학술논문

MicroRNA related polymorphisms and breast cancer risk.
Document Type
article
Author
Sofia KhanDario GrecoKyriaki MichailidouRoger L MilneTaru A MuranenTuomas HeikkinenKirsimari AaltonenJoe DennisManjeet K BollaJianjun LiuPer HallAstrid IrwantoKeith HumphreysJingmei LiKamila CzeneJenny Chang-ClaudeRebecca HeinAnja RudolphPetra SeiboldDieter Flesch-JanysOlivia FletcherJulian PetoIsabel dos Santos SilvaNichola JohnsonLorna GibsonZoe AitkenJohn L HopperHelen TsimiklisMinh BuiEnes MakalicDaniel F SchmidtMelissa C SoutheyCarmel ApicellaJennifer StoneQuinten WaisfiszHanne Meijers-HeijboerMuriel A AdankRob B van der LuijtAlfons MeindlRita K SchmutzlerBertram Müller-MyhsokPeter LichtnerClare TurnbullNazneen RahmanStephen J ChanockDavid J HunterAngela CoxSimon S CrossMalcolm W R ReedMarjanka K SchmidtAnnegien BroeksLaura J Van't VeerFrans B HogervorstPeter A FaschingMichael G SchrauderArif B EkiciMatthias W BeckmannStig E BojesenBørge G NordestgaardSune F NielsenHenrik FlygerJavier BenitezPilar M ZamoraJose I A PerezChristopher A HaimanBrian E HendersonFredrick SchumacherLoic Le MarchandPaul D P PharoahAlison M DunningMitul ShahRobert LubenJudith BrownFergus J CouchXianshu WangCeline VachonJanet E OlsonDiether LambrechtsMatthieu MoisseRobert ParidaensMarie-Rose ChristiaensPascal GuénelThérèse TruongPierre Laurent-PuigClaire MulotFrederick MarmeBarbara BurwinkelAndreas SchneeweissChristof SohnElinor J SawyerIan TomlinsonMichael J KerinNicola MillerIrene L AndrulisJulia A KnightSandrine TchatchouAnna Marie MulliganThilo DörkNatalia V BogdanovaNatalia N AntonenkovaHoda Anton-CulverHatef DarabiMikael ErikssonMontserrat Garcia-ClosasJonine FigueroaJolanta LissowskaLouise BrintonPeter DevileeRobert A E M TollenaarCaroline SeynaeveChristi J van AsperenVessela N KristensenkConFab InvestigatorsAustralian Ovarian Cancer Study GroupSusan SlagerAmanda E TolandChristine B AmbrosoneDrakoulis YannoukakosAnnika LindblomSara MargolinPaolo RadicePaolo PeterlongoMonica BarilePaolo MarianiMaartje J HooningJohn W M MartensJ Margriet ColléeAgnes JagerAnna JakubowskaJan LubinskiKatarzyna Jaworska-BieniekKatarzyna DurdaGraham G GilesCatriona McLeanHiltrud BrauchThomas BrüningYon-Dschun KoGENICA NetworkHermann BrennerAida Karina DieffenbachVolker ArndtChrista StegmaierAnthony SwerdlowAlan AshworthNick OrrMichael JonesJacques SimardMark S GoldbergFrance LabrècheMartine DumontRobert WinqvistKatri PylkäsArja Jukkola-VuorinenMervi GripVesa KatajaVeli-Matti KosmaJaana M HartikainenArto MannermaaUte HamannGeorgia Chenevix-TrenchCarl BlomqvistKristiina AittomäkiDouglas F EastonHeli Nevanlinna
Source
PLoS ONE, Vol 9, Iss 11, p e109973 (2014)
Subject
Medicine
Science
Language
English
ISSN
1932-6203
Abstract
Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.