Abel ab Susan O Hendrix ac S Gene McNeeley ac Karen C Johnson Carol A Rosenberg Yasmin MossavarRahmani Mara Vitolins and Michael Kruger ab The purpose of this study was to assess the relationship between daily coffee consumption and nonmelanoma s ID: 1424
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446ResearchpaperDailycoffeeconsumptionandprevalenceofnonmelanomaskincancerinCaucasianwomenErnestL.Abel,SusanO.Hendrix,S.GeneMcNeeleyKarenC.Johnson,CarolA.Rosenberg,YasminMossavar-RahmaniMaraVitolinsandMichaelKrugerThepurposeofthisstudywastoassesstherelationshipbetweendailycoffeeconsumptionandnonmelanomaskin eligibilitycriteriaandstudymethodshavebeenpre-viouslydescribedindetail[TheWomensHealthInitiative(WHI)StudyGroup,1998],aswellasbaselinecharacteristicsofparticipants(Langeretal.,2003).Briefly,womenofdiverseethnicbackgrounds,represent-ingthemajorethnicgroupsintheUnitedStates,whovolunteeredtoparticipate,wereeligibleifpost-menopausalattimeofenrollment.Attimeofenrollment,womencompletedscreeningandenrollmentquestion-nairesthatincludedquestionsaboutdemographicandlifestylevariables,coffeeconsumptionandhistoryofskincancer.Thequestionnairecategorizedcoffeeandteaconsumptioneachday,asnone,one,twotothree,fourtofive,orsixormorecupsperday.Respondentswerealsoaskedwhethertheyconsumedcaffeinatedcoffee,decaffeinatedcoffee,orteaforthepast3months.DataanalysisDataanalyseswerebasedoninformationobtainedatthebaselinevisit.PrevioushistoryofNMSCwasbasedonself-report.ApriorivariablesincludedintheanalyseswerethoseknownorsuspectedasbeingassociatedwithNMSC(Schottenfeld,1996;Rosenbergetal.,2004)usingthesamecriteriaorcutpointsasRosenbergetal.(2004).Theseincludedageatscreening,ethnicity(nativeAmerican,Asian,Black/African-American,Hispa-nic,White/Caucasian,other),latitudeoftheclinicwherepatientswereenrolled(Southern35N,MiddleN;Northern-174;.200;40N);bodymassindex(BMI)(25or25kg/m),historyofsmoking(current,past,nonsmoker),alcoholuse(nondrinker,pastdrinker,7or7drinksperweek),menopausalhormonetherapy(currentusers,pastusers,definedasthosereceivingtherapyfor-168;.500;3monthsbutnotreceivingtherapyattimeofinterviewandnonusers),education(highestgradecompleted:12years,highschool,somecollege,collegedegreeorpostgraduateschool),householdincome($20000,$2000049000,-168;.500;$50000),percentagedailycaloriesfromfat(30.0,30.035.0,35.140.0,-166;.600;40.0),physicalactivity(METs/week)andintake(g);thelattertwowerecategorizedintofourlevelsbasedonthe25thpercentilecut-points(025,2650,5175,-166;.600;75),havingacurrenthealthcareproviderandmaritalstatus(nevermarried,divorcedorseparated,presentlymarried).AsintheRosenbergetal.(2004)study,weconsideredwomenreportingdailyenergyintakesof600or-168;.500;5000kcal/dayasunreliableandexcludedthemfromouranalyses.Demographicandlife-stylevariables,includingdailycoffee(regularanddecaf-feinated)andteaconsumption,wereevaluatedfortheirassociationwithNMSCbytests.Samplesizeforeachanalysisdifferedbecauseofmissingdatavalues.Othersourcesofcaffeineintake(e.g.colas)werenotincludedintheregressionmodelbecauserelevantinformationwasnotavailable.StepwiselogisticregressionanalysiswasusedtoconstructadoseresponsemodelforcaffeinatedcoffeesassociationwithNMSC.Inordertoavoidthespuriouschoiceofvariablesinthemodelasaconsequenceofthelargesamplesize,weusedacriteriaofasignificantFvaluetoenterandanotherFvaluetoremovefromtheanalysesof0.01and0.05,respectively.ThedatawereanalyzedusingtheSPSS(version11.0)statisticalpackageforWindows(SPSSInc.,Chicago,Illinois,USA).Atotalof93676womenofdiverseethnicbackgrounds,16.4%ofwhomwereminority,providedbaselinedata.Overallprevalenceofself-reportedNMSCamongallwomeninthestudywas8.3%(=7775).AsthemajorityofwomeninthisstudywereCaucasian(83.6%),andnearlyallcases(97.8%)ofself-reportedNMSCoccurredamongthesewomen,andbecauseethnicitywassig-nificantlyrelatedtotheoccurrenceofNMSC=1265.3,d.f.=5,0.001),wefocusedonthissubgroupof78013women.Ofthese78013women,informationwithrespecttoself-reportedNMSCwasmissingfor638women.Afurther467(0.6%)hadmissingdatawithrespecttodailycoffeedrinking.Dailycoffeeconsumptionfortheremaining77373womenisshowninTable1;40.1%(=31048)ofthesewomenonlydrankcaffeinatedcoffee,15.0%(=11597)onlydrankdecaffeinatedcoffee,16.5%(=12759)drankbothcaffeinatedanddecaffeinatedcoffee,and28.4%=21969)reporteddrinkingnocoffee.Therelationshipbetweendemographic/lifestylevari-ablesandNMSCisshowninTable2.LatitudeofresidencewassignificantlyassociatedwithNMSC;thehighestprevalenceoccurredamongwomenlivinginthesouthernmostlatitude(12.6%)andthelowestinthenorthernmostlatitude(7.6%).HigherBMI25)wasalsosignificantlyassociatedwithNMSC.Thehighertheeducationandincomelevels,thehighertheprevalenceofNMSC.SmokingandalcoholconsumptionwerebothsignificantlyassociatedwithNMSC.PastorcurrentusersofmenopausalhormonereplacementtherapyhadahigherprevalenceofNMSCthannonusers,butonlythedifferencesbetweenpastusersorcurrentusers,andneverusersweresignificant(0.001foreach).PhysicalactivitywaspositivelyassociatedwiththeprevalenceofNMSCwhereaspercentageofdailydietarycaloriesfromfatwasnegativelyrelated.Beta-caroteneintakewassignificantlyrelatedtoNMSCbuttheassociationwithNMSCwasnotlinear.Therelationshipbetweendailycaffeinatedcoffeecon-sumptionandNMSCisshowninTable3.Drinkingcaffeinatedcoffeewasassociatedwithadecreasedprevalenceofself-reportedNMSCcomparedwithnon-drinkers(9.1vs.10.2%,respectively).ThisassociationCoffeeandcanceretal.447 caffeinatedcoffeeconsumptionandtheriskofNMSCwasstatisticallysignificant(0.001).AschroniccumulativeexposuretosolarultravioletradiationisthemostimportantfactorassociatedwithNMSC(TaylorandSober,1996),wealsotestedforaninteractionbetweencupsofcaffeinatedcoffeeandlatitude,forriskofNMSC.Theinteractionwasnotstatisticallysignificant.WealsoconductedasubgroupanalysisoftherelationshipbetweencoffeeconsumptionandNMSCstratifyingforhistoriesofothercancers.TherelationshipbetweencaffeinatedcoffeeconsumptionandNMSCwasnotsignificantforwomenwithahistoryofcancerotherthanNMSC.Asignificantdoseresponserelationship,however,wasstillevidentforthosewomenwithoutahistoryofothercancers.Theoddsratioforsixormoreforthelattercupswas0.70(confidenceinterval:0.560.89,0.001). Table2Demographic/lifestylevariablesandriskofnonmelanomaskincancerCrudeORUnadjustedORVariableCategoryOR95%CIOR95%CIAge(years)505960691.05(1.011.10)1.05(1.021.09)70791.45(1.381.52)1.44(1.391.49)AlcoholNondrinkerPastdrinker1.09(0.941.27)1.03(0.931.14)7drinksperweek1.24(1.091.42)1.08(0.991.18)-171;.200;7drinksperweek1.38(1.191.60)1.20(1.081.33)Education12yearsHighschooldegree1.31(1.031.65)1.13(0.951.34)Afterhighschool1.59(1.272.00)1.43(1.221.68)Collegedegree1.90(1.522.39)1.74(1.482.04)HormonereplacementtherapystatusNeverusedPastuser1.17(1.071.28)1.20(1.121.29)Currentuser1.04(0.971.11)1.04(0.991.09)RegionSouthernMiddle0.99(0.951.04)1.00(0.971.04)Northern0.76(0.730.80)0.76(0.730.78)Bodymassindex25250.89(0.830.94)0.81(0.770.85)Caloriesfromfat(%)3030351.03(0.941.13)1.00(0.941.06)35.1401.05(0.961.15)0.94(0.881.01)-171;.300;401.19(1.081.30)0.85(0.790.91)OR,oddsratio;CI,confidenceinterval. Table3DailycaffeinatedcoffeedrinkingandriskofnonmelanomaskincanceramongCaucasianwomen(77373)PercentagePercentagewithskincancerOddsratio95%ConfidenceintervalUnadjustedoddsratio3356843.410.31.011258416.310.20.96(0.891.03)0.99(0.921.05)232313329.99.10.87(0.810.92)0.87(0.820.92)4563528.28.10.83(0.750.92)0.76(0.690.84)6ormore17382.26.70.70(0.600.88)0.63(0.520.76)Total773759.7Oddsratiovariablesincludedinstepwiseregressionmodel:ageatscreening,alcoholconsumption,smoking,income,regionofresidencebylatitude,education,menopausalhormonetherapy,bodymassindex,and-caroteneintake.Unadjustedoddsratiobasedoncupsofregularcoffeeastheonlypredictorinthemodel.Drinkseithernocoffeeordecaffeinatedcoffeeonly. Table4Dailyintakeofdecaffeinatedcoffeeandteaandunadjustedoddsratio(OR)ofnonmelanomaskincancer(NMSC)riskDecaffeinatedcoffeeTeaPercentagePercentageNMSCOR95%CICupsPercentagePercentageNMSCOR95%CI02977754.39.105639173.99.611153721.010.01.121.041.201965312.610.11.060.991.14231080319.710.11.131.051.2223810510.611.01.050.971.144522464.18.80.960.831.124516832.29.10.950.801.1264830.99.71.080.801.4664880.68.20.840.611.17Total548469.5Total763209.7CI,confidenceinterval.Coffeeandcanceretal.449 manywomenintheyearspriortoassessment,thedietaryinformationrecordedatenrollmentmaynotreflectgeneralpatternsofdietoverthelifespan.Denialandunder-reportingalsohastobeconsideredinthecontextofsmokingandalcoholuse(Abel,1998).We,however,arenotawareofanydatasuggestingdifferentialunder-reportingofeithersmokingoralcoholuseinwomenwithandwithoutNMSC.Informationaboutcoffeeandteausemayalsobeproblematicaswomenwereaskedtorecalltheirlevelsofdailyconsumptionatthetimeofenrollmentandconsumptionlevelsmayhavenotbeensimilaratthetimewomenwerediagnosedwithskincancer.Despitethesecaveats,thedecreasedprevalenceinNMSCassociatedwithconsumptionofdailyconsump-tionofcaffeinatedcoffeethatweobservedwasdose-relatedandconsistentwithotherstudies.AmongthepossibleexplanationsforcaffeinesprotectiveeffectonNMSCthathavebeensuggestedisanantioxidanteffect(Kuo,1997;TrevisanatoandKim,2000)and/orinhibitionofDNAsynthesisandcelldivision,makingcellslesssusceptibletocarcinogenesis(Timson,1997).Weconcludethatdailycaffeinatedcoffeeconsumptionisassociatedwithadose-relateddecreasedprevalenceofNMSCinCaucasianwomen.Ideally,theobservationsreportedhereandourconclusionshouldbeexploredinfutureprospectivestudies.AcknowledgementsTheWHIprogramisfundedbytheNationalHeart,LungandBloodInstitute,USDepartmentofHealthandHumanServices.AbelEL(1998).Fetalalcoholabusesyndrome.NewYork:PlenumPress.AubryF,MacGibbonB(1985).Riskfactorsofsquamouscellcarcinomaoftheskin:acase-controlstudyintheMontrealregion.:907911.BlackHS(1998).Influenceofdietaryfactorsonactinically-inducedskincancer.MutatRes:185190.CoronaR,DogliottiE,DErricoM,SeraF,LevaroneI,BalivaG,etal.(2001).RiskfactorsforbasalcellcarcinomainaMediterraneanpopulation:roleofrecreationalsunexposureearlyinlife.ArchDermatol:11621168.DeHertogSAE,WensveenCAH,BastiaensMT,KiehichCJ,BerkhoutMJP,WestendorpRGJ,etal.(2001).Relationbetweensmokingandskincancer.JClinOncol:231238.FraryCF,JohnsonRK,WangMQ(2005).FoodsourcesandintakesofcaffeineinthedietsofpersonsintheUnitedStates.JAmDietAssocGrodsteinF,SpeizerFE,HunterDJ(1995).Aprospectivestudyofincidentsquamouscellcarcinomaoftheskininthenurseshealthstudy.JNatlCancerInst:10611066.HuangM-T,XieJ-G,WangZY,HoCT,LouYR(1997).CarcinogenesisinSKH-1mice:demonstrationofcaffeineasabiologicallyimportantconstituentoftea.CancerRes:26232629.JacobsenBK,BjelkeR,KvaleG,HeuchI(1986).Coffeedrinking,mortality,andcancerincidence:resultsfromaNorwegianprospectivestudy.JNatlCancer:823834.JohnsonML,JohnsonKG,EngelA(1984).Prevalence,morbidity,andcostofdermatologicdiseases.JAmAcadDermatol:930936.KaaksR,LukanovaA,KurzerMS(2002).Obesity,endogenoushormones,andendometrialcancerrisk.Asyntheticreview.CancerEpidemiolBiomarkers:15311543.KuoSM(1997).Dietaryflavonoidandcancerprevention:evidenceandpotentialCritRevOncol:4769.LangerRD,WhiteE,LewisCE,KotchenJ,HendrixS,TrevisanM(2003).TheWomensHealthInitiativeObservationalStudy:baselinecharacteristicsofparticipantsandreliabilityofbaselinemeasures.AnnEpidemiolS107S121.MarksR(1996).Squamouscellcarcinoma.347:735738.MichelsKB,HolmbergL,BergkvistL,WolkA(2002).Coffee,tea,andcaffeineconsumptionandbreastcancerincidenceinacohortofSwedishwomen.AnnEpidemiolMingME,RossR,LevyRM,OleJ,HoffstadMA,FilipJ,etal.(2004).Validityofpatientselfreportedhistoryofskincancer.ArchDermatol140:730735.RiboliE(2001).TheEuropeanprospectiveinvestigationintocancerandnutrition(EPIC):plansandprogress.JNutr131:170S175S.RosenbergCA,GreenlandP,KhandekarJ,LoarA,AscensaoJ,LopezAM(2004).Associationofnonmelanomaskincancerwithsecondmalignancy.TheWomensHealthInitiativeObservationalStudy.100:130138.SchottenfeldD(1996).Basal-cellcarcinomaoftheskin:aharbingerofcutanenousandnoncutaneousmultipleprimarycancer(editorial).AnnIntern:852854.StromSS,YamamuraY(1997).Epidemiologyofnonmelanomaskincancer.PlastSurg:627636.TavaniA,LaVecchiaC(2000).Coffeeandcancer:areviewofepidemiologicalstudies,19901999.EurJCancerPrevent:241256.TaylorCR,SoberAJ(1996).Sunexposureandskindisease.AnnRevMedTheWomensHealthInitiative(WHI)StudyGroup(1998).DesignoftheWomensHealthInitiativeclinicaltrialandobservationalstudy.ControlClinTrials:61109.TimsonJ(1997).Caffeine.MutatResTrevisanatoS,KimYI(2000).Teaandhealth.NutrRevVeierodMB,ThelleDS,LaakeP(1997).Dietandriskofcutaneousmalignantmelanoma:aprospectivestudyof50757Norwegianmenandwomen.IntJ:600604.VonDomarusH,StevensPJ(1984).Metastaticbasalcellcarcinoma:reportoffivecasesandreviewof170casesintheliterature.JAmAcadDermatol:10431060.WangZY,AgarwalR,BickersDR,MukhtarH(1991).ProtectionagainstultravioletBradiation-inducedphotocarcinogenesisinhairlessmicebygreenteapolyphenols.WangZY,HuangM-T,FerraroT,WongCQ,LouYR,ReuhlK,etal.(1992).Inhibitoryeffectofgreenteaindrinkingwaterontumorigenesisbyultravioletlightand12--tetradecanolylphorbol-13-acetateintheskinofSKH-1mice.CancerRes:11621170.WangZY,HuangMT,LouY-R,XieJG,ReuhlKR,NewmarkHL,etal.(1994).Inhibitoryeffectsofblacktea,greentea,decaffeinatedblacktea,anddecaffeinatedgreenteaonultravioletBlight-inducedskincarcinogenesisin7,12-dimethylbenz(a)anthracene-initiatedSKH-1mice.CancerRes34283435.WebbAR,Kl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