2020
Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
Shuch B, Li S, Risch H, Bindra RS, McGillivray PD, Gerstein M. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer. Cancer 2020, 126: 3657-3666. PMID: 32413184, PMCID: PMC10316675, DOI: 10.1002/cncr.32914.Peer-Reviewed Original ResearchConceptsFumarate hydrataseExome Aggregation ConsortiumAllele frequenciesFH geneGenome ProjectDifferent world populationsFH alterationsHereditary leiomyomatosisKidney cancer riskCancer penetranceMissense alterationsGenesOverall allele frequencyRare variantsLow penetranceRenal cancerExACKidney cancerCancer riskPenetranceGermline mutationsLethal formWorld populationCancer syndromesAlterations
2017
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study
Haycock P, Burgess S, Nounu A, Zheng J, Okoli G, Bowden J, Wade K, Timpson N, Evans D, Willeit P, Aviv A, Gaunt T, Hemani G, Mangino M, Ellis H, Kurian K, Pooley K, Eeles R, Lee J, Fang S, Chen W, Law M, Bowdler L, Iles M, Yang Q, Worrall B, Markus H, Hung R, Amos C, Spurdle A, Thompson D, O’Mara T, Wolpin B, Amundadottir L, Stolzenberg-Solomon R, Trichopoulou A, Onland-Moret N, Lund E, Duell E, Canzian F, Severi G, Overvad K, Gunter M, Tumino R, Svenson U, van Rij A, Baas A, Bown M, Samani N, van t’Hof F, Tromp G, Jones G, Kuivaniemi H, Elmore J, Johansson M, Mckay J, Scelo G, Carreras-Torres R, Gaborieau V, Brennan P, Bracci P, Neale R, Olson S, Gallinger S, Li D, Petersen G, Risch H, Klein A, Han J, Abnet C, Freedman N, Taylor P, Maris J, Aben K, Kiemeney L, Vermeulen S, Wiencke J, Walsh K, Wrensch M, Rice T, Turnbull C, Litchfield K, Paternoster L, Standl M, Abecasis G, SanGiovanni J, Li Y, Mijatovic V, Sapkota Y, Low S, Zondervan K, Montgomery G, Nyholt D, van Heel D, Hunt K, Arking D, Ashar F, Sotoodehnia N, Woo D, Rosand J, Comeau M, Brown W, Silverman E, Hokanson J, Cho M, Hui J, Ferreira M, Thompson P, Morrison A, Felix J, Smith N, Christiano A, Petukhova L, Betz R, Fan X, Zhang X, Zhu C, Langefeld C, Thompson S, Wang F, Lin X, Schwartz D, Fingerlin T, Rotter J, Cotch M, Jensen R, Munz M, Dommisch H, Schaefer A, Han F, Ollila H, Hillary R, Albagha O, Ralston S, Zeng C, Zheng W, Shu X, Reis A, Uebe S, Hüffmeier U, Kawamura Y, Otowa T, Sasaki T, Hibberd M, Davila S, Xie G, Siminovitch K, Bei J, Zeng Y, Försti A, Chen B, Landi S, Franke A, Fischer A, Ellinghaus D, Flores C, Noth I, Ma S, Foo J, Liu J, Kim J, Cox D, Delattre O, Mirabeau O, Skibola C, Tang C, Garcia-Barcelo M, Chang K, Su W, Chang Y, Martin N, Gordon S, Wade T, Lee C, Kubo M, Cha P, Nakamura Y, Levy D, Kimura M, Hwang S, Hunt S, Spector T, Soranzo N, Manichaikul A, Barr R, Kahali B, Speliotes E, Yerges-Armstrong L, Cheng C, Jonas J, Wong T, Fogh I, Lin K, Powell J, Rice K, Relton C, Martin R, Smith G. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncology 2017, 3: 636-651. PMID: 28241208, PMCID: PMC5638008, DOI: 10.1001/jamaoncol.2016.5945.Peer-Reviewed Original ResearchConceptsGermline genetic variationGenomewide association studiesGenetic variationSingle nucleotide polymorphismsTelomere lengthStem cell divisionSummary association statisticsGermline genetic variantsCell divisionAssociation studiesLonger telomeresGenetic variantsNucleotide polymorphismsAssociation statisticsTelomeresSummary dataLung adenocarcinomaKidney cancerNon-neoplastic diseasesPolymorphismVariationTissue sitesCancerOvarian cancerDivisionCorrelation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens
Akbari MR, Zhang S, Cragun D, Lee JH, Coppola D, McLaughlin J, Risch HA, Rosen B, Shaw P, Sellers TA, Schildkraut J, Narod SA, Pal T. Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens. Familial Cancer 2017, 16: 351-355. PMID: 28176205, DOI: 10.1007/s10689-017-9973-1.Peer-Reviewed Original ResearchConceptsOvarian cancer specimensOvarian cancerCancer specimensMicrosatellite instabilityGermline mutationsMMR mutationsMSI testingGermline MMR gene mutationsMMR genesPathogenic MMR mutationsMalignant ovarian cancerMMR gene mutationsPositive predictive valueMismatch repair genesMSI-positive cancersLynch syndromeMore microsatellite markersUnselected casesPredictive valuePatientsCancerPotential patientsGermline DNAGene mutationsWomen
2016
Frequency of germline PALB2 mutations among women with epithelial ovarian cancer
Kotsopoulos J, Sopik V, Rosen B, Fan I, McLaughlin JR, Risch H, Sun P, Narod SA, Akbari MR. Frequency of germline PALB2 mutations among women with epithelial ovarian cancer. Familial Cancer 2016, 16: 29-34. PMID: 27631815, DOI: 10.1007/s10689-016-9919-z.Peer-Reviewed Original ResearchConceptsGermline PALB2 mutationsPALB2 mutationsOvarian cancerEpithelial ovarian cancer patientsYear of diagnosisEpithelial ovarian cancerOvarian cancer patientsOvarian cancer riskMean ageCancer patientsControl subjectsNational HeartMedical recordsClinical recommendationsSurvival statusCancer riskClinical informationUnselected populationClinical relevanceBRCA2 genesGermline mutationsCancerFurther studiesPatientsPrevalenceGermline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma
Buas MF, He Q, Johnson LG, Onstad L, Levine DM, Thrift AP, Gharahkhani P, Palles C, Lagergren J, Fitzgerald RC, Ye W, Caldas C, Bird NC, Shaheen NJ, Bernstein L, Gammon MD, Wu AH, Hardie LJ, Pharoah PD, Liu G, Iyer P, Corley DA, Risch HA, Chow WH, Prenen H, Chegwidden L, Love S, Attwood S, Moayyedi P, MacDonald D, Harrison R, Watson P, Barr H, deCaestecker J, Tomlinson I, Jankowski J, Whiteman DC, MacGregor S, Vaughan TL, Madeleine MM. Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Gut 2016, 66: 1739. PMID: 27486097, PMCID: PMC5296402, DOI: 10.1136/gutjnl-2016-311622.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBarrett EsophagusCytokinesEsophageal NeoplasmsFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyGerm-Line MutationGlutathione TransferaseHLA AntigensHumansInflammationMaleMiddle AgedNF-kappa BOxidative StressPolymorphism, Single NucleotidePrincipal Component AnalysisProstaglandin-Endoperoxide SynthasesRisk FactorsSignal TransductionConceptsBarrett's esophagusBE casesSingle nucleotide polymorphismsGermline variationOesophageal adenocarcinoma incidenceHuman leucocyte antigenInflammation-related pathwaysSymptomatic refluxSystemic inflammationAdenocarcinoma incidenceOesophageal adenocarcinomaOA pathogenesisInflammatory processLeucocyte antigenOA casesRisk factorsCOX pathwayBE riskOA riskDisease riskEsophagusStrong expression quantitative trait locusGenetic susceptibilityNuclear factorExpression quantitative trait loci
2013
Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux
Ek WE, Levine DM, D’Amato M, Pedersen NL, Magnusson PK, Bresso F, Onstad LE, Schmidt PT, Törnblom H, Nordenstedt H, Romero Y, , Chow W, Murray L, Gammon M, Liu G, Bernstein L, Casson A, Risch H, Shaheen N, Bird N, Reid B, Corley D, Hardie L, Ye W, Wu A, Zucchelli M, Spector T, Hysi P, Vaughan T, Whiteman D, MacGregor S. Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux. Journal Of The National Cancer Institute 2013, 105: 1711-1718. PMID: 24168968, PMCID: PMC3833931, DOI: 10.1093/jnci/djt303.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedBarrett EsophagusCase-Control StudiesChromosome DisordersEsophageal NeoplasmsFemaleGastroesophageal RefluxGenome-Wide Association StudyGerm-Line MutationHumansMaleMiddle AgedPolymorphism, Single NucleotidePredictive Value of TestsPrevalenceRisk AssessmentRisk FactorsSex FactorsSoftwareTwin Studies as TopicPolymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4
Leenders M, Bhattacharjee S, Vineis P, Stevens V, Bueno-de-Mesquita HB, Shu XO, Amundadottir L, Gross M, Tobias GS, Wactawski-Wende J, Arslan AA, Duell EJ, Fuchs CS, Gallinger S, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, Kooperberg C, LaCroix A, Li D, Mandelson MT, Olson SH, Petersen G, Risch HA, Yu K, Wolpin BM, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovanucci EL, Goggins M, Hallmans G, Hankinson SE, Hoffman-Bolton JA, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, Rabe KG, Riboli E, Tjønneland A, Trichopoulos D, Virtamo J, Visvanathan K, Elena JW, Yu H, Zeleniuch-Jacquotte A, Stolzenberg-Solomon RZ. Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4. Cancer Causes & Control 2013, 24: 595-602. PMID: 23334854, PMCID: PMC4127987, DOI: 10.1007/s10552-012-0138-0.Peer-Reviewed Original ResearchMeSH KeywordsCarbonCase-Control StudiesCohort StudiesGerm-Line MutationHumansPancreatic NeoplasmsPolymorphism, Single NucleotideUnited StatesConceptsCase-control studyOne-carbon metabolismSingle nucleotide polymorphismsPancreatic cancerOne-carbon biomarkersEuropean Prospective InvestigationCorrelation of SNPsProspective InvestigationFolate intakePancreatic carcinogenesisLarge genetic studiesGene polymorphismsSignificant associationPANCACancerMetabolite levelsGermline variationP-valueMultiple comparisonsAssociationSuggestive associationPolymorphismSuggestive evidenceMetabolismOCM pathway
2011
Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer
Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, Fan I, Bradley L, Shaw PA, Narod SA. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecologic Oncology 2011, 121: 353-357. PMID: 21324516, DOI: 10.1016/j.ygyno.2011.01.020.Peer-Reviewed Original ResearchConceptsInvasive ovarian cancerOvarian cancerFirst-degree relativesMultiplex ligation-dependent probe amplificationUnselected patientsBRCA2 mutationsNon-mucinous ovarian cancerGermline mutationsCombined mutation frequencyPopulation-based seriesOvarian cancer patientsCommon adult cancersSerous ovarian cancerPrevalence of mutationsFrequency of BRCA1Mucinous carcinomaCancer patientsAdult cancersLigation-dependent probe amplificationCancerGenetic testingPatientsWomenBreastBRCA1
2009
Polymorphic Variation of Genes in the Fibrinolytic System and the Risk of Ovarian Cancer
Bentov Y, Brown TJ, Akbari MR, Royer R, Risch H, Rosen B, McLaughlin J, Sun P, Zhang S, Narod SA, Casper RF. Polymorphic Variation of Genes in the Fibrinolytic System and the Risk of Ovarian Cancer. PLOS ONE 2009, 4: e5918. PMID: 19526059, PMCID: PMC2691597, DOI: 10.1371/journal.pone.0005918.Peer-Reviewed Original ResearchConceptsOvarian cancerSingle nucleotide polymorphismsCandidate genesFibrinolytic systemGenesFunctional variantsFunctional SNPsNucleotide polymorphismsPolymorphic variationBlood clot degradationOvarian cancer casesFunctional effectsSNPsHistologic subgroupsRetrograde menstruationCancer casesClot degradationGenotype distributionBlood clotsSignificant associationCancerFibrin productsGermlineInefficient removalRisk
2008
Uptake of clinical genetic testing for ovarian cancer in Ontario: A population-based study
Metcalfe KA, Fan I, McLaughlin J, Risch HA, Rosen B, Murphy J, Bradley L, Armel S, Sun P, Narod SA. Uptake of clinical genetic testing for ovarian cancer in Ontario: A population-based study. Gynecologic Oncology 2008, 112: 68-72. PMID: 19019415, PMCID: PMC3074978, DOI: 10.1016/j.ygyno.2008.10.007.Peer-Reviewed Original ResearchConceptsInvasive ovarian cancerClinical genetic testingOvarian cancerGenetic testingGenetic test resultsBlood samplesPositive genetic test resultOntario Cancer RegistryPopulation-based studyEpithelial ovarian cancerProportion of womenCancer RegistryRisk factorsBRCA2 mutationsClinical testingCancerWomenBRCA2BRCA1Small proportionPrevious testingMutationsPatientsTestingRegistry
2002
Histopathologic Features of Genetically Determined Ovarian Cancer
Shaw P, McLaughlin J, Zweemer R, Narod S, Risch H, Verheijen R, Ryan A, Menko F, Kenemans P, Jacobs I. Histopathologic Features of Genetically Determined Ovarian Cancer. International Journal Of Gynecological Pathology 2002, 21: 407-411. PMID: 12352190, DOI: 10.1097/00004347-200210000-00011.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGenes, BRCA1Genes, BRCA2Genetic Predisposition to DiseaseGerm-Line MutationHumansOvarian NeoplasmsPrognosisRisk FactorsConceptsInvasive serous carcinomasOvarian carcinomaSilverberg gradeGermline mutationsHistologic typeSerous carcinomaNuclear gradeGOG grade 3High histologic gradeBRCA1/BRCA2Serous histologyGynecologic pathologistsHistologic featuresHistopathologic featuresBRCA carriersHistologic gradeBRCA mutationsOvarian cancerArchitectural gradeBRCA2 mutationsGrade 3Germline BRCA1CarcinomaMutation statusControl group
2001
Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives
Runnebaum I, Wang-Gohrke S, Vesprini D, Kreienberg R, Lynch H, Moslehi R, Ghadirian P, Weber B, Godwin A, Risch H, Garber J, Lerman C, Olopade O, Foulkes W, Karlan B, Warner E, Rosen B, Rebbeck T, Tonin P, Dubé M, Kieback D, Narod S. Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics And Genomics 2001, 11: 635-638. PMID: 11668223, DOI: 10.1097/00008571-200110000-00010.Peer-Reviewed Original ResearchConceptsPROGINS alleleOvarian cancerOral contraceptivesBRCA2 mutationsCarriers of BRCA1Oral contraceptive useOvarian cancer riskHereditary ovarian cancerBRCA2 mutation carriersOral contraception useForms of cancerYear of birthPrior diagnosisBRCA2 carriersProgesterone receptorBreast cancerMutation carriersContraceptive useCancer riskContraception useHereditary breastDisease statusPast exposureCancerBRCA1 mutationsPrevalence and Penetrance of Germline BRCA1 and BRCA2 Mutations in a Population Series of 649 Women with Ovarian Cancer
Risch H, McLaughlin J, Cole D, Rosen B, Bradley L, Kwan E, Jack E, Vesprini D, Kuperstein G, Abrahamson J, Fan I, Wong B, Narod S. Prevalence and Penetrance of Germline BRCA1 and BRCA2 Mutations in a Population Series of 649 Women with Ovarian Cancer. American Journal Of Human Genetics 2001, 68: 700-710. PMID: 11179017, PMCID: PMC1274482, DOI: 10.1086/318787.Peer-Reviewed Original ResearchConceptsOvarian cancer cluster regionFirst-degree relativesOvarian cancerBRCA2 mutationsProtein truncation testBRCA1 mutationsInvasive cancerBreast cancerAffected first-degree relativeRelatives of noncarriersRisk of ovarianPopulation-based seriesAge 80 yearsBreast cancer riskHereditary ovarian cancerBreast cancer penetranceEarly-onset diseaseLate-onset cancerLeukemia/lymphomaRelatives of casesMutation locationExon 11Borderline histologyIncident casesColorectal cancer
1999
Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations
Wang-Gohrke S, Weikel W, Risch H, Vesprini D, Abrahamson J, Lerman C, Godwin A, Moslehi R, Olipade O, Brunet J, Stickeler E, Kieback D, Kreienberg R, Weber B, Narod S, Runnebaum I. Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations. British Journal Of Cancer 1999, 81: 179-183. PMID: 10487631, PMCID: PMC2374363, DOI: 10.1038/sj.bjc.6690669.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsBRCA2 germline mutationsCancer patientsOvarian cancerP53 geneGermline mutationsCarriers of BRCA1Breast-ovarian cancer familiesRisk-modifying effectBRCA2 mutation carriersBp duplication polymorphismUnaffected female carriersRestriction fragment length polymorphismDeleterious BRCA1Healthy controlsBRCA2 mutationsMutation carriersCancer familiesPatientsFemale carriersGermline DNACancerIntronic polymorphismDuplication polymorphismMspI restriction fragment length polymorphismAccumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations.
Zweemer R, Shaw P, Verheijen R, Ryan A, Berchuck A, Ponder B, Risch H, McLaughlin J, Narod S, Menko F, Kenemans P, Jacobs I. Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations. Journal Of Clinical Pathology 1999, 52: 372. PMID: 10560359, PMCID: PMC1023075, DOI: 10.1136/jcp.52.5.372.Peer-Reviewed Original ResearchConceptsOvarian cancer casesBRCA2 germline mutationsHereditary ovarian cancerOvarian cancerCancer casesP53 accumulationGermline mutationsSomatic genetic eventsInvasive ovarian cancer casesBRCA2 germline mutation carriersOvarian cancer patientsP53 proteinGermline mutation carriersGenetic eventsRole of p53Cancer patientsAntigen retrieval techniqueBRCA mutationsBRCA2 mutationsStudy groupMutation carriersP53 alterationsP53 immunohistochemistryGermline BRCA1Positive cases
1998
Oral Contraceptives and the Risk of Hereditary Ovarian Cancer
Narod S, Risch H, Moslehi R, Dørum A, Neuhausen S, Olsson H, Provencher D, Radice P, Evans G, Bishop S, Brunet J, Ponder B, Klijn J. Oral Contraceptives and the Risk of Hereditary Ovarian Cancer. New England Journal Of Medicine 1998, 339: 424-428. PMID: 9700175, DOI: 10.1056/nejm199808133390702.Peer-Reviewed Original ResearchConceptsOral contraceptive useHereditary ovarian cancerOvarian cancerOral contraceptivesControl womenBRCA2 genesPathogenic mutationsCase-control studyHigh lifetime riskDuration of useYear of birthLifetime riskOdds ratioBRCA2 mutationsLifetime historyHereditary formsCancerBRCA1 mutationsContraceptivesWomenPatientsRiskMore yearsPast useBRCA1