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RESEARCHARTICLEOpenAccessTP53geneticpolymorphisms,interactionswithlifestylefactorsandlungcancerrisk:acasecontrolstudyinaChinesepopulationYanliLi1,Shen-ChihChang2,RunguiNiu3,LiLiu4,ChristinaRCrabtree-Ide1,BaoxingZhao4,JianpingShi4,XiaoyouHan3,JiaweiLi5,JiaSu5,LinCai6,ShunzhangYu5,Zuo-FengZhang2andLinaMu1*AbstractBackground:Apathway-basedgenotypinganalysissuggestedrs2078486wasanovelTP53SNP,butveryfewstudiesreplicatethisassociation.
TP53rs1042522isthemostcommonlystudiedSNP,butveryfewstudiesexamineditspotentialinteractionwithenvironmentalfactorsinrelationtolungcancerrisk.
ThisstudyaimstoexamineassociationsbetweentwoTP53single-nucleotidepolymorphisms(SNPs)(rs2078486,rs1042522),theirpotentialinteractionwithenvironmentalfactorsandriskoflungcancer.
Methods:Acase–controlstudywasconductedinTaiyuan,China.
Unconditionallogisticregressionwasusedtoestimateoddsratios(ORs)and95%confidenceintervals(95%CIs).
MultiplicativeandadditiveinteractionsbetweenTP53SNPsandlifestylefactorswereevaluated.
Results:VariantTP53rs2078486SNPwassignificantlyassociatedwithelevatedlungcancerriskamongsmokers(OR:1.
70,95%CI:1.
08-2.
67)andindividualswithhighindoorairpollutionexposure(OR:1.
51,95%CI:1.
00-2.
30).
SignificantorborderlinesignificantmultiplicativeandadditiveinteractionswerefoundbetweenTP53rs2078486polymorphismwithsmokingandindoorairpollutionexposure.
ThevariantgenotypeofTP53SNPrs1042522significantlyincreasedlungcancerriskinthetotalpopulation(OR:1.
57,95%CI:1.
11-2.
21),buttherewasnoevidenceofheterogeneityamongindividualswithdifferentlifestylefactors.
Conclusions:ThisstudyconfirmedthatTP53rs2078486SNPispotentiallyanovelTP53SNPthatmayaffectlungcancerrisk.
OurstudyalsosuggestedpotentialsynergeticeffectsofTP53rs2078486SNPwithsmokingandindoorairpollutionexposureonlungcancerrisk.
Keywords:Lungcancer,TP53,Single-nucleotidepolymorphism,ChinesepopulationBackgroundLungcancerisoneofthemostcommoncancersandisaleadingcauseofcancerdeathinChina.
Itwasesti-matedthatbyyear2025,morethanonemillionChinesewillbediagnosedwithlungcancerperyear[1].
Lungcancermortalityincreased465%duringthepast30yearsandnowistheleadingcancerdeathcauseinChina[2].
Smokingisregardedasthemostimportantriskfactorforlungcancer,andindoorairpollutionfromcookingandheatingisanotherpotentialriskfactorinChinesepopulation[3].
However,approximatelyoneintenlife-timesmokersdeveloplungcancer,whichimpliesapos-sibleroleforgeneticsusceptibilityinthedevelopmentoflungcancer[4].
TheTP53tumorsuppressorgeneplaysacriticalroleinmodulatingtranscriptionofgenesthatgovernthemajordefensesagainsttumorgrowth,includingcellcyclearrest,apoptosis,maintenanceofgeneticintegrity,inhibitionofangiogenesisandcellularsenescence[5].
TheTP53geneharborshigh-frequency,functionalsingle-nucleotidepolymorphisms(SNPs)whichmayalterP53proteinfunction[6].
SeveralfunctionalTP53SNPshavebeenreportedtobeassociatedwithrisk*Correspondence:linamu@buffalo.
eduEqualcontributors1DepartmentofSocialandPreventiveMedicine,SchoolofPublicHealthandHealthProfessions,TheStateUniversityofNewYork(SUNY)atBuffalo,273AFarberHall,Buffalo,NewYork14214-8001,USAFulllistofauthorinformationisavailableattheendofthearticle2013Lietal.
;licenseeBioMedCentralLtd.
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(http://creativecommons.
org/licenses/by/2.
0),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Lietal.
BMCCancer2013,13:607http://www.
biomedcentral.
com/1471-2407/13/607ofdevelopingdifferenthumancancers,includinglungcancer[7-9].
TP53rs2078486SNPwasrecentlyidentifiedtobeas-sociatedwithlungcancerriskinlifetimeneversmokersinapathway-basedgenotypingstudywhichevaluatedacomprehensivepanelof11,737SNPsininflammatory-pathwaygenes[10].
Onecase–controlstudyconductedamong611lungcancercasesand1040controlsinLosAngelesfoundelevatedlungcancerriskassociatedwiththevariantgenotypeofTP53rs2078486SNP(doctoraldissertationfromYiRenWang)[11].
Howeverthisasso-ciationwasnotconfirmedbyanotherpooledgenome-wideassociationstudy[12].
Inadditiontolungcancer,TP53rs2078486SNPhasbeenalsolinkedwithriskofovariancancer[13]andschizophrenia[14].
Toourknowledge,nocase–controlstudyhasbeenconductedintheAsianpopulationtoreplicatetheassociationofTP53rs2078486SNPwithlungcancer.
ThemoststudiedTP53SNPrs1042522ischaracter-izedbysubstitutionofArginine(Arg)byProline(Pro)atcodon72(G12139C,Arg72Pro)andmaynoticeablyaffectP53function[15].
However,veryfewstudiesex-aminedifthereareinteractionsbetweenArg72Propoly-morphismandsmokingorotherlifestylefactorsonlungcancerrisk.
Acase–controlstudywasconductedtoexaminetheassociationsofTP53rs2078486andrs1042522SNPswithlungcancerriskinaChinesepopulationandfur-therexploretheirinteractionswithsomedemographicandlifestylefactors.
MethodsStudyparticipantsAcase–controlstudywasconductedbetween2005and2007inTaiyuancity,thecapitalofShanxiprovince,China.
Theoriginalstudypopulationhasbeendescribedindetailpreviously[16].
Priortotheinitiationoftherecruitment,IRBapprovalswereobtainedfromFudanUniversity(IRB#04-10-0022)andUCLA(IRB#11-003153),respectively.
LungcancercaseswereenrolledfromtheShanxitumorhospital,whichadmittedabout70%ofthecancerpatientsfromthecity.
Eligiblecaseswerenewlydiagnosedlungcancercases,20yearsofageorolder,livedinTaiyuancityfor10yearsormore,instablemed-icalconditionandwillingtoparticipate.
Controlswererandomlyselectedfrom13communitiesinTaiyuancity.
Eligiblecontrolswere20yearsofageorolder,musthavelivedinTaiyuancityfor10yearsormore,andhadnohistoryofcanceroranyotherseriouschronicdiseases.
Atotalof399lungcancerpatientsand466healthycontrolswererecruitedtoparticipateinthisstudy.
Responserateswere89%foreligiblecasesand85%foreligiblecontrols.
Writteninformedconsentwasobtainedfromallstudyparticipants.
DatacollectionAllcasesandcontrolswereinterviewedbyprofessionalstafftocollectinformationondemographicfactors,diet-aryandcookinghabits,activeandpassivesmokinghistory,alcoholdrinkinghabits,teadrinkinghabits,residenceandhousinghistory,occupationalhistoryandrelatedexpos-ure,physicalactivitiesanddiseasehistory.
BloodsamplecollectionandlaboratoryanalysisofgenepolymorphismsBloodsampleswerecollectedfrom97.
9%ofcasesand98.
9%ofcontrols.
Serumandbloodclotwereimmediatelyseparatedandallsampleswerestoredinfreezerat80°C.
GenomicDNAwasextractedusingamodifiedphenol-chloroformprotocol.
GenotypingwasperformedintheMolecularEpidemiologyLaboratoryatDepartmentofEpidemiology,SchoolofPublicHealthatUCLA.
TP53SNPgenotypingwasperformedusingSequenomplatform(Sequenom,Inc.
,SanDiego,CA).
Polymerasechainreac-tion(PCR)andextensionprimersweredesignedusingMassARRAYAssayDesign3.
1software(Sequenom,Inc.
,SanDiego,CA).
Genotypingprocedureswereperformedaccordingtothemanufacturer'siPLEXApplicationGuide(SequenomInc.
SanDiego,CA).
Forqualitycontrol,weincludedtwonegativecontrols(H2O)ineach96-wellplate.
Around4.
5%ofsampleswereselectedfordupli-cationandtheconcordanceis99.
5%.
Wefoundnoob-viousdeviationsfromHardy-WeinbergequilibriumforbothSNPs(rs2078486:χ2=0.
19,P=0.
6629;rs1042522:χ2=4.
24,P=0.
0395)amongcontrolsubjects.
WedidnotfindstronglinkagedisequilibriumbetweenthetwoSNPs(D'65yrs133(33.
3)128(27.
4)GenderMale202(50.
6)234(50.
2)0.
9038Female197(49.
4)232(49.
8)EducationIlliterate43(10.
8)23(4.
9)<.
0001Primaryschool106(26.
6)81(17.
4)Juniormiddleschool124(31.
1)175(37.
5)Seniormiddleschool68(17.
0)120(25.
8)Collegeorhigher58(14.
5)67(14.
4)PackyearsofsmokingNonsmokers179(44.
9)285(61.
2)<.
0001<20pyrs39(9.
8)62(13.
3)20–40pyrs64(16.
0)72(15.
5)≥40pyrs117(29.
3)47(10.
1)Averageincome10yearsago<1,000yuan104(26.
1)106(22.
7)<.
00011,000–2,500yuan236(59.
1)197(42.
3)≥2,500yuan59(14.
8)163(35.
0)BMI(kg/m2)<18.
522(5.
8)9(2.
0)<.
000118.
5–24.
9250(66.
3)259(56.
3)25–29.
990(23.
9)162(35.
2)≥3015(4.
0)30(6.
5)AlcoholdrinkingNo298(74.
7)345(74.
0)0.
8267Yes101(25.
3)121(26.
0)TeadrinkingNo242(60.
6)263(56.
5)<.
0001Previousdrinkers47(11.
8)15(3.
2)Currentdrinkers110(27.
6)188(40.
3)Total399466Adjustedage,gender,education,packyearsofsmoking,alcoholdrinking,teadrinkingandaverageincome10yearsago.
Significantdifferenceswerehighlightedinbold.
Lietal.
BMCCancer2013,13:607Page3of9http://www.
biomedcentral.
com/1471-2407/13/607Table2AssociationsofTP53SNPswithlungcancerriskinTaiyuanlungcancerstudyintotalstudypopulationSNPGenotypeCasesControlsCrudeOR(95%CI)AdjustedOR*(95%CI)N%N%TP53rs2078486355448CC18652.
425055.
811TC13638.
316737.
31.
10(0.
82,1.
47)1.
20(0.
88,1.
64)TT339.
3316.
91.
43(0.
85,2.
42)1.
30(0.
75,2.
25)DominantmodelAnyTvs.
CC16947.
619844.
21.
15(0.
87,1.
52)1.
22(0.
91,1.
63)RecessivemodelTTvs.
AnyC339.
3316.
91.
38(0.
83,2.
30)1.
20(0.
70,2.
06)AlleleORTvs.
C1.
15(0.
93,1.
43)1.
17(0.
93,1.
46)TP53rs1042522363446GG11832.
516136.
111CG14640.
219643.
91.
02(0.
74,1.
40)1.
07(0.
77,1.
50)CC9927.
38920.
01.
52(1.
05,2.
20)1.
63(1.
10,2.
41)DominantmodelAnyCvs.
GG24567.
528563.
91.
17(0.
88,1.
57)1.
24(0.
92,1.
69)RecessivemodelCCvs.
AnyG9927.
38920.
01.
50(1.
08,2.
09)1.
57(1.
11,2.
21)AlleleORCvs.
G1.
21(1.
01,1.
46)1.
26(1.
04,1.
53)*Adjustedforage,gender,education,packyearsofsmoking,alcoholdrinking,teadrinkingandaverageincome10yearsago.
Significantresultswerehighlightedinbold.
Figure1AssociationsofTP53rs2078486withlungcanceramongdifferentsubgroupswithdifferentage,gender,smokingstatus,alcoholandteadrinkingstatus,indoorairpollutionexposureandhisto-pathologicaltypesoflungcancer.
Adjustedage,gender,education,packyearsofsmoking,alcoholdrinking,teadrinkingandaverageincome10yearsago.
AC:adenocarcinoma,SCC:squamouscellcarcinoma;SmCC:smallcellcarcinoma.
AsterisksindicatesignificantORs.
Lietal.
BMCCancer2013,13:607Page4of9http://www.
biomedcentral.
com/1471-2407/13/6070.
99-3.
30)andadditiveinteraction(adjustedRERI:2.
49,95%CI:-0.
03,5.
01)(Table3).
Elevatedriskoflungcancerassociatedwithhomozy-gousvariantgenotype(CC)ofTP53SNPrs1042522wereobservedineachsubgroup.
Noobviousdifferencewasobservedbetweensmokersandnonsmokers(Figure2).
ThevariantgenotypeofTP53SNPrs1042522tendedtoconferstrongerdeleteriouseffectforyoungerindivid-uals,males,alcoholandteadrinkers,howeverneithermultiplicativenoradditiveinteractionswereobservedbetweenTP53SNPrs1042522andanylifestylefactorsonlungcancerrisk(Table3).
DiscussionThiscase–controlstudyconfirmedelevatedlungcancerriskassociatedwiththevariantallele(C)ofTP53SNPrs1042522,andthisstudyisamongthefirsttoreportatendencyofincreasedlungcancerriskassociatedwithvariantgenotypeofTP53SNPrs2078486inanAsianpopulation.
Moreover,wefoundsynergeticeffectsofsmokingandindoorairpollutionexposurewithTP53SNPrs2078486onlungcancerrisk.
OverwhelmingevidencesuggestedthattheTP53tumorsuppressorgeneisacentralregulatorynodeofmultiplecellularresponsepathwaystoendogenousorexogenousstresses[20].
P53proteinhasdemonstratedthecapacitytoregulateactivityofkeyeffectorsofcellu-larprocesses,suchasDNArepair,cellcyclearrest,sen-escence,andapoptosis[21,22].
FunctionalinactivationofP53pathwaysisthoughttoaffectP53signalingandfur-theraltercancerrisk[20,23].
TP53rs2078486SNPmightbeanovelTP53SNPaf-fectingriskofdevelopinglungcancer.
Onepathway-basedgenotypingstudyconductedamongnonsmokersfoundstatisticallysignificantassociationbetweenTP53rs2078486SNPandlungcancer[10].
Inthepresentstudy,wefoundsomesuggestiveevidenceofelevatedlungcancerriskassociatedwithTCorCCgenotypesofTP53rs2078486SNP(adjustedOR:1.
22,95%CI:0.
91-1.
63)intheoverallstudyparticipants.
Ourresultwasinsimilardirectionwithonepopulation-basedcase–con-trolstudyconductedinLosAngeles(adjustedOR:1.
61,95%CI:1.
18–2.
20)[11].
Thelesssignificantassociationobservedinourstudymightrelatetotherelativelysmallersamplesize.
Someothercase–controlstudiesalsosuggestedthatvariantgenotypeofTP53rs2078486SNPwassignificantlyassociatedwithincreasedrisksofovariancancerandschizophrenia[13,14,24].
Therefore,thissuggeststhattheremightbeafunctionaldifferenceamongdifferentgenotypesofTP53rs2078486SNP,whichmayaffecttheriskofdevelopingvarioustypesofcancersandotherhumandiseases.
TP53rs2078486islocatedinintron1andthusisnotlikelytobeadirectdisease-causingpolymorphism.
HoweverpreviousstudiessuggestthatTP53rs2078486isinalargelinkagedisequilibriumblockextendingfromupstreamofexon1tothefirsthalfofintron1[17].
ThereforeitispossiblethatTP53rs2078486mightbeinlinkagedisequilibriumwithsomefunctionalpolymor-phisms,whichinturnaltersusceptibilitytohumandis-eases.
SomeotherintronicvariationsinTP53werereportedtoaffectdiseaseriskpreviouslyandthemostwidelystudiedoneisTP53intron3duplicationpoly-morphism(rs17878362)[5,25].
Theunderlyingmechan-ismbywhichTP53rs2078486modulatescancerriskisnotfullyunderstoodandwarrantsfurtherinvestigations.
HoweverpriorstudiesprovidedsomeinitialevidencethatTP53rs2078486isinperfectlinkagedisequilibriumwithTP53rs2287498,whichispredictedtoaffectfunc-tionatasplicesiteandTP53rs2078486isalsoinweaklinkagedisequilibriumwithTP53rs12951953,whichmightaffectatranscriptionfactorbindingsite[13].
Moreover,wefoundcarryingthevariantallelesofTP53rs2078486SNPwassignificantlyassociatedwithelevatedlungcancerriskinsmokers(adjustedOR:1.
70,95%CI:1.
08-2.
67)andindividualswithhighindoorairpollutionexposure(adjustedOR:1.
51,95%CI:1.
00-2.
30).
CigarettesmokingandairpollutionhavebeenlinkedwithhighfrequencyofTP53mutations[26-29].
ThepositiveinteractionsobservedbetweenTP53SNPrs2078486withsmokingandindoorairpollutionexpos-ureinourstudymightsuggestthatindividualscarryingthevariantgenotypeofTP53rs2078486mayhavecom-promisedP53functionandrespondpoorlytothead-verseeffectsofsmokingandairpollution,thushaveanelevatedriskofdevelopinglungcancer.
Inaddition,theelevatedriskassociatedwithhigh-riskgenotypesTP53rs2078486SNPwasmoreevidentforthesmallcellcarcin-oma,whichhasbeenmorestronglylinkedtocigarettesmokingthantheotherhisto-pathologicaltypesoflungcancer.
ElevatedlungcancerriskassociatedwiththevariantCalleleofTP53SNPrs1042522observedinthisstudywasconsistentwithpreviousstudiesconductedamongtheAsianpopulations(summarizedORunderrecessivegen-eticmodel:1.
37,95%CI:1.
20–1.
57;homozygotecom-parisonCCvs.
GG:1.
34,95%CI:1.
16–1.
56)[8].
Inthepresentstudy,wedidnotfindheterogeneityoflungcan-cerrisksassociatedwithTP53SNPrs1042522insmokersversusnon-smokers,whichwasalsoconsistentwithapreviousmeta-analysis[8].
VeryfewpriorstudieshaveexaminedifdemographicorotherlifestylefactorsmightmodifytheassociationbetweenTP53SNPrs1042522andlungcancer.
Inthisstudy,wedidnotfindstatisticallysignificantinteractionsbetweenlifestylefactorsandTP53SNPrs1042522onlungcancerrisk.
Onemajorlimitationofthepresentstudyisthattherelativelysmallsamplesize,especiallyinthestratifiedLietal.
BMCCancer2013,13:607Page5of9http://www.
biomedcentral.
com/1471-2407/13/607Table3InteractionbetweenTP53SNPsandlifestylefactorsinTaiyuanlungcancerstudyCasesControlsCrudeOR(95%CI)AdjustedOR*(95%CI)Smokingrs2078486NoCC9514711NoTCorTT701270.
85(0.
58,1.
26)0.
93(0.
62,1.
39)YesCC911031.
37(0.
93,2.
00)3.
58(2.
02,6.
36)YesTCorTT99712.
16(1.
45,3.
22)6.
00(3.
33,10.
81)ORforinteraction1.
85(1.
05,3.
27)1.
80(0.
99,3.
30)RERI0.
94(0.
14,1.
74)2.
49(0.
03,5.
01)Alcoholdrinkingrs2078486NoCC14718411NoTCorTT1241481.
05(0.
76,1.
45)1.
06(0.
76,1.
48)YesCC39660.
74(0.
47,1.
16)0.
71(0.
42,1.
21)YesTCorTT45501.
13(0.
71,1.
78)1.
35(0.
79,2.
30)ORforinteraction1.
45(0.
76,2.
78)1.
79(0.
90,3.
58)RERI0.
34(0.
27,0.
95)0.
58(0.
15,1.
30)Teadrinkingrs2078486YesCC6510711YesTCorTT75911.
36(0.
88,2.
09)1.
44(0.
91,2.
28)NoCC1211431.
39(0.
94,2.
06)1.
43(0.
92,2.
22)NoTCorTT941071.
45(0.
96,2.
19)1.
51(0.
94,2.
41)ORforinteraction0.
77(0.
43,1.
35)0.
73(0.
40,1.
32)RERI0.
30(1.
08,0.
48)0.
37(1.
21,0.
48)Indoorairpollutionrs2078486LowCC6312411LowTCorTT411050.
77(0.
48,1.
23)0.
78(0.
48,1.
28)HighCC1071221.
73(1.
16,2.
57)1.
42(0.
92,2.
20)HighTCorTT104892.
30(1.
52,3.
48)2.
11(1.
35,3.
29)ORforinteraction1.
73(0.
94,3.
18)1.
89(1.
00,3.
56)RERI0.
81(0.
03,1.
65)0.
90(0.
11,1.
70)Smokingrs1042522NoGGorCG12021611NoCC48581.
49(0.
96,2.
32)1.
59(1.
00,2.
53)YesGGorCG1441411.
84(1.
33,2.
54)4.
73(2.
78,8.
04)YesCC51312.
96(1.
80,4.
88)8.
00(4.
08,15.
71)ORforinteraction1.
08(0.
55,2.
11)1.
07(0.
52,2.
18)RERI0.
63(0.
87,2.
14)2.
69(1.
64,7.
02)Alcoholdrinkingrs1042522NoGGorCG20026311NoCC74691.
41(0.
97,2.
05)1.
45(0.
98,2.
14)YesGGorCG64940.
90(0.
62,1.
29)0.
90(0.
57,1.
41)YesCC25201.
64(0.
89,3.
04)1.
86(0.
92,3.
76)ORforinteraction1.
30(0.
61,2.
80)1.
44(0.
63,3.
27)RERI0.
34(0.
78,1.
45)0.
52(0.
82,1.
86)Teadrinkingrs1042522YesGGorCG10015911Lietal.
BMCCancer2013,13:607Page6of9http://www.
biomedcentral.
com/1471-2407/13/607analyses,limitedourabilitytodetectmoderateinterac-tions.
Large-scaleepidemiologicalstudiesareneededinthefuturetoconfirmourfindings.
Second,afterconduct-ingBonferronicorrectionformultiplecomparisons,nosignificantinteractionsbetweenlifestylefactorsandTP53rs2078486SNPremained;thereforewecannotexcludethepossibilityofspuriousassociationsduetomultiplecomparisons.
Lastly,recallbiasislikelyforestablishedorprobableriskfactorsoflungcancer,suchassmokingandairpollution,inacase–controlstudy.
Howevertheasso-ciationbetweensmokingandlungcancerobservedinthecurrentstudyissimilartothepreviousstudiesconductedinanAsianpopulation[30].
Tominimizethepossiblere-callbiasonindoorairpollutionexposure,wecollectedinformationonseveralrelevantvariables,suchascook-ing,heatingandwindowopeningbehaviors.
Table3InteractionbetweenTP53SNPsandlifestylefactorsinTaiyuanlungcancerstudy(Continued)YesCC41351.
86(1.
11,3.
12)2.
09(1.
21,3.
61)NoGGorCG1641981.
32(0.
95,1.
82)1.
39(0.
95,2.
04)NoCC58541.
71(1.
09,2.
67)1.
81(1.
10,2.
97)ORforinteraction0.
70(0.
36,1.
36)0.
62(0.
31,1.
25)RERI0.
47(1.
62,0.
68)0.
67(1.
99,0.
65)Indoorairpollutionrs1042522LowGGorCG7318811LowCC33412.
07(1.
22,3.
53)1.
99(1.
14,3.
48)HighGGorCG1591632.
51(1.
78,3.
56)2.
04(1.
40,2.
99)HighCC56463.
14(1.
95,5.
04)2.
76(1.
66,4.
58)ORforinteraction0.
60(0.
30,1.
21)0.
68(0.
33,1.
41)RERI0.
45(2.
14,1.
24)0.
28(1.
88,1.
33)*Adjustedforage,gender,education,packyearsofsmoking,alcoholdrinking,teadrinkingandaverageincome10yearsago.
Significantresultswerehighlightedinbold.
Figure2AssociationsofTP53rs1042522withlungcanceramongdifferentsubgroupswithdifferentage,gender,smokingstatus,alcoholandteadrinkingstatus,indoorairpollutionexposureandhisto-pathologicaltypesoflungcancer.
AsterisksindicatesignificantORs.
AC:adenocarcinoma,SCC:squamouscellcarcinoma;SmCC:smallcellcarcinoma.
Adjustedage,gender,education,packyearsofsmoking,alcoholdrinking,teadrinkingandaverageincome10yearsago.
Lietal.
BMCCancer2013,13:607Page7of9http://www.
biomedcentral.
com/1471-2407/13/607ConclusionsInconclusion,thiscase–controlstudyprovidedprelim-inaryevidencethatTP53rs2078486SNPisanovelTP53SNPthatmayaffectlungcancerrisk,especiallyamongsmokersandindividualswithhighindoorairpol-lutionexposure.
Thereissomefurtherevidenceofsig-nificantinteractionsbetweenTP53rs2078486SNPandsmokingandindoorairpollutionexposureonlungcan-cerrisk.
Furtherstudieswithlargersamplesizeandindifferentstudypopulationsarewarrantedtoconfirmourfindings.
AbbreviationsSNPs:Single-nucleotidepolymorphisms;ORs:Oddsratios;95%CIs:95%confidenceintervals;RERI:Relativeexcessriskduetointeraction.
CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.
Authors'contributionsYLperformedthestatisticalanalysisanddraftedthemanuscript.
SCcarriedoutthegeneticpolymorphismtestsandhelpedtodraftthemanuscript.
RN,LL,BZ,JSandXHhavemadesubstantialcontributionstofieldworkanddatacollection.
CChelpedtodraftthemanuscript.
JL,JSandLCparticipatedinthedesignandcoordinationofthestudy.
SYandZZparticipatedinthedesignandfieldworkofthestudy.
LMoversawthestudydesign,resultsinterpretationandmanuscriptdrafting.
Allauthorsreadandapprovedthefinalmanuscript.
AcknowledgementsThisworkwassupportedinpartbytheNationalNatureScienceFoundationofChinagrantawardtoDr.
LinaMu(NSFC-30500417).
TheworkisalsopartiallysupportedbyNIHgrants(R01ES018846,ES06718,CA09142,DA11386)andtheAlperResearchCenterforEnvironmentalGenomicsoftheUCLAJonssonComprehensiveCancerCenter.
Authordetails1DepartmentofSocialandPreventiveMedicine,SchoolofPublicHealthandHealthProfessions,TheStateUniversityofNewYork(SUNY)atBuffalo,273AFarberHall,Buffalo,NewYork14214-8001,USA.
2DepartmentofEpidemiology,FieldingSchoolofPublicHealth,UniversityofCalifornia,LosAngeles(UCLA),LosAngeles,CA,USA.
3ShanxiTumorHospital,Taiyuan,Shanxi,Province,China.
4TaiyuanCityCenterforDiseaseControlandPrevention(CDC),Taiyuan,Shanxi,Province,China.
5SchoolofPublicHealth,FudanUniversity,Shanghai,China.
6DepartmentofEpidemiology,SchoolofPublicHealth,FujianMedicalUniversity,Fuzhou,Fijian,China.
Received:25March2013Accepted:18December2013Published:27December2013References1.
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doi:10.
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BMCCancer201313:607.
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