The common -652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant -652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

Associazione Italiana Volontari Sangue Comunale Milano Milan Italy

Department of Experimental Oncology and Molecular Medicine Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Department of Family Medicine and Community Health and Case Comprehensive Cancer Center Case Western Reserve University Cleveland Ohio United States of America

Department of Gastroenterology Hospital Clínic Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Catalonia Spain

Department of Molecular Biology of Cancer Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic ; 1st Medical Faculty Charles University Prague Czech Republic

Department of Pathology Leiden University Medical Center Leiden The Netherlands

Fondazione Istituto Italian Foundation for Cancer Research di Oncologia Molecolare Milan Italy

Galician Public Foundation of Genomic Medicine Centro de Investigación Biomédica en Red de Enfermedades Raras Genomics Medicine Group Hospital Clínico Santiago de Compostela University of Santiago de Compostela Galicia Spain

Gastroenterology Department Hospital Donostia Networked Biomedical Research Centre for Hepatic and Digestive Diseases Basque Country University San Sebastián Spain

Genomic Variation in Human Populations and Complex Diseases Unit Human Genetics Foundation Turin Italy

Immunohematology and Transfusion Medicine Service Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Molecular and Genetic Epidemiology Unit Human Genetics Foundation Turin Italy ; Department of Molecular Biology of Cancer Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

Molecular and Population Genetics Laboratory and National Institute for Health Research Comprehensive Biomedical Research Centre Wellcome Trust Centre for Human Genetics University of Oxford Oxford United Kingdom

Unit of Medical Statistics Biometry and Bioinformatics Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Unit of Molecular Bases of Genetic Risk and Genetic Testing Department of Preventive and Predictive Medicine Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

PLoS One. 2014;9(3):e91310 PubMed

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