Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
;
Isabel Dos-Santos-Silva ;
OliviaFletcher;
NicholaJohnson;
HeliNevanlinna;
Taru AMuranen;
KristiinaAittomäki;
CarlBlomqvist;
JingmeiLi;
KeithHumphreys;
JudithBrand;
PascalGuénel;
ThérèseTruong;
EmilieCordina-Duverger;
FlorenceMenegaux;
BarbaraBurwinkel;
FrederikMarme;
RongxiYang;
HaraldSurowy;
JavierBenitez;
M PilarZamora;
Jose IAPerez;
AngelaCox;
Simon SCross;
Malcolm WRReed;
Irene LAndrulis;
Julia AKnight;
GordGlendon;
SandrineTchatchou;
Elinor JSawyer;
IanTomlinson;
Michael JKerin;
NicolaMiller;
GeorgiaChenevix-Trench;
kConFab Investigators, Australian Ovarian Study Group;
Christopher AHaiman;
Brian EHenderson;
FredrickSchumacher;
Loic LeMarchand;
AnnikaLindblom;
SaraMargolin;
Maartje JHooning;
John WMMartens;
Madeleine MATilanus-Linthorst;
J MargrietCollée;
John LHopper;
Melissa CSouthey;
HelenTsimiklis;
CarmelApicella;
SusanSlager;
Amanda EToland;
Christine BAmbrosone;
DrakoulisYannoukakos;
Graham GGiles;
Roger LMilne;
CatrionaMcLean;
Peter AFasching;
LotharHaeberle;
Arif BEkici;
Matthias WBeckmann;
HermannBrenner;
Aida KarinaDieffenbach;
VolkerArndt;
ChristaStegmaier;
Anthony JSwerdlow;
AlanAshworth;
NickOrr;
MichaelJones;
JonineFigueroa;
MontserratGarcia-Closas;
LouiseBrinton;
JolantaLissowska;
MartineDumont;
RobertWinqvist;
KatriPylkäs;
ArjaJukkola-Vuorinen;
MerviGrip;
HiltrudBrauch;
ThomasBrüning;
Yon-DschunKo;
PaoloPeterlongo;
SiranoushManoukian;
BernardoBonanni;
PaoloRadice;
NataliaBogdanova;
NataliaAntonenkova;
ThiloDörk;
ArtoMannermaa;
VesaKataja;
Veli-MattiKosma;
Jaana MHartikainen;
PeterDevilee;
CarolineSeynaeve;
Christi JVan Asperen;
AnnaJakubowska;
JanLubiński;
KatarzynaJaworska-Bieniek;
KatarzynaDurda;
UteHamann;
DianaTorres;
Rita KSchmutzler;
Susan LNeuhausen;
HodaAnton-Culver;
Vessela NKristensen;
Grethe IGrenaker Alnæs;
DRIVE Project;
Brandon LPierce;
PeterKraft;
UlrikePeters;
SaraLindstrom;
DanielaSeminara;
StephenBurgess;
HabibulAhsan;
Alice SWhittemore;
Esther MJohn;
Marilie DGammon;
Kathleen EMalone;
Daniel CTessier;
DanielVincent;
FrancoisBacot;
CraigLuccarini;
CarolineBaynes;
ShahanaAhmed;
MelMaranian;
Catherine SHealey;
AnnaGonzález-Neira;
GuillermoPita;
M RosarioAlonso;
NuriaÁlvarez;
DanielHerrero;
Paul DPPharoah;
JacquesSimard;
PerHall;
David JHunter;
Douglas FEaston;
WeiZheng;
(2015)
Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
Journal of the National Cancer Institute, 107 (11).
djv219-djv219.
ISSN 0027-8874
DOI: 10.1093/jnci/djv219
BACKGROUND: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. RESULTS: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8). CONCLUSIONS: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643630 (OA Location)
- 10.1093/jnci/djv219 (DOI)
- 26296642 (PubMed)