Managing Slow Weight Gain in the Breastfed Infant Assessment & Management Strategies
COMPLEMENTARY FEEDING OF THE BREASTFED CHILD The risk...
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COMPLEMENTARY FEEDING OF THE BREASTFED CHILD The risk of carcinogenic effect Max Mantik
Transcript of COMPLEMENTARY FEEDING OF THE BREASTFED CHILD The risk...
COMPLEMENTARYFEEDINGOFTHEBREASTFEDCHILD
TheriskofcarcinogeniceffectMaxMantik
Objectives
• Todiscusscomplimentarybreastfeeding• Toaddressthelinksbetweenchildhoodenvironmentsandriskonsetofcancer
• Topresentcurrentknowledgeofcausationandenvironmentalriskfactors
• Tobiologicalefects developmentoncancer
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Energyrequired(toplineandtheamountfrombreastmilk)
WHO/UNICEF,1998
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DURATIONOFEXCLUSIVEBREASTFEEDINGANDAGEOFINTRODUCTIONOFCOMPLEMENTARYFOODS
• Exclusivebreastfeedingfrombirthto6monthsofage• Complementaryfoodsat6monthsofage(180days)whilecontinuingtobreastfeed.
• Continuefrequent,on-demandbreastfeedinguntil2yearsofageorbeyond
WHO,guiding principles for complementary feeding of the breastfed child, 2003
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Responsivefeeding
Principlesofpsycho-socialcare• Sensitive• Patiently,andencourage• Combinations,tastes,textures• Minimizedistractions• Periodsoflearningandlove
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SAFEPREPARATIONANDSTORAGEOFCOMPLEMENTARYFOODS• Thepeakincidenceofdiarrhealdiseaseisduringthesecondhalfyearofinfancy,as
• Theintakeofcomplementaryfoodsincreases• Difficulttokeepclean• Feedingbottlesareaparticularlyimportantrouteoftransmissionofpathogens
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SAFEPREPARATIONANDSTORAGEOFCOMPLEMENTARYFOODS
Practicegoodhygieneandproperfoodhandling• Handhygiene• Storingfoodssafelyandservingfoodsimmediately• Cleanutensilstoprepareandservefood• Cleancupsandbowls• Avoidingtheuseoffeedingbottles,whicharedifficulttokeepclean.
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Breastfedchildrenat12-23months
• Indevelopingcountriesabout550g/d• Receive35-40%oftotalenergyneedsfrombreastmilk
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FOODCONSISTENCY
• Graduallyincreasefoodconsistencyandvarietyastheinfantgetsolder
• Pureed,mashedandsemi-solidfoodsbeginningatsixmonths• By8months"fingerfoods"(snacks)• By12months,thesametypesoffoodsasconsumedbytherestofthefamily
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NUTRIENTCONTENTOFCOMPLEMENTARYFOODS
• Varietyoffoodstoensurethatnutrientneedsaremet• Meat,poultry,fishoreggsshouldbeeatendaily,orasoftenaspossible
• VitaminA-richfruitsandvegetablesshouldbeeatendaily• Adequatefatcontent• Avoidgivingdrinkswithlownutrientvalue,suchastea,coffeeandsugarydrinkssuchassoda
• Limittheamountofjuiceofferedsoastoavoiddisplacingmorenutrient-richfoods
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USEOFVITAMIN-MINERALSUPPLEMENTSORFORTIFIEDPRODUCTSFORINFANTANDMOTHER
• Fortifiedcomplementaryfoodsorvitamin-mineralsupplementsfortheinfant,asneeded
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FEEDINGDURINGANDAFTERILLNESS
• Increasefluidintakeduringillness,includingmorefrequentbreastfeeding,andencouragethechildtoeatsoft,varied,appetizing,favoritefoods
• Afterillness,givefoodmoreoftenthanusualandencouragethechildtoeatmore
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Cancersthatdevelopinchildren
• Leukemia 30%• Brainandspinalcordtumors 26%• Neuroblastoma 6%• Wilmstumor 5%• Lymphoma
• Hodgkin 3%• NonHodgkin 5%
• Rhabdomyosarcoma 3% • Retinoblastoma 2%• Bonecancer(includingosteosarcomaandEwingsarcoma) 3%
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RiskFactorsandCausesofChildhoodCancer
• Differentcancershavedifferentriskfactors• Inadults,lifestyle-relatedriskfactors,suchas beingoverweight,eatinganunhealthydiet,notgettingenoughexercise,andhabitslikesmokinganddrinkingalcohol
• Manyyearstoinfluencecancerrisk,andtheyarenotthoughttoplaymuchofaroleinchildhoodcancers
• Radiationexposure,linkwithsometypesofchildhoodcancers• DNAchangesthatturnononcogenes orturnofftumorsuppressorgenes.
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Inheritedversusacquiredgenemutations
• MostchildhoodcancersarenotcausedbyinheritedDNAchanges.TheyaretheresultofDNAchangesthathappenearlyinthechild’slife,sometimesevenbeforebirthà acquiredmutation
• SomechildreninheritDNAchanges(mutations)fromaparentthatincreasetheirriskofcertaintypesofcancer
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Comparedwithadults,infantsandyoungchildren• Eatrelativelymorefoodperunitofbodyweightthandoadults.
• Eatlargequantitiesofsinglefoods.• Playingonthefloorandplacinghandsandobjectsintheirmouths,mayincreaseexposurestopesticides.
• Developingorgansystemssusceptibletotheeffectsofpesticidesorlessabletoclearthemetabolites.
• Uniqueexposurepathwayssuchasthroughtheplacentaandthroughbreastmilk.
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ArtificialSweetener
• CyclamatebannedasfoodadditiveinUSin1969andsaccharinein1977afterbeingassociatedwithbladdercancerinmice
• Underpublicpressure,saccharinereturnedtothemarket;itwasreviewedandtakenoffthelistofpotentialcarcinogensin2000
• Aspartame:noevidenceimplicatingitinincreasedcancerrisk
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Inconsistenciesinresultsofnutritional
• Canbeattributedtomultiplefactors• Observationalstudiesà imprecisionindietrecall• Confoundingfactorsthatinfluencetheriskofcancerandoccurdisproportionatelyamongindividualsexposedandnotexposedtothenutrientofinterest.
• Randomizedcontrolledtrialsà inaccurateresults• pooradherencetothedietaryintervention,• insufficientfollow-uptime,• wrongdoseorformofthenutrient.
• Additionally,studiestendtofocusononenutrientinisolation,when• wholefoodsorthefullcompositionofadietmaycorrelatebetterwithcancerriskthananysinglecomponent.
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Objectives
• Todiscusscomplimentarybreastfeeding• Toaddressthelinksbetweenchildhoodenvironmentsandriskonsetofcancer
• Topresentcurrentknowledgeofcausationandenvironmentalriskfactors
• Tobiologicalefects developmentoncancer
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Cancerinchildren
• Childhoodcancersmakeuplessthan1%ofallcancersdiagnosedeachyear.About10,380childrenintheUnitedStatesundertheageof15willbediagnosedwithcancerin2016.Childhoodcancerrateshavebeenrisingslightlyforthepastfewdecades.
• Becauseofmajortreatmentadvancesinrecentdecades,morethan80%ofchildrenwithcancernowsurvive5yearsormore.Overall,thisisahugeincreasesincethemid-1970s,whenthe5-yearsurvivalratewasabout58%.Still,survivalratesvarydependingonthetypeofcancerandotherfactors.Thesurvivalratesforaspecifictypeofchildhoodcancercanbefoundinourinformationforthatcancertype.
• Afteraccidents,canceristhesecondleadingcauseofdeathinchildrenages1to14.About1,250childrenyoungerthan15yearsoldareexpectedtodiefromcancerin2016.
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HRs (95% CIs) for total cancer and specific cancer types associated with a 1-point increment in WCRF/AICR score (range: 0–6 in men, 0–7 in women).
Dora Romaguera et al. Am J Clin Nutr 2012;96:150-163
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Childhoodexposure
• Children,ingeneral,aremoresusceptibletotoxicants,suchasarsenic,foravarietyofreasonsincluding:moreopportunitiesforexposurefromincreasedhand-to-mouthbehaviorandbreathingclosertotheground,differencesinmetabolism,andgreatersensitivityofthedevelopingnervoussystemtotoxicinsults[101,102].Childrenarelessablethanadultstointernallydetoxifyinorganicarsenicthroughmethylation[101].
• Childrencanbecomepoisonedwitharsenicthroughaccidentalingestion,asinthecaseoftwosiblingswhodrankoutdatedarsenic-containingpesticidestoredinawaterbottle[45].Childrencanalsodeveloparsenicpoisoningfromplayingonsoilcontaminatedwitharsenicfromnearbyminingorsmeltingorinhazardouswastesites.Anotherpotentialsourceofexposureisthroughcontactwith"pressuretreatedwood"throughplayingonit,chewingit,orbeinginthevicinitywhenitisburned
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Cancerprevention
• In2008,therewereanestimated12.7millioncancercasesand7.6millioncancerdeathsworldwide,despiteoverwhelmingevidencethatmanymalignanciesarepreventable[1,2].Survivalratesareimproving,butoverhalfamillionpeoplediefromcancereachyearintheUnitedStatesalone.CanceroutrankscardiovasculardiseaseasthenumberonecauseofdeathintheUnitedStatesforthoseundertheageof85[3].
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• TheInternationalAgencyforResearchonCancer(IARC)hasidentifiedandtabulatedover100humancarcinogens[7].
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Aflatoxins Liver(hepatocellularcarcinoma)
Suppl7(1987);56(1993);82(2002)
Saltedfish,Chinesestyle Nasopharynx Stomach 56(19
Tobaccosmoking Bonemarrow(myeloidleukemia)*;cervix*;oropharynx,hypopharynx);stomach*;ureter*;urinarybladder;insmokers’children:hepatoblastoma*
Breast;insmokers’children:childhoodleukemia(particularlyacutelymphocytic)
38(1986);83(2004)
Benzene Leukemia(acutenonlymphocytic)
Leukemia(acutelymphocytic, chroniclymphocytic,multiplemyeloma,non-Hodgkinlymphoma)
7(1974);29(1982)
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Lifestylefactorshavebeenlinkedtoavarietyofmalignancies• AcomprehensivesystematicreviewwithaglobalfocusconductedbytheWorldCancerResearchFundcametosimilarconclusionsregardingdietary,weight,andactivityfactors[10].
• WorldCancerResearchFund/AmericanInstituteforCancerResearch.Food,Nutrition,PhysicalActivityandthePreventionofCancer:AGlobalPerspective.Washington,DC:AICR,2007
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CanChildhoodCancersBePrevented?
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Screeningforcancerinchildren
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selenium
• Cancer— EpidemiologicstudiessupportapossiblerelationshipbetweenSeandcancermortality[149,150].Asaresult,anumberofstudieshaveinvestigatedtheroleof selenium supplementationforpreventionofcancer.(See "Cancerprevention",sectionon'Selenium' and "Riskfactorsforprostatecancer".)
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Dietary selenium
• Dietaryreferenceintake— isavailablefromseafoods,organmeats,andplantfoods.PlantSecontentdependsuponsoilSeconcentrations.TheRDAforseleniumis20mcgdailyforyoungchildren,risingto55mcgdailyforadults(table2)[23].
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Possiblesignsandsymptomsofcancerinchildren
• Anunusuallumporswelling• Unexplainedpalenessandlossofenergy• Easybruising• Anongoingpaininoneareaofthebody• Limping• Unexplainedfeverorillnessthatdoesn’tgoaway• Frequentheadaches,oftenwithvomiting• Suddeneyeorvisionchanges• Suddenunexplainedweightloss•
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References:CancerinChildren
• AmericanCancerSociety. CancerFacts&Figures2016.Atlanta,Ga:AmericanCancerSociety;2016.
• AmericanCancerSociety. CancerFacts&Figures2014.Atlanta,Ga:AmericanCancerSociety;2014.
• AmericanCancerSociety.Cancersitedetailedguides.Accessedatwww.cancer.org onNovember7,2014.
• Cogliano VJ,BaanR,Straif K,etal.Preventableexposuresassociatedwithhumancancers. JNatlCancerInst.2011;103:1827-1839.
• NationalCancerInstitute.ASnapshotofPediatricCancers.2014.Accessedatwww.cancer.gov/researchandfunding/snapshots/pediatriconNovember7,2014.
• RossJA,SeversonRK,PollockBH,RobisonLL.ChildhoodcancerintheUnitedStates.AgeographicalanalysisofcasesfromthePediatricCooperativeClinicalTrialsgroups. Cancer.1996;77:201-207.
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RiskFactorsandCausesofChildhoodCancer
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Organicallygrownfoods
• arefoodsthataregrownorprocessedwithouttheuseofsyntheticfertilizersorpesticides[1-5].Organicfarmersattempttoprotecttheenvironmentbyusingnaturalmatter(eg,agedmanure,humus,andcompost)forfertilizerandbiologicalmethodsofpestcontrol(eg,croprotationandnaturalinsectpredatorslikeladybugs)[2,4,6].Livestockandpoultryusedforegg,dairy,andmeatproductionareraisedonorganicallygrownfeed,withoutantibioticsorhormones,andprovidedwithaccesstotheoutdoors[6]
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Thestandardsforgrowingandlabelingorganicfood• mayvarydependinguponthecertifyingorganizationoragency.TheWorldHealthOrganization(WHO)andtheFoodandAgricultureOrganization[7],aswellastheEnvironmentalProtectionAgency(EPA)oftheUnitedStateshaveadoptedorproposedguidelinesfortheproduction,processing,labeling,andmarketingoforganicfoodsinanattempttoensurethatallfoodsthatarelabeledorganicmeetthesameminimumstandards.
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Labelingrequirements
• —AsofApril,2008,foodthatislabeled"100percentorganic"or"organic"intheUnitedStatesmustmeetthestandardsoftheUnitedStatesDepartmentofAgriculture(USDA),withthefollowinglabelingrequirements[8]:
• ●Tobelabeledas"100percentorganic,"allingredientsmustbecertifiedasorganicallyproducedandprocessed(excludingwaterandsalt).
• ●Tobelabeled"organic,"foodsmustconsistofatleast95percentcertifiedorganicallyprocessedingredients(excludingwaterandsalt);theremaining5percentofingredientsmaybenon-organicallyproducedbutmustbeontheUSDA'sNationalList.
• ●Productsatleast70percentcertifiedorganicingredients(excludingwaterandsalt)canusetheclaim"madewithorganicingredients"andmaylistuptothreeindividualorganicallyproducedingredientsonthesidepanel,butmaynotclaimtobeorganiconthefrontofthepackage.
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Exposureinchildhood
• Mostevidenceindicatesthattracesofpesticideresiduesinfoodsarenotaproblemformostpeople[83].However,dataarelimitedregardingthetoxicologic consequencesofexposuretopesticideresidueduringinfancyandearlychildhood[84].
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TheFDAmonitorsnutritionalconcerns
• ,includingpesticideexposure,throughtheTotalDietStudy.Thisstudyexamines234foodsselectedtotypifytheAmericandiet.Between1985and1991,analysisofthesefoodsrevealed:
• ●Noresidueswerefoundininfantformulas• ●NoresiduesovertheEPAtoleranceorFDAactionlevelwerefoundinanyofthe"marketbasket"foods
• ●Lowlevelsof malathion werefoundinsomecereals• ●Lowlevelsofthiabendazole,apost-harvestfungicide,werefoundonsomefruitsandfruitproducts
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Factorstoconsiderwhendecidingwhethertouseorganicproductsinclude:
• •Organicfoodsarenotfreeofsyntheticpesticide residues,buttypicallycontainsmalleramountsthanarepresentonconventionallygrownfoods.Thus,organicallygrownfoodsprovideanalternative sourceoffruitsandvegetablesforindividualswhoareconcernedaboutsyntheticpesticides.(See 'Reductionofexposure' above.)
• •Infantsandchildrenmaybemoresusceptibletotheadverseeffects ofpesticidesthanareadults.(See 'Exposureinutero' aboveand 'Exposureinchildhood' above.)
• •Ingeneral,thetracesofpesticideresiduethatarefoundinfoodposelittlethreattohumanhealth. Potentialadverseeffects ofpesticideexposureonspecialpopulationsincludeneurologic,developmental,andreproductivedisorders.(See 'Exposureinutero' aboveand 'Adverseeffects' above.)
• •Populationsinvolvedinagriculturalworkhavehigherlevelsofpesticide exposure,butevidence ofadverseeffectsofsuchexposurelevels islimited.(See 'Exposureinutero' aboveand 'Exposureinchildhood' above.)
• •Pesticides helptomaintainanabundantandvariedfoodsupply.Pesticide useisregulatedbytheEPAandenforcedbytheUSDAandtheFDA.Effortsarebeingmadetoensurethattheseregulationsareappropriateforinfantsandchildren.(See 'Pesticideregulation' above.)
• •Exposuretopesticide residueineitherorganicorconventionallygrownfoodcanbereducedthroughwashing,peeling,cooking,orprocessingoffoods.(See 'Reductionofexposure' above.)
• •Organicfoodproductiondoesnoteliminate theriskoffoodborneillness,and"organic"shouldnotbeinterpretedasmeaning "safe".(See 'Microbialinfection' above.)
• •Organicfarmingistypicallyperformedbysmaller,family-ownedfarmsandmaybemoreenvironmentallyfriendly[5].
• •Because organicfarmingprohibitsnontherapeuticantibiotics, itmayreducetheriskofdiseaseattributedtoorganismsthat areresistanttomultipleantibiotics.(See 'Hormone,sex-steroid,andantibiotictreatment oflivestock' above.)
• •Ithasbeenpostulatedthat ingestedestrogeninfoodderivedfromsex-hormone-treatedanimalsmayleadtoearlierdevelopment ofpuberty,butlimitedstudieshavenotsupportedthishypothesisinhumans.(See 'Hormone,sex-steroid,andantibiotictreatment oflivestock' above.)
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reduceexposuretofoodbornepathogensandpesticides:
• •Buythefreshestfoodsavailable.Theywillhavethebesttasteandhighestnutrient (ie,vitamin)content.• •Considerusingfrozenorcannedfruitsandvegetablesasanalternativeorsupplement tofreshproduce.Thesefoodsmaintainmostoftheirnutritionalvalueandmayalsoreducepesticideexposureascomparedtofreshproduce.
• •Eatavarietyoffoods toensureabalancednutritional intakeandtolessencontaminationfromanyonesource.
• •Selectproduce thatisfreeofdirt,insectholes,mold,ordecay.(See 'Naturaltoxins' above.)• •Alwayswashfruitsandvegetablesthoroughly withadishbrush,butdonotusesoaporotherdetergents.• •Peelfruitsandvegetablesbeforeeatingandthrowawaytheouterleavesof leafyvegetables.Somenutrientsandfibermaybelostwhenproduce ispeeled.
• •Trimfatfrommeatandskinfrompoultryandfishbecausesomepesticideresiduesareconcentratedinfat.• •Makesurethatapplejuiceandciderarepasteurized, toreducetheriskoffood-borne illnesssuchasE.ColiO157.(See 'Microbialinfection' above.)
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Arsenicexposureisassociatedwithcancers
• ●Skincancer– Ingestionofinorganicarsenicincreasestheriskofdeveloping skincancers(picture1)[69].Lesionscommonlydescribedaremultiple squamouscellcarcinomas,arisingfromthearsenichyperkeratoticwarts,aswellasbasalcellcarcinomasarisingfromcellsnotassociatedwithhyperkeratinization.
• ●Bladdercancer– Therehasalsobeenconsiderableepidemiologic evidencetosupport theassociationbetweenexposuretoinorganicarsenicandbladdercancer[67].AcohortstudyfromTaiwanfound that,comparedwithpeopledrinking waterwithanarsenicconcentrationof≤10 mcg/L, theadjustedrelativerisksofbladdercancerinpeopleexposedtowellwatercontainingarsenicinconcentrationsof10.1to50,50.1to100,and>100 mcg/L were1.9,8.2,and15.3,respectively[70].(See "Epidemiology andriskfactorsofurothelial (transitionalcell)carcinomaofthebladder", sectionon'Drinkingwater'.)
• ●Lungcancer– Thereisevidencetosupport anassociationbetweenarsenicexposureandlungcancer[67,71-73].ObservationalstudiesfromChilehavefound adose-response relationship,withevidencethattheriskforlungcancermaybegintoincreasewhenarsenicconcentrationsindrinkingwaterreachapproximately60 mcg/L [71,72].Theadjustedrelativeriskfor lungcancerwas8.9fordrinking waterwitharsenicconcentrationsof200to400 mcg/L [72].Inanother study,mortalityratesfromlungcancerdeclinedfollowing theeliminationofarsenicfromdrinkingwater[74].Thereisalsoevidenceof synergybetweenarsenicandsmokingontheriskoflungcancer[72,73].(See "Cigarettesmokingandotherpossible riskfactorsforlungcancer",sectionon'Occupationalandenvironmental carcinogens'.)
• ●Liver – Arsenicexposureisbelievedtoincreasetheriskofhepaticangiosarcomas,butitdoesnotappeartobeassociatedwithhepatocellularcarcinoma[75].
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N-nitroso compounds
• N-nitroso compoundsarepotentneurocarcinogens inanimalmodels[59].Humanexposuretotheseagentsoccursfrombothendogenousandexogenoussources.
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N-nitroso compounds
• Exogenous– ThemajorexogenoussourcesofpopulationexposurestoN-nitroso compoundsincludetobaccosmoke,cosmetics,automobileinteriors,andcuredmeats[11].Othersourcesincluderubberproducts(babypacifiers,bottlenipples)andcertaindrugsincludingantihistamines,diuretics,oralhypoglycemicagents,antibiotics,tranquilizers,andopiates.N-nitrodiethanolamine,acarcinogeninanimalmodels,occursmainlyasacontaminantincosmeticproducts,soaps,shampoos,andhandlotions.
• ●Endogenous– EndogenousformationofN-nitroso compoundsisacomplexprocessthatoccursinthestomach,andisdependentuponthepresenceofNOCprecursors,gastricpH,thepresenceofbacteria,andotherphysiologicparameters[3].Thus,measurementofexposuretoendogenousNOCsisextremelydifficult.
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• Inthefourlargestcase-controlstudies,allofwhichincludedover200patientsdiagnosedwithgliomaandappropriatecontrols,andsomeassessmentofmeatintake[60-63],tworeportedasignificanttwo- tothreefoldincreasedriskofgliomaforhighconsumersofcuredmeatorbacon,ascomparedwiththosewithalowintake[61,62].However,excessriskswereonlyobservedamongmenand,inone,therelativeriskswereforhighintakeofcuredmeatincombinationwithlowfruitandvegetableintake[61].Ameta-analysisthatincludednineobservationalstudies(primarilycase-controlstudies)reportedarelativeriskof1.48(95%CI1.20-1.83)foradultgliomaamongindividualswithahighintakeofcuredmeat[64].
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• TwomorerecentpublicationsusingdatafromprospectivecohortstudiesfoundnoassociationswithmeatintakeordietaryN-nitrosocompounds[65,66].Bothstudieshadover300gliomacasesanddetaileddietaryassessmenttoexaminetheseexposuresandtheirpotentialrelationtogliomarisk.ThelackofassociationinthesetwolargeprospectivestudiescastdoubtontheN-nitroso compoundhypothesis,atleastinrelationtoadultgliomarisk.
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Antioxidants,fruits,andvegetables
• — IndirectsupportfortheNOChypothesisincludestheobservationthatcertaininhibitorsofthenitrosation process,vitaminsCandE,appeartoreducebraintumorriskinadultsandchildren[11,46,67].Dietarystudieshavedemonstratedareducedriskofbraintumorsinchildrenwhoconsumeincreasedamountsoffruitsandfruitjuices[11].Prenatalvitaminsupplementation(includingvitaminsAandCandfolate)andincreasedmaternalintakeofvegetableshavebeenassociatedwithaloweredbraintumorriskintheoffspring[67-69].
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dietarytraceminerals
• Cancer— EpidemiologicstudiessupportapossiblerelationshipbetweenSeandcancermortality[149,150].Asaresult,anumberofstudieshaveinvestigatedtheroleof selenium supplementationforpreventionofcancer.(See "Cancerprevention",sectionon'Selenium' and "Riskfactorsforprostatecancer".)
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Selenium
• — Animalstudiessuggestthat seleniumdecreasestheriskofavarietyoftumors,andsomeepidemiologicstudieshaveshownaninverserelationshipbetweenseleniumandcancer[148-150].OnestudyusingNHANESIIIdatafrom14,000adultsfoundaninverseassociationbetweenseleniumlevelsandcancermortalityatlevelsofseleniumupto130 ng/mL butanincreaseinmortalityatlevels>150 ng/mL [151].
• Aplacebo-controlledrandomizedtrialof selenium forpreventionofnonmelanoma skincancershowedasignificantmortalityreductionincancersofthelung,colon,andprostate[152].Asystematicreviewoftheeffectsofantioxidantsupplementsoncancerincludedfourrandomizedtrialsofseleniumaloneorincombinationwithothersupplementsandfoundthatseleniumreducedtheoverallriskofcancerinmen(RR0.77,95%CI0.64-0.92)butnotinwomen[153].However,alatermeta-analysisofrandomizedtrialsofantioxidanttherapyincludedfivetrialsofseleniumandfoundnosignificantcancerriskreduction(RR0.62,0.36-1.08)[154].
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Dietaryfat
• Dietaryfathasbeenextensivelystudiedasapossiblefactorexplainingthevariationininternationalcancerrates.Noclearlinkhasbeenfoundbetweentotalfatintakeandcolonorbreastcancer;thedataaresomewhatmoreconvincingforprostatecancer
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Redmeat
• —Highintakeofredmeathasbeenassociatedwithincreasedriskofcoloncancer.AworkinggroupoftheInternationalAgencyforResearchonCancer(IARC)reviewedobservationalstudiesevaluatingtheassociationofcancerwithredmeatorprocessedmeatconsumption,givingthehighestweighttoprospectivecohortstudiesandpopulation-basedcase-controlstudies[63].Thelargestbodyofevidencerelatedtoassociationswithcolorectalcancer,with7of14cohortstudiesand7of15casecontrolstudiesfindingpositiveassociationsforredmeatandcolorectalcancer,and12of18cohortstudiesand6of9case-controlstudiesfindinganassociationforprocessedmeatandcolorectalcancer.Ameta-analysisfoundadose-responserelationshipbasedon10cohortstudies,withriskincreasedby17percent(CI1.05-1.31)per100 g/day ofredmeatandincreasedby18percent(95%CI1.1-1.28)per50 g/day ofprocessedmeat.Theworkinggroupconcludedthatevidencewassufficienttoidentifycarcinogenicityforprocessedmeatbutlimitedfortheassociationofredmeatconsumptionandcancer
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Fruitsandvegetables
• — Despitesuggestionsfromcase-controlstudiesthathighintakeoffruitandvegetablesisassociatedwithasignificantreductionincancer,prospectivestudieshavefoundlessconsistentresults[66-69].DatafromtheEuropeanProspectiveInvestigationintoCancerandNutrition(EPIC)study,acohortstudyofnearly500,000Europeanmenandwomenfollowedfornineyears,foundonlyaweakassociationbetweenincreasedintakeoffruitsandvegetableswithoverallriskofcancer(HR0.97,95%CI0.96-0.99)[70].
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• Ameta-analysisfoundthatintakeofhighamountsofsoy(20 mg/day ofisoflavone)inAsianwomenwasassociatedwithadecreasedriskforbreastcancercomparedwithAsianwomenconsumingloweramounts(5 mg/day) [79].However,eventhelowestintakeofsoyisoflavones intheAsianpopulationwasmorethanfivefoldthe"high"intake(0.8 mg/day) ofwomeninWesterncountries,wherestudieshavenotshownaprotectiveeffectforsoy.Inanothermeta-analysis,Chinesewomenwhowereinthehighestquintileofsoyintakehadadecreasedriskoflungcancercomparedwiththoseinthelowestquintile[80].Increasedflavonoidsfoundintomatoes,greenpeppers,berries,andcitrusfruitshavebeenassociatedwithamodestdecreaseinbreastcancerriskinWesternpopulations[81].
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Dairy
• — Therelationshipbetweendairyintakeandovariancancerisuncertain.Twometa-analysesevaluatingtherelationshipofdairyfoodintakeandovariancancerfoundnoevidenceofasignificantassociation[82,83],whileathirdmeta-analysisof21studiesfoundnoassociationincase-controlstudies(RR0.96),butthreeprospectivecohortstudiesdiddemonstrateincreasedriskofovariancancerwithhighintakeofdairyfoods(RR1.13,95%CI1.05-1.22)[84].Inaccuracyofretrospectivedietreportsinthecase-controlstudiesmayaffecttheirreliability[85].However,asubsequentcohortstudyfoundnoincreaseinriskofovariancancerwithdietarydairyorlactoseintake[86].Thus,therelationshipofdairyintaketoovariancancerisuncertain
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Fiber
• — Fiberintakeisassociatedwithareductionintheriskofheartdisease[93,94]anddiabetes[95,96],butitseffectoncancerriskreductionislesscertain.Resultshavebeenvariableamonglargeepidemiologicstudiesandmeta-analyses,andthedegreeofprotectionfromdietaryfiber,ifany,willremainunsettleduntilprospectiveinterventionstudiesaredone.Intheabsenceofrandomizedtrials,observationaldatamaybeconfoundedbytherelationshipoffiberintakewithothermicronutrientsandwithotherchoicesrelatedtolifestyleanddiet.(See "Colorectalcancer:Epidemiology,riskfactors,andprotectivefactors",sectionon'Fiber'.)
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Fiber
• Severallargeepidemiologicstudieshavereportedasignificantinverseassociatedbetweenfiberintakeandcolorectalcancerrisk.Asanexample,alargeEuropeanstudyinvolving519,978patientsfoundthatintakeofdietaryfiberwasinverselyrelatedtocoloncancerincidence(adjustedRR0.58,95%CI0.41-0.85),comparingthehighesttolowestquintilesoffiberintake[97].However,theresultsmayhavebeenconfoundedbylackofcontrolforfolateintake,andfibermayhaveservedasaproxyforthismicronutrient.(See 'FolateandotherBvitamins' below.)
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Omega-3fattyacidsanddietaryfish
• — Asystematicreviewofprospectivestudiesevaluatingtheeffectofomega-3fattyacidconsumptionontumorincidenceconcludedthatthereisnoassociationbetweenomega-3fattyacidsandcancerriskfor11differenttypesofcancer[119].Tenstudiesevaluatedinthisreviewreportedsignificantfindings,butindividualstudiesindicatedbothincreasedanddecreasedriskwithnoconsistentpattern.Asubsequentrandomizedtrialfoundanincreaseincancerriskforwomentreatedwithomega-3fattyacids,butnotformen[120].
• Whileanassociationhasnotbeenfoundfordietarysupplementationwithomega-3fattyacidsandcancerincidence,anassociationwasfoundinasystematicreviewof41observationalstudiesforfishconsumptionandadecreasedincidenceofcolorectalcancer[121].Inthatanalysis,includingcase-controlandcohortstudies,aninverserelationshipbetweenfishintakeandrectalcancerwasdemonstrated(oddsratio[OR]0.79,95%CI0.65-0.97),whileaninversetrendwassuggestedforcoloncancer(OR0.96,95%CI0.81-1.14).
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VITAMINSANDMICRONUTRIENTS
• — Multipleobservationalandprospectivestudiesoftheuseofsupplementalvitaminsandmineralstopreventcancerhavebeendisappointing[122].Asystematicreviewof38studiesfoundthatneither vitaminC nor vitaminE supplementationwasbeneficialforpreventionofthecancersevaluated[123].A2006NationalInstitutesofHealth(NIH)consensusconferencepanelconcludedthat"presentevidenceisinsufficienttorecommendeitherfororagainsttheuseofmultivitaminsupplementsbytheAmericanpublictopreventchronicdisease"[124].Asubsequentlong-termrandomizedtrial(mean9.4yearstreatment)in8000womenfoundnoevidencethatsupplementationwithvitaminC,E,or beta-carotene (singlyorincombination)decreasedcancerincidenceorcancermortality[125].Additionally,twolong-termobservationalstudies,oneincludingover160,000womenwithfollow-upofapproximatelyeightyears[126]andanotherincludingover180,000multiethnicparticipantswith11-yearfollow-up[127],foundnoassociationbetweenmultivitaminuseandriskofcancer.(See "Vitaminsupplementationindiseaseprevention".)
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SeleniumandVit E
• Basedonpreliminaryevidencefromearliersmallertrials,theroleof selenium indecreasingtheincidenceofprostatecancerwasevaluatedinthemuchlargerSeleniumand VitaminE CancerPreventionTrial(SELECT),whichincludedover35,000men[155].ThetrialwasstoppedprematurelyforfutilityasneithervitaminEnorseleniumprotectedparticipantsfromprostatecancerandtherewasanonsignificanttrendtowardincreasedriskfordiabetesintheseleniumgroup[156].(See "Chemopreventionstrategiesinprostatecancer",sectionon'Selenium' and "Riskfactorsfortype2diabetesmellitus",sectionon'Selenium'.)
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VitaminE
• — Evidencedoesnotsupportarolefor vitaminE supplementationinthepreventionofcancer,andsomeevidencesuggeststhatvitaminEmaybeharmful.In2014,theUSPSTFmadearecommendationagainstuseofvitaminEforcancerprevention,citingadequateevidenceoflackofbenefit,butalsonotedadequateevidencethatvitaminEhasfewornosubstantialharms[132].
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• Inlong-termfollow-up(7upto12years)oftheSELECTtrial,theriskofprostatecancerwashigherinthemenwhowereassignedtotake vitaminE alonecomparedwithplacebo(HR1.17,99%CI1.004-1.36)[157].
• ●VitaminE (600internationalunitsofalpha-tocopheroleveryotherday)didnotpreventinvasivecancerina10-yearfollow-uptotheWomen'sHealthStudy,evaluatinghealthywomenage45yearsandolder(meanage55years)[158].NeithervitaminEnor vitaminC decreasedriskforprostateortotalcancerinaPhysicians'HealthStudyrandomizedtrialof14,641menaged50andolderfollowedforeightyears[159].
• ●Inameta-analysisofsixrandomizedtrials, vitaminE supplementationhadnoeffectoncancerincidenceorcancermortality[153].
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DIETPATTERNS
• —Dietarypatterns,insteadofcomponentsofthedietinisolation,havebeenthefocusofanexpandingbodyofliterature.
• TheMediterraneandietischaracterizedbyahighintakeoffruits,vegetables,nuts,legumes,wholewheatbread,fish,andoliveoil.AlargecohortstudyinGreecefoundthat,whencompliancewiththeMediterraneandietwasscoredona10-pointscale,atwo-pointincreaseinadherencetothetraditionalGreekMediterraneandietwasassociatedwitha12percentlowerriskofcancer[186].InalargeranalysisoftheEPICcohort,greateradherencetotheMediterraneandietalsowasassociatedwithadecreasedriskofcancer(foreverytwo-pointincreaseindietscore,cancerriskdecreased4percent),withasuggestionofastrongerassociationwithsmoking-relatedcancers[187].
• TheMediterraneandiethasnotconsistentlybeenassociatedwithdecreasedriskofanyspecifictumor.AdecreasedriskofcolorectalcancerwasidentifiedinonelargecohortstudyinEurope[188],butnotinalargeUnitedStatescohort[189].DataforbreastcancerissimilarlymixedwithnoassociationfoundamongSwedishandBritishcohorts[190,191],whiledatafromtheEuropeanProspectiveInvestigationintoCancerandNutrition(EPIC)cohortidentifiedanassociationforoverallbreastcancerriskandriskofpostmenopausaltumors[192].Theassociationwasmorepronouncedfor estrogen-receptor-negative/progesterone-receptor-negative (ER-/PR-) tumors.
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DIET
• — Avarietyofdietaryfactorshavebeenstudiedinrelationtocancer.Overall,dietaryfat,fruits,vegetables,andfiberhavenotconsistentlybeenshowntoaffectcancerrisk[56].Intakeofothernutrients,particularlycertainmicronutrients,mayofferadegreeofprotectionagainstcertainmalignancies
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Fruitandvegetablesandcancerrisk
• Currentadviceinrelationtodietandcancershouldincludetherecommendationtoconsumeadequateamountsoffruitandvegetables,butshouldputmostemphasisonthewell-establishedadverseeffectsofobesityandhighalcoholintakes
• KeyTJ,BrJCancer.2011
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