2023
Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico
Perez-Mayoral J, Gonzalez-Pons M, Centeno-Girona H, Montes-Rodríguez I, Soto-Salgado M, Suárez B, Rodríguez N, Colón G, Sevilla J, Jorge D, Llor X, Xicola R, Toro D, Tous-López L, Torres-Torres M, Reyes J, López-Acevedo N, Goel A, Rodríguez-Quilichini S, Cruz-Correa M. Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico. Genes 2023, 14: 894. PMID: 37107652, PMCID: PMC10138302, DOI: 10.3390/genes14040894.Peer-Reviewed Original ResearchConceptsEarly-onset colorectal cancerColorectal cancerCpG island methylator phenotypeMicrosatellite instabilityExact testColorectal cancer disparitiesSporadic colorectal cancerFisher's exact testMolecular carcinogenic pathwaysClinicopathologic featuresClinicopathological characteristicsCancer deathCancer disparitiesColorectal tumorsCarcinogenic pathwaysHispanic menMutation statusTumorsAdditional studiesMethylator phenotypeHispanic subpopulationsChi-squaredAmerindian admixtureMolecular pathwaysMolecular markers
2022
Simplified and more sensitive criteria for identifying individuals with pathogenic CDH1 variants
Lerner BA, Xicola RM, Rodriguez NJ, Karam R, Llor X. Simplified and more sensitive criteria for identifying individuals with pathogenic CDH1 variants. Journal Of Medical Genetics 2022, 60: 36-40. PMID: 35078942, PMCID: PMC9661780, DOI: 10.1136/jmedgenet-2021-108169.Peer-Reviewed Original ResearchConceptsInternational Gastric Cancer Linkage ConsortiumHereditary diffuse gastric cancerPercentage of subjectsGastric cancerMutation carriersPathogenic variantsMultigene panel testingPathogenic CDH1 variantsAutosomal dominant syndromeDiffuse gastric cancerClinical criteriaConsecutive casesMedical historyPathology reportsCDH1 variantsPanel testingGenetic testingCancer pathology reportsCancerPathology
2021
Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers
Grant A, Xicola RM, Nguyen V, Lim J, Thorne C, Salhia B, Llor X, Ellis N, Padi M. Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers. Scientific Reports 2021, 11: 23507. PMID: 34873211, PMCID: PMC8648784, DOI: 10.1038/s41598-021-02806-x.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis ColiAdenomatous Polyposis Coli ProteinColorectal NeoplasmsDisease ProgressionDNA Copy Number VariationsDNA MethylationGenes, APCHumansMicrosatellite InstabilityMicrosatellite RepeatsMutationNeoplastic ProcessesPhenotypePromoter Regions, GeneticWnt Signaling PathwayConceptsAdenomatous polyposis coliMitochondrial activationDNA methylation profilesTumor suppressor gene adenomatous polyposis coliRNA expressionExpression of Axin2Cancer Genome AtlasIntracellular WntMethylation profilesAberrant regulationGene fusionsGenetic inactivationExtracellular WntNumber variationsGenome AtlasPolyposis coliSomatic mutationsAPC mutationsMutationsMolecular driversMutations of BRAFWntRSPO3Tumor progressionExpressionColorectal Cancer Risk in Lynch Syndrome: Of Genes and More
Mezzacappa C, Llor X. Colorectal Cancer Risk in Lynch Syndrome: Of Genes and More. Gastroenterology 2021, 162: 1358-1360. PMID: 34863785, DOI: 10.1053/j.gastro.2021.11.032.Peer-Reviewed Original ResearchxDEEP-MSI: Explainable Bias-Rejecting Microsatellite Instability Deep Learning System in Colorectal Cancer
Bustos A, Payá A, Torrubia A, Jover R, Llor X, Bessa X, Castells A, Carracedo Á, Alenda C. xDEEP-MSI: Explainable Bias-Rejecting Microsatellite Instability Deep Learning System in Colorectal Cancer. Biomolecules 2021, 11: 1786. PMID: 34944430, PMCID: PMC8699085, DOI: 10.3390/biom11121786.Peer-Reviewed Original ResearchNCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.
Weiss JM, Gupta S, Burke CA, Axell L, Chen LM, Chung DC, Clayback KM, Dallas S, Felder S, Gbolahan O, Giardiello FM, Grady W, Hall MJ, Hampel H, Hodan R, Idos G, Kanth P, Katona B, Lamps L, Llor X, Lynch PM, Markowitz AJ, Pirzadeh-Miller S, Samadder NJ, Shibata D, Swanson BJ, Szymaniak BM, Wiesner GL, Wolf A, Yurgelun MB, Zakhour M, Darlow SD, Dwyer MA, Campbell M. NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021. Journal Of The National Comprehensive Cancer Network 2021, 19: 1122-1132. PMID: 34666312, DOI: 10.1164/jnccn.2021.0048.Peer-Reviewed Original ResearchConceptsGenetic/Familial High-Risk AssessmentFamilial adenomatous polyposisHigh-risk assessmentNCCN guidelinesHereditary cancer risk assessmentNCCN Guidelines InsightsManagement of patientsColorectal cancer syndromeFamilial adenomatous polyposis syndromeAdenomatous polyposis syndromeCancer risk assessmentPathogenic genetic variantsDuodenal neoplasiaCancer surveillancePolyposis syndromeHereditary syndromesIdentification of individualsCancer syndromesAdenomatous polyposisClinical expertiseSyndromeColorectalRisk reductionGenetic variantsNew scientific dataAnalysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database
Cheng E, Blackburn HN, Ng K, Spiegelman D, Irwin ML, Ma X, Gross CP, Tabung FK, Giovannucci EL, Kunz PL, Llor X, Billingsley K, Meyerhardt JA, Ahuja N, Fuchs CS. Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database. JAMA Network Open 2021, 4: e2112539. PMID: 34132794, PMCID: PMC8209612, DOI: 10.1001/jamanetworkopen.2021.12539.Peer-Reviewed Original ResearchConceptsEarly-onset colorectal cancerOnset colorectal cancerNational Cancer DatabaseColorectal cancerAge 51Overall survivalCancer DatabaseIncidence of CRCCox proportional hazards regressionPrimary colorectal cancerKaplan-Meier analysisProportional hazards regressionAge 50 yearsAge 25 yearsAnalysis of survivalCohort studySurvival benefitHazards regressionUnadjusted analysesCancer incidenceMAIN OUTCOMEAge 35Survival advantageLower riskStage IExome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer
Fernández-Rozadilla C, Álvarez-Barona M, Quintana I, López-Novo A, Amigo J, Cameselle-Teijeiro J, Roman E, Gonzalez D, Llor X, Bujanda L, Bessa X, Jover R, Balaguer F, Castells A, Castellví-Bel S, Capellá G, Carracedo A, Valle L, Ruiz-Ponte C. Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer. Scientific Reports 2021, 11: 11135. PMID: 34045552, PMCID: PMC8159954, DOI: 10.1038/s41598-021-90590-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultColorectal NeoplasmsDNA HelicasesDNA Repair EnzymesDNA-Binding ProteinsExomeExome SequencingFemaleGene Expression Regulation, NeoplasticGenetic HeterogeneityGenetic Predisposition to DiseaseHumansMaleMethyltransferasesMiddle AgedPoly-ADP-Ribose Binding ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 13ConceptsEarly-onset CRC patientsColorectal cancerCRC patientsEarly-onset patientsGenetic variantsPotential risk allelesCRC onsetYoungest caseCRC developmentIndependent patientsPatientsTruncating variantsRisk allelesExome sequencingNovel genetic variantsRobust studiesTDG geneDisease developmentCandidate variantsCancerMolecular heterogeneityDiseaseComplex diseasesGenetic heterogeneityHigh-impact variantsPhenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant
MacFarland SP, Ebrahimzadeh JE, Zelley K, Begum L, Bass LM, Brand RE, Dudley B, Fishman DS, Ganzak A, Karloski E, Latham A, Llor X, Plon S, Riordan MK, Scollon SR, Stadler ZK, Syngal S, Ukaegbu C, Weiss JM, Yurgelun MB, Brodeur GM, Mamula P, Katona BW. Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant. Cancer Prevention Research 2021, 14: 215-222. PMID: 33097490, PMCID: PMC8557953, DOI: 10.1158/1940-6207.capr-20-0348.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedBone Morphogenetic Protein Receptors, Type IChildChild, PreschoolColectomyColonoscopyFemaleFollow-Up StudiesGerm-Line MutationHumansIntestinal PolyposisMaleMedical History TakingMiddle AgedNeoplastic Syndromes, HereditaryPractice Guidelines as TopicPrecision MedicineSmad4 ProteinWatchful WaitingYoung AdultConceptsJuvenile polyposis syndromePolyposis syndromeFamily historyDisease-causing variantsCancer riskGermline disease-causing variantsGastrointestinal cancer predisposition syndromesUpper gastrointestinal polypsHamartomatous polyposis syndromesCancer predisposition syndromeLifelong surveillanceAdult centersDuodenal polypsGastrointestinal cancerCancer historySubgroup analysisIndividualized managementLower riskGastrointestinal polypsPredisposition syndromeSyndromeYounger ageDistinct phenotypic differencesLower likelihoodGastrectomy
2020
NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020.
Provenzale D, Ness RM, Llor X, Weiss JM, Abbadessa B, Cooper G, Early DS, Friedman M, Giardiello FM, Glaser K, Gurudu S, Halverson AL, Issaka R, Jain R, Kanth P, Kidambi T, Lazenby AJ, Maguire L, Markowitz AJ, May FP, Mayer RJ, Mehta S, Patel S, Peter S, Stanich P, Terdiman J, Keller J, Dwyer MA, Ogba N. NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020. Journal Of The National Comprehensive Cancer Network 2020, 18: 1312-1320. PMID: 33022639, PMCID: PMC8311627, DOI: 10.6004/jnccn.2020.0048.Peer-Reviewed Original ResearchConceptsColorectal cancer screeningNCCN guidelinesCancer screeningAverage-risk individualsNCCN Guidelines InsightsLow-risk adenomasCRC preventionSporadic CRCScreening scheduleRisk individualsGenetic syndromesPanel recommendationsPatientsRecent updatesCRCScreeningGuidelinesAdenomasSyndromePhysiciansPreventionAGA White Paper: Roadmap for the Future of Colorectal Cancer Screening in the United States
Melson JE, Imperiale TF, Itzkowitz SH, Llor X, Kochman ML, Grady WM, Schoen RE, Burke CA, Shaukat A, Rabeneck L, Ladabaum U, Bresalier R, Spiegel B, Yee J, Wang T, Lieberman D, Komanduri S, Muthusamy VR, Dey N. AGA White Paper: Roadmap for the Future of Colorectal Cancer Screening in the United States. Clinical Gastroenterology And Hepatology 2020, 18: 2667-2678.e2. PMID: 32634626, DOI: 10.1016/j.cgh.2020.06.053.Peer-Reviewed Original ResearchConceptsColorectal cancer screeningCancer screeningBetter risk-stratify patientsMultiple screening modalitiesRisk-stratify patientsNoninvasive screening testAmerican Gastroenterological Association's CenterPersonal risk assessmentCRC morbidityCRC screeningCRC outcomesScreening modalityConsensus conferenceScreening testAssociation centerOutcomesScreeningTesting paradigmSurveillanceMorbidityPatientsRisk assessmentMortalityUptakeDecreased copy‐neutral loss of heterozygosity in African American colorectal cancers
Augustus GJ, Xicola RM, Llor X, Ellis NA. Decreased copy‐neutral loss of heterozygosity in African American colorectal cancers. Genes Chromosomes And Cancer 2020, 59: 454-464. PMID: 32293075, PMCID: PMC8045478, DOI: 10.1002/gcc.22851.Peer-Reviewed Original Research
2019
Scoring colorectal cancer risk with an artificial neural network based on self-reportable personal health data
Nartowt BJ, Hart GR, Roffman DA, Llor X, Ali I, Muhammad W, Liang Y, Deng J. Scoring colorectal cancer risk with an artificial neural network based on self-reportable personal health data. PLOS ONE 2019, 14: e0221421. PMID: 31437221, PMCID: PMC6705772, DOI: 10.1371/journal.pone.0221421.Peer-Reviewed Original ResearchConceptsNational Health Interview SurveyUnited States Preventative Services Task ForceColorectal cancerPredictive valueDiagnosis of CRCColorectal cancer riskHealth Interview SurveyHigh-risk categoryNegative predictive valuePositive predictive valueMultivariable prediction modelHealth dataUSPSTF guidelinesRisk score methodCRC riskFamily historyCancer riskHigh riskAge 50Individual prognosisLower riskPersonal health dataClinical applicabilityInterview SurveyCancerClinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria
Xicola RM, Li S, Rodriguez N, Reinecke P, Karam R, Speare V, Black MH, LaDuca H, Llor X. Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria. Journal Of Medical Genetics 2019, 56: 838. PMID: 31296550, DOI: 10.1136/jmedgenet-2019-105991.Peer-Reviewed Original ResearchConceptsHereditary diffuse gastric cancerPathogenic variant carriersBreast cancerGastric cancerClinical criteriaCancer riskVariant carriersMultigene panel testingCancer genetics programCancer phenotypePathogenic CDH1 variantsGastric cancer riskBreast cancer familiesDiffuse gastric cancerCancer risk estimationGenotype-phenotype correlationClinical featuresCumulative cancer riskHDGC criteriaCumulative riskAge 80CDH1 variantsPanel testingClinical phenotypePathogenic variantsImplication of DNA repair genes in Lynch-like syndrome
Xicola RM, Clark JR, Carroll T, Alvikas J, Marwaha P, Regan MR, Lopez-Giraldez F, Choi J, Emmadi R, Alagiozian-Angelova V, Kupfer SS, Ellis NA, Llor X. Implication of DNA repair genes in Lynch-like syndrome. Familial Cancer 2019, 18: 331-342. PMID: 30989425, PMCID: PMC6561810, DOI: 10.1007/s10689-019-00128-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overColorectal Neoplasms, Hereditary NonpolyposisDNA MethylationDNA Mismatch RepairDNA-Binding ProteinsFemaleGerm-Line MutationHeterozygoteHumansMaleMicrosatellite InstabilityMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinSequence Analysis, DNAConceptsLLS patientsDistinct mutational signaturesGenome integrityLynch syndromeMutational signaturesMicrosatellite instabilityGermline mutationsColorectal cancerSequence analysisRepair genesSomatic MMR gene mutationsLS casesConsecutive CRC patientsMutational profileSomatic mutationsLynch-like syndromeL mutationMMR gene mutationsDNA repair genesFirst-degree relativesLikely pathogenic variantsSingle nucleotide variantsMLH1 promoter methylationTumor mutational profileExhibit microsatellite instability
2018
Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans
Xicola RM, Manojlovic Z, Augustus GJ, Kupfer SS, Emmadi R, Alagiozian-Angelova V, Triche T, Salhia B, Carpten J, Llor X, Ellis NA. Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans. Carcinogenesis 2018, 39: 1331-1341. PMID: 30239619, PMCID: PMC6292413, DOI: 10.1093/carcin/bgy122.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli ProteinBlack or African AmericanCadherinsColorectal NeoplasmsDNA Copy Number VariationsDNA MethylationDNA-Binding ProteinsExome SequencingFemaleGATA6 Transcription FactorHumansMaleMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedMixed Function OxygenasesProto-Oncogene ProteinsSOX9 Transcription FactorTranscription FactorsWnt Signaling PathwayColorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy
Murcia O, Juárez M, Rodríguez-Soler M, Hernández-Illán E, Giner-Calabuig M, Alustiza M, Egoavil C, Castillejo A, Alenda C, Barberá V, Mangas-Sanjuan C, Yuste A, Bujanda L, Clofent J, Andreu M, Castells A, Llor X, Zapater P, Jover R. Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy. PLOS ONE 2018, 13: e0203051. PMID: 30188916, PMCID: PMC6126803, DOI: 10.1371/journal.pone.0203051.Peer-Reviewed Original ResearchConceptsDisease-free survivalColorectal cancerMicrosatellite instabilityCIMP statusTNM stageKRAS mutationsBRAF mutationsMSS tumorsMolecular classificationAdvanced stage IIRetrospective observational studyPopulation-based cohortCpG island methylator phenotype (CIMP) statusCancer molecular classificationSomatic KRASAdjuvant chemotherapyAdjuvant treatmentCRC patientsPrognostic implicationsWorse prognosisPrognostic valueClinical criteriaObservational studyMolecular subtypesMAIN OUTCOMETFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer
Murcia O, Jover R, Egoavil C, Perez-Carbonell L, Juárez M, Hernández-Illán E, Rojas E, Alenda C, Balaguer F, Andreu M, Llor X, Castells A, Boland CR, Goel A. TFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer. Clinical Cancer Research 2018, 24: 2820-2827. PMID: 29535127, PMCID: PMC7396148, DOI: 10.1158/1078-0432.ccr-17-2940.Peer-Reviewed Original ResearchConceptsColorectal cancerProtein expressionClinic-based trialsStage IV patientsAdvanced colorectal cancerDisease-free survivalColorectal cancer patientsPredictors of responseClin Cancer ResColorectal cancer samplesIV patientsMulticenter cohortMethylation statusPatient cohortCancer patientsIHC analysisIHC stainingPatientsStage IICancer ResChemotherapyCancerCancer samplesCohortHypermethylation statusGenetic testing for hereditary prostate cancer: Current status and limitations
Zhen JT, Syed J, Nguyen KA, Leapman MS, Agarwal N, Brierley K, Llor X, Hofstatter E, Shuch B. Genetic testing for hereditary prostate cancer: Current status and limitations. Cancer 2018, 124: 3105-3117. PMID: 29669169, DOI: 10.1002/cncr.31316.BooksConceptsCheckpoint kinase 2Protein C-terminal helicase 1MutL homolog 1Single gene alterationsBreast cancer gene 1Next-generation sequencingHelicase 1Multiple genesAtaxia telangiectasiaKinase 2Gene 1Single gene polymorphismsHomolog 1Strong hereditary componentPostmeiotic segregationHomeobox B13NibrinBRCA1/BRCA2Hereditary componentApproval of olaparib
2017
Race-dependent association of sulfidogenic bacteria with colorectal cancer
Yazici C, Wolf PG, Kim H, Cross TL, Vermillion K, Carroll T, Augustus GJ, Mutlu E, Tussing-Humphreys L, Braunschweig C, Xicola RM, Jung B, Llor X, Ellis NA, Gaskins HR. Race-dependent association of sulfidogenic bacteria with colorectal cancer. Gut 2017, 66: 1983. PMID: 28153960, PMCID: PMC5575988, DOI: 10.1136/gutjnl-2016-313321.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedBlack or African AmericanCase-Control StudiesChicagoColonColorectal NeoplasmsDietDietary FatsDietary ProteinsFemaleHealth Status DisparitiesHumansIntestinal MucosaMaleMiddle AgedProspective StudiesReal-Time Polymerase Chain ReactionRisk FactorsSulfur-Reducing BacteriaWhite PeopleConceptsNon-Hispanic whitesEnvironmental risk factorsRisk factorsAA casesCRC casesColonic mucosaCRC developmentDisease statusAfrican AmericansCRC risk factorsUninvolved colonic mucosaColorectal cancer incidencePotential environmental risk factorsTumor-free controlsMultiple dietary componentsRace-dependent associationsEffect of dietColonic biopsiesColorectal cancerDaily servingsHealthy mucosaCancer incidenceDietary intakeProinflammatory pathwaysDiet high