May 5, 2014
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Article

Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility

Publicated to:Plos One. 8 (9): e72091- - 2013-09-06 8(9), DOI: 10.1371/journal.pone.0072091

Authors: Picelli, Simone; Lorenzo Bermejo, Justo; Chang-Claude, Jenny; Hoffmeister, Michael; Fernandez-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellvi-Bel, Sergi; Naccarati, Alessio; Pardini, Barbara; Vodickova, Ludmila; Mueller, Heiko; Talseth-Palmer, Bente A; Stibbard, Geoffrey; Peterlongo, Paolo; Nici, Carmela; Veneroni, Silvia; Li, Li; Casey, Graham; Tenesa, Albert; Tomlinson, Ian; Moreno, Victor; van Wezel, Tom; Wijnen, Juul; Radice, Paolo; Scott, Rodney J; Vodicka, Pavel; Brenner, Hermann; Buch, Stephan; Voelzke, Henry; Hampe, Jochen; Schafmayer, Clemens; Lindblom, Annika

Affiliations

Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic - Author
Case Western Reserve Univ, Case Comprehens Canc Ctr, Case Ctr Transdisciplinary Res Energet & Canc, Dept Family Med, Cleveland, OH 44106 USA - Author
Charles Univ Prague, Fac Med 1, Prague, Czech Republic - Author
CIBERESP, IDIBELL, ICO, Barcelona, Spain - Author
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy - Author
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy - Author
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany - Author
German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany - Author
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany - Author
Hunter Med Res Inst, Newcastle, NSW, Australia - Author
Ist FIRC Oncol Mol, Fdn IFOM, Milan, Italy - Author
John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia - Author
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden - Author
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands - Author
Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands - Author
Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands - Author
Ludwig Inst Canc Res, Stockholm Branch, S-10401 Stockholm, Sweden - Author
MRC Human Genet Unit, Edinburgh, Midlothian, Scotland - Author
Oxford NIHR Comprehens Biomed Res Ctr, Oxford, England - Author
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBERehd,IDIBAPS, Barcelona, Spain - Author
Univ Barcelona, Hosp Llobregat, Barcelona, Spain - Author
Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp, Edinburgh, Midlothian, Scotland - Author
Univ Heidelberg Hosp, Inst Med Biometry & Informat, Heidelberg, Germany - Author
Univ Hosp Schleswig Holstein, Dept Gen Internal Med, Kiel, Germany - Author
Univ Kiel, Dept Gen & Thorac Surg, Kiel, Germany - Author
Univ Med Greifswald, Inst Community Med, Greifswald, Germany - Author
Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia - Author
Univ Newcastle, Sch Sci & IT, Newcastle, NSW 2300, Australia - Author
Univ Santiago de Compostela, Hosp Clin, Genom Med Grp, CIBERER,FPGMX, Galicia, Spain - Author
Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA - Author
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Abstract

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 follow-up 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.

Keywords

adenomatous polyposisgenome-wide associationjapanese populationmutationsmutyhmyhrisktumorsvariantsBase-excision-repairCase-control studiesColorectal neoplasmsDna glycosylasesDna mismatch repairFollow-upGenetic association studiesGenetic predisposition to diseaseGenotypeHumansMutationsMuty adenine glycosylasePolymorphism, single nucleotidePopulationPrevalenceRiskTumorsVariants

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Plos One due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2013, it was in position 8/55, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1.17, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 2.19 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-26, the following number of citations:

  • WoS: 21
  • Scopus: 21
  • Europe PMC: 16

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 52.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 52 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Australia; Czech Republic; Germany; Italy; Netherlands; San Francisco; Sweden; United Kingdom; United States of America.