6533b82cfe1ef96bd128f473
RESEARCH PRODUCT
Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility
S. PicelliJ. Lorenzo BermejoJ. Chang ClaudeM. HoffmeisterC. Fernández RozadillaA. CarracedoA. CastellsS. Castellví BelD.m. JuanM. RaquelM. MarisaC. FranciscoD. JoseI. CarolinaL. GuadalupeI. AlbertoC. AntoniP. VirgíniaC.b. SergiF. BalaguerG. VictoriaO. TeresaG. María DoloresP. MariaS. AnnaM. LeticiaC. MiriamM.p. JosepA. LanasJ. AlcedoF.j. OrtegoC. JoaquinS.d. MaS. MercedesS. EloyV. MarianoA. MontserratA. AnnaB. XavierI. MarS. AgustínB. FelipeN. GemmaB. BeatrizM. De JosepÁ. CristinaP. MarcB. LuisC. ÁNgelG. InésL. MikelP. CarlosD.m.r. MaríaH. ElisabethM.e.n. JoseL.e. JoseP. ArtemioJ. RodrigoA. CristinaS. LauraA. NuriaR. EstefaníaP.c. LucíaR. JoaquimS. ÁNgelG. AnnaS. JoanB.a. EduardA. JosefinaB. RamonM.g. AnaC. FernandoB. AntonioS. EduardoG. FernandoS. JaimeO. AkikoL. MercedesM. EnriqueC. JaimeC. PilarM. MiguelA.g. JoséQ. FranciscoO. ElisaC. JuanS. JaimeT. AntoniS. EugeniaL.c. De MaT. AntoniC. JuanH. VicentL. XavierM.x. RosaP. MartaR. MercèR. AnnaP. ElisendaM.h. JoséA.g. MiquelF.b. FernandoM.v. JosepS. AntonioE. JorgeF. MontserratE. MariaM.r. JosepP. CarmenB. JuanV. JoanQ. EnriqueN. DavidP. AdolfoM. AntonioA. LidiaP. VicenteP. VirginiaS. TeresaG. DolorsR. EvaR. TeresaP. MariaM.c. MaM. MartaP. LourdesM. DanielC. ÁNgelR.p. ClaraF.r. CeresM.c. MaR. SabinoR. LuisF. JavierL.c. JoseC. LuisO. SusanaB. FedericoP. ElenaM.b. JoséC. GloriaJ.s. JuanN. AntonioA. NaccaratiB. PardiniL. VodickovaH. MüllerB.a. Talseth PalmerG. StibbardP. PeterlongoC. NiciS. VeneroniL. LiG. CaseyA. TenesaS.m. FarringtonI. TomlinsonV. MorenoT. Van WezelJ. WijnenM. DunlopP. RadiceR.j. ScottP. VodickaC. Ruiz PonteH. BrennerS. BuchH. VölzkeJ. HampeC. SchafmayerA. Lindblomsubject
Linkage disequilibriumGenotypeReparació de l'ADNlcsh:MedicineDNA repairGenome-wide association studySingle-nucleotide polymorphismBiologyGenetic polymorphismsDNA Mismatch RepairPolymorphism Single NucleotideDNA Glycosylases03 medical and health sciences0302 clinical medicineMUTYHCàncer colorectalHumansGenetic Predisposition to Diseaselcsh:ScienceGenetic Association Studies030304 developmental biologyGenetic associationGenetics0303 health sciencesMultidisciplinaryGenetic heterogeneityPolimorfisme genèticlcsh:RCase-control studyOdds ratioColorectal cancer3. Good health030220 oncology & carcinogenesisCase-Control Studieslcsh:QColorectal NeoplasmsResearch Articledescription
In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a followup of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-09-06 |