valle L (2018). Germline variation in the oxidative DNA repair genes NUDT1 and OGG1 is not associated with hereditary colorectal cancer or polyposis. Hum Mutat 39, 1214-1225. Publicación CNIO.
Brandariz L, Arriba M, García JL, Cano JM, Rueda D, Rubio E, Rodríguez Y, Pérez J, Vivas A, Sánchez C, Tapial S, Pena L, García-Arranz M, García-Olmo D, Urioste M, González-Sarmiento R, Perea J (2018). Differential clinicopathological and molecular features within late-onset colorectal cancer according to tumor location. Oncotarget 9, 15302-15311. Publicación CNIO. Open Access
Pena-Couso L, Perea J, Melo S, Mercadillo F, Figueiredo J, Sanches JM, Sánchez-Ruiz A, Robles L, Seruca R, Urioste M (2018). Clinical and functional characterization of the CDH1 germline variant c.1679C>G in three unrelated families with hereditary diffuse gastric cancer. Eur J Hum Genet 26, 1348-1353. Publicación CNIO.
Paumard-Hernández B, Calvete O, Inglada Pérez L, Tejero H, Al-Shahrour F, Pita G, Barroso A, Triviño JC, Urioste M, Valverde C, González Billalabeitia E, Quiroga V, Rodríguez Moreno JF, Fernández Aramburo A, López C, Maroto P, Sastre J, Juan Fita MJ, Duran I, Lorenzo-Lorenzo I, Iranzo P, García Del Muro X, Ros S, Zambrana F, Autran AM, Benítez J (2018). Whole Exome Sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer. Int J Cancer 143, 1954-1962. Publicación CNIO.
Benítez-Buelga C, Baquero JM, Vacklova T, Fernández V, Martín P, Inglada-Perez L, Urioste M, Osorio A, Benítez J (2017). Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers. Oncotarget 8, 114626-114636. Publicación CNIO. Open Access
Perea J, García JL, Pérez J, Rueda D, Arriba M, Rodríguez Y, Urioste M, González-Sarmiento R (2017). NOMO-1 gene is deleted in early-onset colorectal cancer. Oncotarget 8, 24429-24436. Publicación CNIO.
Arriba M, Sánchez R, Rueda D, Gómez L, García JL, Rodríguez Y, Díaz D, Pajares JA, Pérez J, Urioste M, González-Sarmiento R, Perea J (2017). Toward a Molecular Classification of Synchronous Colorectal Cancer: Clinical and Molecular Characterization.. Clin Colorectal Cancer 16, 31-37. Publicación CNIO.
Perea J, Arriba M, Rodríguez Y, Rueda D, García JL, Pérez J, González-Sarmiento R, Urioste M (2017). Frequency and impact of KRAS mutation in early onset colorectal cancer.. Hum Pathol 61, 221-222. Publicación CNIO.
Gayarre J, Martín-Gimeno P, Osorio A, Paumard B, Barroso A, Fernández V, de la Hoya M, Rojo A, Caldés T, Palacios J, Urioste M, Benítez J, García MJ (2017). Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.. Br J Cancer 117, 1048-1062. Publicación CNIO.
Calvete O, Garcia-Pavia P, Domínguez F, Bougeard G, Kunze K, Braeuninger A, Teule A, Lasa A, Ramón Y Cajal T, Llort G, Fernández V, Lázaro C, Urioste M, Benitez J. (2017). The wide spectrum of POT1 gene variants correlates with multiple cancer types.. Eur J Hum Genet 25, 1278-1281. Publicación CNIO.
Tavera-Tapia A, Pérez-Cabornero L, Macías JA, Ceballos MI, Roncador G, de la Hoya M, Barroso A, Felipe-Ponce V, Serrano-Blanch R, Hinojo C, Miramar-Gallart MD, Urioste M, Caldés T, Santillan-Garzón S, Benitez J, Osorio A (2017). Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.. Breast Cancer Res Treat 161, 117-134. Publicación CNIO.
Kastrinos F, Ojha RP, Leenen C, Alvero C, Mercado RC, Balmaña J, Valenzuela I, Balaguer F, Green R, Lindor NM, Thibodeau SN, Newcomb P, Win AK, Jenkins M, Buchanan DD, Bertario L, Sala P, Hampel H, Syngal S, Steyerberg EW; Lynch Syndrome prediction model validation study group (2016). Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer.. J Natl Cancer I 108, djv308. Publicación CNIO.
Perea J, Arriba M, Rueda D, Sánchez R, García JL, Pérez J, Rodríguez Y, González-Sarmiento R, Urioste M (2016). Comment on ‘Wild-type APC prediction of poor prognosis in microsatellite-stable proximal colorectal cancer differs according to the age of onset’.. Br J Cancer 114, e7. Publicación CNIO.
Mur P, Sánchez-Cuartielles E, Aussó S, Aiza G, Valdés-Mas R, Pineda M, Navarro M, Brunet J, Urioste M, Lázaro C, Moreno V, Capellá G, Puente XS, Valle L (2016). Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis. Sci Rep 6, 20697. Publicación CNIO. Open Access
Arriba M, García JL, Rueda D, Pérez J, Brandariz L, Nutu OA, Alonso L, Rodríguez Y, Urioste M, González-Sarmiento R, Perea J (2016). Unsupervised Analysis of Array Comparative Genomic Hybridization Data from Early-Onset Colorectal Cancer Reveals Equivalence with Molecular Classification and Phenotypes.. Neoplasia 19, 28-34. Publicación CNIO.
Benitez-Buelga C, Vaclová T, Ferreira S, Urioste M, Inglada-Perez L, Soberón N, Blasco MA, Osorio A, Benitez J (2016). Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers. Oncotarget 7, 25815-25825. Publicación CNIO. Open Access
Vaclová T, Woods NT, Megías D, Gomez-Lopez S, Setién F, García Bueno JM, Macías JA, Barroso A, Urioste M, Esteller M, Monteiro AN, Benítez J, Osorio A (2016). Germline missense pathogenic variants in the BRCA1 BRCT domain, p.Gly1706Glu and p.Ala1708Glu, increase cellular sensitivity to PARP inhibitor Olaparib by a dominant negative effect.. Hum Mol Genet 25, 5287-5299. Publicación CNIO.