decreasing effect sizes with increasing collections of individuals, a
phenomenon well-known in the field of genetic epidemiology
denominated the winner’s curse [21]. It should be kept in mind
that this outcome is rather expected in association studies, in
particular those dealing with regionally heterogeneous complex
diseases.
Supporting Information
Table S1 Number of cases and controls genotyped in
the fourteen studies.
(DOC)
Table S2 Genotype counts and allele frequencies for
rs459552 (APC D1822V), rs1799977 (MLH I219V),
rs1800932 (MSH6 P92P), rs1800935 (MSH6 D180D),
rs3219484 (MUTYH V22M) and rs3219489 (MUTYH
Q338H). The estimated odds ratios with 95% confidence
intervals for individual studies are also shown, together with
combined ORs, 95% CIs and probability values for OR = 1 based
on random effects model and probability values for study
homogeneity under dominant, additive and recessive penetrance.
(DOC)
Table S3 Genotype counts and allele frequencies for
rs3219489 (MUTYH Q338H).
(DOC)
Table S4 Genotype counts for colon and rectal cancer
cases in studies with available information on tumor
location.
(DOC)
Acknowledgments
We thank all the patients that participated in this study. Members of the
EPICOLON Consortium (Gastrointestinal Oncology Group of
the Spanish Gastroenterological Association):
Hospital 12 de Octubre, Madrid: Juan Diego Morillas (local coordina-
tor), Raquel Mun˜oz, Marisa Manzano, Francisco Colina, Jose Dı
´az,
Carolina Ibarrola, Guadalupe Lo´pez, Alberto Iba´n˜ez; Hospital Clı
´nic,
Barcelona: Antoni Castells (local coordinator), Virgı
´nia Pin˜ol, Sergi
Castellvı
´-Bel, Francesc Balaguer, Victoria Gonzalo, Teresa Ocan˜a, Marı
´a
Dolores Gira´ldez, Maria Pellise´, Anna Serradesanferm, Leticia Moreira,
Miriam Cuatrecasas, Josep M. Pique´; Hospital Clı
´nico Universitario,
Zaragoza: A
´ngel Lanas (local coordinator), Javier Alcedo, Javier Ortego;
Hospital Cristal-Pin˜or, Complexo Hospitalario de Ourense: Joaquin
Cubiella (local coordinator), M
a
Soledad Dı
´ez, Mercedes Salgado, Eloy
Sa´nchez, Mariano Vega; Parc de Salut Mar, Barcelona: Montserrat
Andreu (local coordinator), Anna Abuli, Xavier Bessa, Mar Iglesias,
Agustı
´n Seoane, Felipe Bory, Gemma Navarro, Beatriz Bellosillo; Josep M
a
Dedeu, Cristina A
´lvarez, Marc Puigvehı
´; Hospital San Eloy, Baracaldo
and Hospital Donostia, CIBERehd, University of Basque Country, San
Sebastia´n: Luis Bujanda (local coordinator) A
´ngel Cosme, Ine´s Gil, Mikel
Larzabal, Carlos Placer, Marı
´a del Mar Ramı
´rez, Elisabeth Hijona, Jose
M. Enrı
´quez-Navascue´s, Jose L. Elosegui; Hospital General Universitario
de Alicante: Artemio Paya´ (EPICOLON I local coordinator), Rodrigo
Jover (EPICOLON II local coordinator), Cristina Alenda, Laura Sempere,
Nuria Acame, Estefanı
´a Rojas, Lucı
´aPe´rez-Carbonell; Hospital General
de Granollers: Joaquim Rigau (local coordinator), A
´ngel Serrano, Anna
Gime´nez; Hospital General de Vic: Joan Salo´ (local coordinator), Eduard
Batiste-Alentorn, Josefina Autonell, Ramon Barniol; Hospital General
Universitario de Guadalajara and Fundacio´n para la Formacio´n e
Investigacio´n Sanitarias Murcia: Ana Marı
´a Garcı
´a (local coordinator),
Fernando Carballo, Antonio Bienvenido, Eduardo Sanz, Fernando
Gonza´lez, Jaime Sa´nchez, Akiko Ono; Hospital General Universitario de
Valencia: Mercedes Latorre (local coordinator), Enrique Medina, Jaime
Cuquerella, Pilar Canelles, Miguel Martorell, Jose´A
´ngel Garcı
´a, Francisco
Quiles, Elisa Orti; CHUVI-Hospital Meixoeiro, Vigo: EPICOLON I: Juan
Clofent (local coordinator), Jaime Seoane, Antoni Tardı
´o, Eugenia
Sanchez. EPICOLON II M
a
Luisa de Castro (local coordinator), Antoni
Tardı
´o, Juan Clofent, Vicent Herna´ndez; Hospital Universitari Germans
Trias i Pujol, Badalona and Section of Digestive Diseases and Nutrition,
University of Illinois at Chicago, IL, USA: Xavier Llor (local coordinator),
Rosa M. Xicola, Marta Pin˜ol, Merce` Rosinach, Anna Roca, Elisenda
Pons, Jose´ M. Herna´ndez, Miquel A. Gassull; Hospital Universitari Mu´tua
de Terrassa: Fernando Ferna´ndez-Ban˜ares (local coordinator), Josep M.
Viver, Antonio Salas, Jorge Espino´s, Montserrat Forne´, Maria Esteve;
Hospital Universitari Arnau de Vilanova, Lleida: Josep M. Ren˜e´ (local
coordinator), Carmen Pin˜ ol, Juan Buenestado, Joan Vin˜as; Hospital
Universitario de Canarias: Enrique Quintero (local coordinator), David
Nicola´s, Adolfo Parra, Antonio Martı
´n; Hospital Universitario La Fe,
Valencia: Lidia Argu¨ello (local coordinator), Vicente Pons, Virginia
Pertejo, Teresa Sala; Hospital Sant Pau, Barcelona: Dolors Gonzalez
(local coordinator) Eva Roman, Teresa Ramon, Maria Poca, M
a
Mar
Concepcio´ n, Marta Martin, Lourdes Pe´triz; Hospital Xeral Cies, Vigo:
Daniel Martinez (local coordinator); Fundacion Publica Galega de
Medicina Xenomica (FPGMX), CIBERER, Genomic Medicine Group-
University of Santiago de Compostela, Santiago de Compostela, Galicia,
Spain: A
´ngel Carracedo (local coordinator), Clara Ruiz-Ponte, Ceres
Ferna´ndez-Rozadilla, M
a
Magdalena Castro; Hospital Universitario
Central de Asturias: Sabino Riestra (local coordinator), Luis Rodrigo;
Hospital de Galda´cano, Vizcaya: Javier Ferna´ndez (local coordinator), Jose
Luis Cabriada; Fundacio´n Hospital de Calahorra (La Rioja) La Rioja: Luis
Carren˜ o (local coordinator), Susana Oquin˜ena, Federico Bolado; Hospital
Royo Villanova, Zaragoza: Elena Pen˜a (local coordinator), Jose´ Manuel
Blas, Gloria Cen˜ a, Juan Jose´ Sebastia´n; Hospital Universitario Reina Sofı
´a,
Co´rdoba: Antonio Naranjo (local coordinator).
Author Contributions
Conceived and designed the experiments: AL. Performed the experiments:
SP JCC MH CFR A. Carracedo A. Castells SCB AN BP LV HM BTP GS
PP CN SV LL GC AT SMF IT VM TVW JW MD PR RJS PV CRP HB
SB HV JH CS. Analyzed the data: SP JLB. Contributed reagents/
materials/analysis tools: AL JLB JCC MH CFR A. Carracedo A. Castells
SCB AN BP LV HM BTP GS PP CN SV LL GC AT SMF IT VM TVW
JW MD PR RJS PV CRP HB SB HV JH CS EPICOLON Consortium.
Wrote the paper: SP JLB AL.
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Meta-Analysis of Mismatch Repair SNPs in CRC
PLOS ONE | www.plosone.org 5 September 2013 | Volume 8 | Issue 9 | e72091