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
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 progressionExpressionxDEEP-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 variants
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 ResearchMeSH KeywordsColonoscopyColorectal NeoplasmsEarly Detection of CancerHumansMass ScreeningRisk AssessmentUnited StatesConceptsColorectal 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 ResearchMeSH KeywordsAgedBlack or African AmericanChromosomes, Human, Pair 18Colorectal NeoplasmsDNA Copy Number VariationsFemaleHumansLoss of HeterozygosityMaleMiddle Aged
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 SurveyCancer
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 status
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
2016
Candidate predisposing germline copy number variants in early onset colorectal cancer patients
Brea-Fernandez AJ, Fernandez-Rozadilla C, Alvarez-Barona M, Azuara D, Ginesta MM, Clofent J, de Castro L, Gonzalez D, Andreu M, Bessa X, Llor X, Xicola R, Jover R, Castells A, Castellvi-Bel S, Capella G, Carracedo A, Ruiz-Ponte C. Candidate predisposing germline copy number variants in early onset colorectal cancer patients. Clinical And Translational Oncology 2016, 19: 625-632. PMID: 27888432, DOI: 10.1007/s12094-016-1576-z.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetColorectal NeoplasmsDNA Copy Number VariationsDNA MethylationDNA Mutational AnalysisGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansIntercellular Signaling Peptides and ProteinsLoss of HeterozygosityNerve Tissue ProteinsReal-Time Polymerase Chain ReactionConceptsColorectal cancerEarly-onset colorectal cancer patientsEarly-onset CRC patientsMethods/patientsWeColorectal cancer patientsHereditary colorectal cancerIdentifiable germline mutationsCopy number variantsPenetrant copy number variantsSomatic mutation analysisCRC patientsGenome-wide copy number analysisCancer patientsReal-time quantitative PCRMultiplex ligation probe amplificationCRC tumorsColorectal carcinogenesisLoss of heterozygosityPatientsSLIT2 geneGenetic susceptibilityDuplex real-time quantitative PCREarly onsetGermline mutationsConclusionsThese findingsA meta-analysis of MSI frequency and race in colorectal cancer
Ashktorab H, Ahuja S, Kannan L, Llor X, Ellis NA, Xicola RM, Laiyemo AO, Carethers JM, Brim H, Nouraie M. A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget 2016, 7: 34546-34557. PMID: 27120810, PMCID: PMC5085175, DOI: 10.18632/oncotarget.8945.Peer-Reviewed Original ResearchConceptsColorectal cancerMSI frequencyMicrosatellite instabilityAfrican AmericansAssociation of raceSub-group analysisMeta-regression analysisAvailable race dataClinical factorsTumor locationHigh riskMSI ratesDifferent literature databasesLiterature databasesRacial disparitiesCancerCaucasiansHispanicsDifferent studiesCaucasian samplesRandom effectsUnivariate effectsHigh frequencyRace data
2015
Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome
Santa Cruz Guindalini R, Win AK, Gulden C, Lindor NM, Newcomb PA, Haile RW, Raymond V, Stoffel E, Hall M, Llor X, Ukaegbu CI, Solomon I, Weitzel J, Kalady M, Blanco A, Terdiman J, Shuttlesworth GA, Lynch PM, Hampel H, Lynch HT, Jenkins MA, Olopade OI, Kupfer SS. Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome. Gastroenterology 2015, 149: 1446-1453. PMID: 26248088, PMCID: PMC4648287, DOI: 10.1053/j.gastro.2015.07.052.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAdultAge FactorsAgedAged, 80 and overBlack or African AmericanColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA Mismatch RepairDNA Repair EnzymesDNA-Binding ProteinsFamilyFemaleHumansIncidenceMaleMiddle AgedMismatch Repair Endonuclease PMS2MutationMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsRetrospective StudiesRisk FactorsSex FactorsConceptsColorectal cancerLynch syndromeCumulative riskRisk of CRCUS referral centersMMR gene mutationsMutation spectrumNongenetic risk factorsYears of ageMismatch repair genesMMR gene productsMutation-carrying familiesReferral centerRetrospective studyCRC riskRisk factorsFamily historyCancer riskHigh incidenceCRC conditionsSyndromeAbstractTextMMR genesAscertainment criteriaCancerEfficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer
Hamaya Y, Guarinos C, Tseng-Rogenski SS, Iwaizumi M, Das R, Jover R, Castells A, Llor X, Andreu M, Carethers JM. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer. PLOS ONE 2015, 10: e0127591. PMID: 25996601, PMCID: PMC4440728, DOI: 10.1371/journal.pone.0127591.Peer-Reviewed Original ResearchConceptsColorectal cancerStage II/III CRC patientsStage II/III colorectal cancerKaplan-Meier survival curvesSelected Tetranucleotide RepeatsSporadic colorectal cancerElevated microsatellite alterationsEMAST statusEfficacy of adjuvantsCRC patientsImproved survivalPatient outcomesSomatic dysfunctionPatientsMicrosatellite alterationsSurvival curvesCancerChemotherapySurvival dataSubsequent cytotoxicityEMASTSurvivalMMR functionSame extentCytotoxicityEnrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci
Hulur I, Gamazon ER, Skol AD, Xicola RM, Llor X, Onel K, Ellis NA, Kupfer SS. Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci. BMC Genomics 2015, 16: 138. PMID: 25766683, PMCID: PMC4351699, DOI: 10.1186/s12864-015-1292-z.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseColorectal cancerBowel diseaseSingle nucleotide polymorphismsBody mass indexType 2 diabetesHealthy African AmericansColorectal cancer risk variantsMass indexTarget genesColonic diseaseColonic samplesDiseaseNovel target geneBackgroundGenome-wide association studiesHuman colonDifferent ethnic groupsRisk variantsAfrican AmericansColonFalse discovery rateGenetic variantsNucleotide polymorphismsBiological differencesFunctional role
2014
Excess of Proximal Microsatellite-Stable Colorectal Cancer in African Americans from a Multiethnic Study
Xicola RM, Gagnon M, Clark JR, Carroll T, Gao W, Fernandez C, Mijic D, Rawson JB, Janoski A, Pusatcioglu CK, Rajaram P, Gluskin AB, Regan M, Chaudhry V, Abcarian H, Blumetti J, Cintron J, Melson J, Xie H, Guzman G, Emmadi R, Alagiozian-Angelova V, Kupfer SS, Braunschweig C, Ellis NA, Llor X. Excess of Proximal Microsatellite-Stable Colorectal Cancer in African Americans from a Multiethnic Study. Clinical Cancer Research 2014, 20: 4962-4970. PMID: 25013126, PMCID: PMC4167473, DOI: 10.1158/1078-0432.ccr-14-0353.Peer-Reviewed Original ResearchConceptsProximal colorectal cancerColorectal cancerMicrosatellite instabilityLymphocytic infiltrateKRAS mutationsAfrican AmericansMicrosatellite stable colorectal cancerDistal colorectal cancerFisher's exact testMicrosatellite stable tumorsMann-Whitney U testYoung African AmericansMedian ageAA patientsHigher BMICancer disparitiesChicago HospitalsStable tumorsAge 50High incidenceMultiethnic StudyExact testYounger ageCancerOlder age