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
Tu1100: HETEROZYGOUS MUTATIONS IN DNA REPAIR GENES CONFER GENETIC SUSCEPTIILITY TO COLORECTAL CANCER AMONG LYNCH-LIKE CASES
Giner-Calabuig M, De Leon S, Vidal-Pedrola G, Fehlmann T, Ukaegbu C, Gibson J, Picó M, Alenda C, Reyes J, Ortega S, LLado C, de la Torre Rubio P, Obrador-Hevia A, Castillejo A, Soto J, Castellví-Bel S, Syngal S, Stoffel E, Ellis N, Jover R, Llor X, Xicola R. Tu1100: HETEROZYGOUS MUTATIONS IN DNA REPAIR GENES CONFER GENETIC SUSCEPTIILITY TO COLORECTAL CANCER AMONG LYNCH-LIKE CASES. Gastroenterology 2022, 162: s-883. DOI: 10.1016/s0016-5085(22)62088-2.Peer-Reviewed Original ResearchColorectal cancerHeterozygous mutations
2021
Analysis 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 variantsDickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1
Shin JH, Jeong J, Choi J, Lim J, Dinesh RK, Braverman J, Hong JY, Maher SE, Vesely M, Kim W, Koo JH, Tang W, Wu D, Blackburn HN, Xicola RM, Llor X, Yilmaz O, Choi JM, Bothwell ALM. Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1. IScience 2021, 24: 102411. PMID: 33997693, PMCID: PMC8099562, DOI: 10.1016/j.isci.2021.102411.Peer-Reviewed Original ResearchColorectal cancerDickkopf-2Colitis-associated cancerColorectal cancer stemnessStem cell marker Lgr5Colonic epithelial cellsAggressive progressionCancer stemnessLGR5 expressionColonic organoidsCancerEpithelial cellsCell marker genesStem cell marker genesSignificant increaseGenetic depletionWnt ligandsStem cellsProgressionLgr5StemnessCellsExpressionSequential mutationsMutations
2020
Decreased 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 SurveyCancerImplication 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 statusColorectal cancer molecular classification using BRAF, KRAS, microsatellite instability, and CIMP status: Prognostic implications and response to chemotherapy.
Murcia O, Juárez M, Hernández-Illán E, Rodriguez-Soler M, Giner-Calabuig M, Alustiza M, Egoavil C, Castillejo A, Alenda C, Mangas C, Barberá V, 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. Journal Of Clinical Oncology 2018, 36: 668-668. DOI: 10.1200/jco.2018.36.4_suppl.668.Peer-Reviewed Original ResearchDisease-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 patientsWorse prognosisPrognostic implicationsPrognostic valueClinical criteriaObservational studyMolecular subtypesMAIN OUTCOME
2017
Correlations of Abdominal Fat and Colonic Sulfidogenic Bacteria in African Americans and Non‐Hispanic Whites with Newly Diagnosed Colorectal Cancer
Gomez‐Perez S, Yazici C, Wolf P, Braunschweig C, Xicola R, Llor X, Ellis N, Tussing‐Humphreys L, Mutlu E, Gaskins R. Correlations of Abdominal Fat and Colonic Sulfidogenic Bacteria in African Americans and Non‐Hispanic Whites with Newly Diagnosed Colorectal Cancer. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.138.7.Peer-Reviewed Original ResearchAbdominal fat distributionNon-Hispanic whitesNational Cancer InstituteColonic mucosaAbdominal fatWaist circumferenceColorectal cancerCancer InstitutePreoperative abdominal computed tomography scansAfrican AmericansAbdominal computed tomography scanIncident colorectal cancerComputed tomography scanGene targetsIncident CRCMean ageFat distributionTomography scanColonic tissueGut microbiotaAbundance of DesulfovibrioL3 vertebraMucosaSignificant correlationCancerRace‐dependent Association of Sulfidogenic Bacteria with Colorectal Cancer
Wolf P, Yazici C, Kim H, Liu T, Carroll T, Augustus G, Mutlu E, Tussing‐Humphreys L, Braunschweig C, Xicola R, Jung B, Llor X, Ellis N, Gaskins H. Race‐dependent Association of Sulfidogenic Bacteria with Colorectal Cancer. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.315.2.Peer-Reviewed Original ResearchNon-Hispanic whitesEnvironmental risk factorsColorectal cancerCRC casesRisk factorsAA casesFat intakeColonic mucosaCRC developmentBlock Brief 2000 food frequency questionnaireDisease statusAfrican AmericansAA controlsCRC risk factorsUninvolved colonic mucosaFood frequency questionnaireDietary fat intakePro-inflammatory pathwaysIntake of dairyTraining grantsSubset of subjectsColorectal Cancer ConsortiumNational Cancer InstituteRace-dependent associationsServings of dairyRace-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 extentCytotoxicityPrevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer
Castillejo A, Hernández-Illán E, Rodriguez-Soler M, Pérez-Carbonell L, Egoavil C, Barberá VM, Castillejo MI, Guarinos C, Martínez-de-Dueñas E, Juan MJ, Sánchez-Heras AB, García-Casado Z, Ruiz-Ponte C, Brea-Fernández A, Juárez M, Bujanda L, Clofent J, Llor X, Andreu M, Castells A, Carracedo A, Alenda C, Payá A, Jover R, Soto JL. Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer. Journal Of Medical Genetics 2015, 52: 498. PMID: 25908759, DOI: 10.1136/jmedgenet-2015-103076.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBase SequenceColorectal Neoplasms, Hereditary NonpolyposisDNA MethylationDNA Mismatch RepairEpigenesis, GeneticGenetic TestingHumansMicrosatellite RepeatsMolecular Sequence DataMutationMutL Protein Homolog 1Nuclear ProteinsPrevalencePromoter Regions, GeneticSequence Analysis, DNAStatistics, NonparametricConceptsColorectal cancerMLH1 expressionConstitutional epimutationsMultiplex ligation-dependent probe amplificationLigation-dependent probe amplificationMethylation-specific multiplex ligation-dependent probe amplificationDiagnosis of CRCConstitutional MLH1 methylationSeries of patientsMismatch repair genesProbe amplificationBethesda guidelinesConsecutive seriesUnselected seriesLynch syndromeUnselected casesUnselected groupGeneral populationUnselected populationPatientsMLH1 methylationNegligible prevalenceGermline alterationsPrevalenceMLH1 epimutations