Lifestyle and family history influence cancer prognosis in Brazilian individuals

ContentslistsavailableatScienceDirect

Pathology

–

Research

and

Practice

jo u r n al ho me p a g e :w w w . e l s e v i e r . c o m / l o c a t e / p r p

Original

Article

Lifestyle

and

family

history

influence

cancer

prognosis

in

Brazilian

individuals

Raimundo

F.

Araújo

Jr.

_,

_George

_A.

_Lira

_,

_Hugo

_G.

_Guedes

_,

_Marília

_A.

_Cardoso

_,

Francisco

J.

Cavalcante

_,

_Ana

_Lucia

_M.

_Araújo

_,

_Carlos

_César

_O.

_Ramos

_,

Aurigena

Antunes

de

Araújo

a_{PostGraduationPrograminFunctionalandStructuralBiology,UFRN,Natal,RN,Brazil} b_{PostGraduationProgramHealthScience,UFRN,Natal,RN,Brazil}

c_{DepartmentofMorphology,UFRN,Natal,RN,Brazil}

d_{ClinicalDecisionUnit,DepartmentofAcuteMedicine,StThomas’sHospital,WestminsterBridgeRoad,SE17EHLondon,England,UnitedKingdom} e_{LigaNorteRiograndenseContraoCâncer,Natal,RN,Brazil}

f_{PostgraduationPrograminPublicHealth,UFRN,Natal,RN,Brazil} g_{PostgraduationPrograminPharmaceuticalScience,UFRNNatal,RN,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received19March2013

Receivedinrevisedform12July2013 Accepted7August2013 Keywords: Colorectalcancer Brazil Survival Neoplasmbysite Publichealth

a

b

s

t

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TheaimofthisresearchwastostudyprognosticparametersofCRCbyanalyzingclinicalandpathological variablesassociatedwithcancerpatientsatanortheasternBrazilianHospital.

ThiswasaretrospectivestudyevaluatingCRC-diagnosedpatientsacrossa10-yearperiod(1995–2005) atDr.LuizAntônioHospitalinNatal,RN,Brazil.Datawerecollectedfrompatients’medicalfiles.

Atotalof358patientswereincludedoverthe10-yearperiod.Theaverageageatdiagnosiswas58.8 years(S.D.=15.26),48.3%ofthepatientsweremalesand51.7%werefemales.Alcoholconsumption significantlyincreasedthechanceofdying(p<0.023)fromcolorectalcancer;thisincreasedriskofdeath wasapproximately71%,comparedto52.2%ofthenon-alcoholics.Inaddition,tobaccoincreasedthe chanceofdevelopinghighTNMstagetumors(levelIII,IV;p<0.001).Anotherriskfactorforincreased mortalitywasafamilyhistoryforcolorectalcancer(p<0.002).

Ouranalysisfoundthatpatientswithanunhealthylifestyleand/orfamilyhistoryofcolorectalcancer weremorelikelytodevelopadvancedstagecolorectalcancerandtohaveapoordiseaseprognosis comparedtopatientswithhealthylifestyleand/orsporadiccolorectalcancer.Thesedatasuggestthata massscreeningprogramshouldbeimplementedinnortheasternBrazilinordertobetterpreventand treatcolorectalcancer.

© 2013 Elsevier GmbH. All rights reserved.

Introduction

Excludingnon-melanomaskintumors,malecancerofthecolon

andrectumisthesecondmostcommoncancerinthesoutheastof

Brazil(22/100000)andthirdinthesouthernregion(18/100000)

andmid-westernregion(14/100000).Itranksfourthinthenorthof

Brazil(4/100000),andfifthinthenortheasternregion(5/100000).

Forfemales,cancerofthecolon andrectumisthesecondmost

frequent tumor in the southeastern(23/100000) and southern

region(20/100000).ItcomesthirdintheMidwest(15/100000)and

Northeast(7/100000),anditissixthinnorthernBrazil(5/100000)

[1].Inanortheasterncity,Fortaleza/CearáState,1019newcases

∗ Correspondingauthorat:PostGraduationPrograminFunctionalandStructural Biology,UFRN,Natal,RN,Brazil.

E-mailaddress:aurigena@ufrnet.br(R.F.AraújoJr.).

werediagnosedfrom1990to1999(475male/544female).The

mean age-specificcolorectal cancerincidencerates for1990 to

1999 show that the disease incidence begins to appear in the

50–59-year-oldagegroupinbothgendersinFortaleza[2].

TheAmericanCancerSocietyhasapre-establishedscreeningfor

colorectalcancerthatbasicallyrecommendscolonoscopyevery10

yearsorearlyfecalbloodtestor/plusflexiblesigmoidoscopyevery

5years,andtobeginscreeningat50yearsofageormoreyounger

ifthereisafamilialriskfactor[3].

Cigarettesmokingcausesmanynon-pulmonarycancers,

includ-ing those of the oral cavity, pancreas, and kidney. However,

theassociationbetweensmokingandCRCremainscontroversial.

While many earlystudiesfailed tofinda relationship between

cigaretteuseageandCRC,researchpublishedafter1970supports

anassociationbetweenthesevariables.Oneexplanationforthe

discrepancybetweenthefindingsmaybethe35-to40-yearlag

timebetweenexposureanddisease,whichwouldnothavebeen

0344-0338/$–seefrontmatter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.08.007

capturedbyearlierstudiesorthosewithshort-termfollowup.

Irre-spectiveofthis,neithertheInternationalAgencyforResearchon

Cancer(IARC)northeU.S.SurgeonGeneralrecognizessmokingas

ariskfactorforCRC[4].

Nevertheless,smokingmayaltergeneexpression,whichmay

then influence one’s health. For example, tobacco smoke

con-tainsvarious typesof carcinogens, suchas polycyclic aromatic

hydrocarbons(PAHs),heterocyclicamines,aromaticamines,and

N-nitrosamines. Each of these carcinogens requires metabolic

activation and detoxification by different enzymatic pathways,

including cytochrome P-450 (CYP), glutathione-S-transferase

(GSTs),and NAD(P)H:quinoneoxidoreductase1 (NQO1).CYP1A1

is a phase I, predominantly extrahepatic, microsomal enzyme

involvedinthebioactivationofPAHs,includingbenzo(a)pyrene.

TwofunctionalCYP1A1polymorphisms areknown; CYP1A1*2A

andCYP1A1*2C.Importantly,bothofthesenormalgeneshavebeen

associatedwithariskforcolorectalcancer[5].

Ever-smokerswereatamoderatelyincreasedriskforincident

colorectalcanceras compared withnever-smokers.Higher risk

estimateswereobservedforcurrentsmokerswithmicrosatellite

instability(MSI)-hightumors,CpGislandmethylatorphenotype

(CIMP)-positivetumors,andBRAFmutation-positivetumors.Other

smoking-relatedvariables(ie,ageatinitiation,totalduration,

aver-agenumberofcigarettessmokedperday,cumulativepack-years,

andinductionperiod)werealsoassociatedwithMSI-high,

CIMP-positive,andBRAFmutation-positivetumorsubtypes[6,7].Global

DNA hypomethylationcan bemeasuredindirectly by assessing

themethylationstatusoflonginterspersednucleotideelement-1

(LINE-1)repeatsequences,andthedegreeofLINE-1

hypomethyl-ationhasbeenrecognizedasanindependentfactorforincreased

cancer-relatedmortalityandoverallmortalityinCRCpatients[8].

Inadditiontosmoking,chronicalcoholconsumptionisarisk

factorforcanceroftheoropharynx,hypopharynx,larynx,

esopha-gus,liver,colorectum,andbreast[9].AccordingtoaWorldCancer

ResearchFund/AmericanInstituteforCancerResearchreview[4],

consumingmorethan30g/dayofethanol fromalcoholicdrinks

placesmalesata“convincing”riskforcolorectalcancerandfemales

ata“probable”riskforthedisease.

There are several possible carcinogenic actions of alcohol,

and one mechanism of action may be through rectal changes.

Alcohol can potentially induce folate deficiency in the colon

and rectumby causing folatemalabsorption or inhibiting

criti-calenzymes.Intestinalbacteriawithhighalcoholdehydrogenase

activityare able tooxidize ethanol in the colon;however, the

activityproducessubstantiallevelsofacetaldehyde[10].Inrats,

concomitantethanoladministrationinaliquiddietpromotes

rec-tal carcinogenesis,which is induced by 1,2-dimethylhydrazine,

10-azoxymethane,andazoxymethylmethylnitrosamine(AMMN).

Since ethanol causesAMMN-inducedrectal carcinogenesis, and

thiseffectdoesnotrequiremetabolicactivation,itispostulatedthat

local,notsystemic,ethanoleffectsmaycontributetocarcinogenic

effectsintherectum[11].

Inaddition,alcoholmaysuppresstumorimmunesurveillance,

affectDNArepair,alterthecompositionofbileacids,orinducethe

expressionoflivercytochromeP-450enzymes,whichmay

conse-quentlyactivateothercarcinogens[12].Lengthofalcoholexposure

isalsoanimportantvariable.Forexample,heavydrinkingcauses

increasedrectalmucosacellproliferation,asshownbyincreased

detectionofdifferentproliferationmarkers,suchasPCNAandKi67.

Inhumans,chronicalcoholabuseleadstorectalmucosal

hyperpro-liferation,aconditionassociatedwithincreasedcancerrisk[13].

Alcohol consumption increases colorectal cancer risk, likely

throughitsanti-folateeffects[14].FolicacidandrelatedB

vita-minsareessentialforDNAmethylation.Severalstudiesindicatea

relationbetweenglobalDNAhypomethylationandchromosomal

instability(CIN)intumorcells[15,16].

Familyhistoryisanindependentriskfactorfordeveloping

colo-rectalcancer.PeoplewithafamilyhistoryofCRCare2.3to4.3times

morelikelytodevelopCRCthanthosewithoutit,dependingonthe

number,relation,andtheageofonsetoftherelative(s)with

can-cer[17].Peoplewhoserelativeshaveearly-onsetCRC(diagnosed

beforeage50)haveahigherriskthanthosewithrelatives

diag-nosedlaterinlife[18].Apotentialmechanismoffamilialclustering

of CRCmaybe heritable predisposition toepigenomic

instabil-ityandthedevelopmentoftumorswithhypomethylationinlong

interspersednucleotideelement1(LINE-1)[19].

Improvingaccesstoappropriate servicesiscrucial to

reduc-ingcolorectalcancermortality,andshouldbegivenpriorityby

alllevelsoftheservice-primarycare,hospitalTrusts,andCancer

Networksinallworld.TheNHSBowelCancerProgram(London,

UK)reduceddeathsfromcolorectalcancer.Thisprogramhasthree

mainstrands:thedevelopmentofanationalscreeningprogram,

streamliningcareforsymptomaticpatients,andimproving

treat-ment.Thiswillbeunderpinnedbyexpansionandmodernization

ofendoscopyservicesandacommunicationsstrategyforpatients

andprofessionals.Researchcenters,universitiesandhospitalshave

played an important role in the implementationof population

screeningforcolorectalcancer,withimprovementsinthe

Euro-peanhealthpopulation[20].

Despitethegrowingresearchinvestigatingtheeffectsof

smok-ing, alcohol, and family history on CRC, data relating to the

prevalenceofthediseaseinnortheastBrazilremainscarce.An

effi-cientscreeningmethodforCRCisstillneededinBrazilinorderto

enhancediagnosisandprognosisofthediseaseforpatients.

Theaimofthisstudywastoidentifytheclinicalandpathological

featuresofCRCfromhospitalrecordsinBrazil.

Methods

Weconductedaretrospectivestudyofallpatientsdiagnosed

withCRCatDr.LuizAntônioHospitalinNatal,RN,Brazil.Between

1995−2005,534casesofcolorectalcancerweredocumentedat

thisHospital.Documentedcaseswerefoundbysearchingfor

colo-rectal cancerin endoscopy reports, and then medical files and

imaging reports werereviewed foreach of thesecases. Patient

records with incomplete information were excluded from the

study,whichleft358CRCdocumentsforanalysis.Weevaluated

numerouspatients’variablesincludingage,sex,historyof

smok-ingoralcoholconsumption,andtherelevantpastorcurrentfamily

history.Inaddition,weusedpathologyreportsandmedicalrecords

toassesstumorlocation,differentiatedtumordifferentiationgrade,

TNMstage,treatmentprotocol,andevolutionofthedisease

follow-ingfiveyearsoftreatment.

Tumorlocationwascategorizedasrightcolonand/orleftcolon.

Rightcolontumorswereoftheappendixextendingtothehepatic

flexureandtransversecolon,whereasleftcolontumorswereofthe

splenicflexureextendingtothesigmoidcolonandrectum.

Treat-mentprotocolswereseparatedintosurgery,radiotherapy(XRT),

and/orchemotherapy(CT).Regardingtheevolutionofthedisease,

datawerecategorizedintoeitheralivinggroup(patientscurrently

freefromdiseaseorintreatment)oradeceasedgroup.

TumorstagingwasbasedontheSeventhEditionoftheAmerican

JointCommitteeonCancer(AJCC)CancerStagingManual.For

anal-ysis,IIIandIVstagewereconsideredHighStageandIandIIstage

wereconsideredLowStage.Intumordifferentiation,thepoorly

differentiatedandundifferentiatedcomponentsweredefinedas

aregioninwhicha cancerhasnoor<50%glandularformation,

irrespectiveofamucin-producingorinvasivepattern.The

well-differentiatedcomponentwasdefinedasaregioninwhichacancer

has>95%glandularformation,andnoinvasivepatternfully

Table1 DescriptiveData.

Variable N % Variable n %

Sex Differentiationgrade

Male 173 48.3 Well 27 7.6 Female 185 51.7 Medium 289 81.9 Race Undifferentiated 37 10.5 White 73 25.9 TNM Mixed 207 73.4 1 28 7.8 Black 2 0.7 2 110 30.7 Alcoholism 3 107 29.9 Yes 130 44.7 4 113 31.6 No 161 55.3 Treatment Smoking Radiotherapy(XRT) 17 4.8 Yes 163 58.2 Chemotherapy(CT) 21 5.9 No 117 41.8 Surgery 33 9.3

Familyhistoryofcolorectalcancer XRT+CT 26 7.3

Yes 63 53.4 XRT+Surgery 35 9.9

No 55 46.6 CT+Surgery 125 35.2

Primarytumorsite XRT+CT+Surgery 98 27.6

Rightcolon 58 17.6 Death

Leftcolon 54 16.4 Yes 106 29.6

Rectum 218 66.1 No 252 70.4

differentiated componentas a >50%glandularformationregion

[21].

Thechi-squareandFisher’sexacttestswereusedforsubgroup

analyses of clinical-pathological features in patients: patients

under50yearsofagewerecomparedwiththoseabove50yearsof

age.Statisticalsignificancewasdeterminedbyapvalueof<0.05.

TheDepartmentalEthicsCommitteeofDr.LuizAntônioHospital

approvedthisproject(024/0030/06).

Results

Atotalof534patientswerediagnosedwithCRCoverthe

10-yearperiodbetween1995−2005.Ofthesepatients,185subjects

wereexcluded due toincomplete data; therefore,358 patients

wereincludedinthisanalysis.Table1presentsdescriptive

meas-uresfromthedata.Theaverageageatdiagnosiswas58.84years

(S.D.=15.26,Med:60years)withaminimumageof15and

max-imumageof101years.Malesrepresented48.3%ofthepatients,

andfemales51.7%.Forty-twopatients(37%)were50yearsofage

oryounger.Themostcommonclinicalpresentationwas

abdom-inalpain(n=77;68%)followedbyrectalbleeding(62%),weight

loss(55%),constipation(50%),melena(14%),andfeverandanemia

(6%).Sixty-fivepatients(53.4%)hadafamilyhistoryofcoloncancer.

OtherdescriptivedataaregiveninTable1.

Similartoalcohol,smokingincreasedthechancefor

develop-ingstageIIIandIVtumors;however,tobaccodidnotsignificantly

interfere withoverall mortality (Table 2). Interestingly, due to

thestrongassociationbetweenalcoholconsumptionandsmoking

(f<0.001;Oddsratio=6.918.95%CI:3.837–12.475),weconducted

afollow-upmultivariateregressionanalysis,whichrevealedthat

onlysmokingwasindependentlyrelatedtohigherstagetumors

(p=0.002.Oddsratio=2.461.95%CI:1.409–4.298).

Discussion

Thisstudyfoundthatthreeindependentriskfactorsinfluenced

CRCoutcomes:smoking,alcoholconsumption,andfamilyhistory.

Specifically,smokingincreasedtheTNMstageofcancertoaIIIand

IVlevel,andbothalcoholconsumptionandfamilyhistoryincreased

theriskfordeathinCRCpatients.

Recentevidencesupportsourfindingthatsmokingisassociated

withCRC.Infact,smokinghistorymaybeaparticularly

impor-tantriskfactorfortheCRCsubtypecharacterizedbymicrosatellite

instability[22],andbyCpGislandmethylatorphenoptype(CIMP)

status andBRAFmutations[23].Smoking-relatedriskmay

per-taintospecificmolecularlydefinedcolorectalcancersubtypesthat

developthroughepigeneticallymediatedcarcinogenicpathways

[6].Therefore,thesedatasuggestthatsmokingmaybeprimarily

associatedwithaCRCsubtypecharacterizedbyapathway

involv-inghyperplastic(serrated) polyps,BRAFmutations,andpositive

CIMPstatus[15].

Colorectalcancerisacomplexdiseaseresultingfromsomatic

genetic and epigenetic alterations, including locus-specific CpG

islandmethylationandglobalDNAorlonginterspersednucleotide

element-1(LINE-1)hypomethylation(b).Theassociationbetween

LINE-1hypomethylationandcoloncancer-specificmortalityhas

Table2 Statisticalresults.

TNM Death

Highstagea_{(%) p OR(IC95%) Yes(%) p OR(IC95%)}

Alcoholism p=0.001 OR:2.22 p=0.034 OR:1.71

Yes 92(70.8) (1.36–3.62) 49(37.7) (1.04–2.82)

No 84(52.2) 42(26.1)

Smoking p<0.001 OR:2.70 p=0.407 –

Yes 115(70.6) (1.65–4.43) 55(33.7)

No 55(47.0) 34(29.1)

Familyhistoryofcolorectalcancer p=0.430 – p=0.002 3.833

Yes 40(63.5) 27(42.9) (1.60–9.16)

No 31(56.4) 9(16.4)

“p”=Chi-squaretest.

notbeenmodified byanyoftheclinicalor molecularvariables

includingsex,age,tumorlocation,stage,andCIMP,microsatellite

instability,KRAS,BRAF,p53,and chromosomalinstabilitystatus.

However, more molecular pathologic epidemiology studies are

neededtoconfirmthisassociationandtoexaminepotential

mecha-nismsbywhichgenome-wideDNAhypomethylationaffectstumor

behavior[8].

Smokinghasbeensignificantlyassociatedwithshorter

disease-freesurvival(DFS)andtimetorecurrence(TTR)inpatientswith

coloncancer. Theseadverse relationshipsweremostevident in

patientswithBRAFwild-typeorKRASmutatedcoloncancer[24].

Epidemiologydatasuggestaprotectiveeffectofsmokingcessation

onaDNAmethylation-relatedcarcinogenesispathwayleadingto

CIMP-highcolorectalcancer[25].

Smokingalsoincreasedthechanceofdevelopingtumorswith

low-gradedifferentiationandhigherTNMstage.Thisfinding

cor-roborateswithcurrentresearchshowingthatsmokingintensity,

particularlybeforeage30,isassociatedwithdecreased

disease-freesurvival.Itisplausiblethenthatgreaterdurationoftobacco

exposuremayleadtoamoreaggressivetumor[26].

Thecurrentdataconfirmedourexpectationthatsmokingand

alcoholconsumptionwerestronglycorrelated,suchthatpatients

whosmokedconsumedmorealcoholthannon-smokers.Despite

thisrelationship,alcoholalonewasassociatedwitha72%increased

risk ofdeath inCRC patients, regardlessof thedegree of

alco-holabuse.Althoughthisisasignificantlylargeincrease,previous

findingssupportourresults.Forexample,priorunivariateand

mul-tivariateanalyses,whichdemonstratedthatalcoholconsumption

wasasignificantandindependentriskfactorforlivermetastasisin

colorectalcarcinomapatients,showedthatneitherthe

consump-tionamountnorthetype ofalcohol influencedlivermetastasis

[27].

Thealcoholmetabolite,acetaldehyde,ishighlytoxic,mutagenic,

and carcinogenic. Acetaldehyde interferes with DNA synthesis

andrepair;consequently,it influencestumordevelopment[28].

Thereareseveralothermechanismsthatmaybeinvolvedinthe

alcohol-associatedcarcinogenicprocess:(1)Localtoxiceffectsof

alcohol,whichleadtomembraneandcellinjuryandsubsequently

cellularproliferation. Hyperproliferation increasessusceptibility

to concomitantly inhaled or ingested carcinogens. Permanent

hyperproliferationis alsoanearlystepin themulti-step

malig-nanttransformationprocess;(2)CytochromeP-4502E1induction,

whichisassociatedwithanincreasedproductionofreactive

oxy-genspeciesandenhancedactivationofavarietyofprocarcinogens,

includingnitrosamines[29].

Directevidencefortheroleofacetylaldehyde(AA)in

alcohol-associatedcarcinogenesisisderivedfromgeneticlinkagestudies

inalcoholics.Polymorphismsand/orgenemutationsthatcodefor

AAgenerationorenzymedetoxificationresultinelevatedAA

con-centrations,whichareassociatedwithincreasedcancerrisks.For

example,40%ofJapanese,KoreanorChineseindividualspossess

theALDH2*2allele.Whenindividualswiththisallelechronically

consumeethanol,theyareatasignificantlyincreasedriskof

devel-opingupperalimentarytractandcolorectalcancer[30].Evenin

studieswithgenotype and phenotypeevaluations,10 common

low-penetrantgeneticvariantshavebeenconsistentlyidentified

throughgenome-wideassociation(GWA)ascontributingtoCRC

risk,mappingto8q24.21(rs6983267),8q23.3(rs16892766),10p14

(rs10795668),11q23.1(rs3802842),15q13.3(rs4779584),18q21

(rs4939827),14q22.2(rs4444235),16q22.1(rs9929218),19q13.1

(rs10411210),and20p12.3 (rs961253)[31].Taken together,the

evidence suggests that there are multiple genetic mechanisms

associatedwithcolorectalcancer.

Currentfindingsofastrongerassociationbetweenlowfolate

andLINE-1hypomethylationaredemonstrated[14].Aspreviously

described,survivalwaspooreramongcoloncancerpatientswith

depleteprediagnosticplasmafolateinourcohorts[15].If

LINE-1hypomethylatedcolontumorsoccurmorefrequentlyinheavy

alcoholdrinkersandfolatedepleteindividuals,thisprovides

com-pelling mechanistic support for the association between folate

depletionandpoorcoloncancersurvival[14].

Inadditiontotheseassociations,theroleoffamilialsyndromes

inCRCdevelopmentis importanttoacknowledge. Forexample,

familialadenomatouspolyposisandLynchsyndromearethemost

frequenthereditaryCRCsyndromes.Thesesyndromesarecaused

by germ line mutations in APC,MUTYH, and mismatch repair

(MMR)genesMLH1,MSH2,MSH6andPMS2,respectively[32].A

familyhistoryofCRCisassociatedwithahighriskofCRCwith

low-level LINE-1methylation,and that geneticpredisposition likely

underliessomaticepigeneticchanges.Itispossiblethatatleasta

subsetofLINE-1methylation-lowCRCmayconstituteapreviously

unrecognizedfamilialcancertrait[33].

Specificgenesaside,familyhistorywasanimportantrisk

fac-torinourstudyfordiseasemortalityinCRCpatients.Ourresults

showedthatthechanceofdyingfromCRCwasalmostthreetimes

greaterinpatientswithafamily historyofcancercomparedto

patientswithoutfamilialcancerassociations.Infact,almost43%of

patientswithafamilyhistoryofCRCdiedcomparedtoonly16.4%

ofsubjectswithoutthis factor.Theliteraturereports conflicting

dataregardingtheinfluenceoffamilyhistoryonCRC.For

exam-ple,anItalianstudyrevealedthatcolorectalcancer-specific5-year

survivalrateswere55.2%and42.5%forhereditarynonpolyposis

colorectalcancer(HNPCC)andnon-hereditarynonpolyposis

colo-rectalcancer(noHNPCC),respectively[34].Therefore,additional

studiesshouldcontinuetoevaluatetheroleoffamilyhistoryin

CRC.

In conclusion, ourdata showed that Brazilian patients with

smoking,alcoholconsumption,and/orafamilyhistoryof

colorec-talcancerweremorelikelytopresentadvancedstageCRCupon

diseasediagnosis.Moreover,theseindividualsweregivenapoor

prognosisregardinghealthandrecovery.Thesedatasuggestthata

massscreeningprograminterconnectedtoMolecularPathologic

Epidemiologyshould beimplemented in northeastern Brazilin

ordertobetterevaluateandaddressthiscommonandpreventable

cancer.ThebestCareCenters(researchandphysicians)inBrazilare

restrictedtotherichestwhocanpayfortheseservices.Theregion

ofnortheasternBrazilstillhashighdeathindexes,causedby

colo-rectalcancerduetolowinvestmentinpreventivediagnosisand

qualificationinpublichealthforthemedicalprofessional(i.e.fill

epidemiologicalvariablesinmedicalrecords).

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