Association between CASP8 -652 6N del polymorphism (rs3834129) and colorectal cancer risk: results from a multi-centric study.
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.
Genomic Variation in Human Populations and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy.
Barbara
B
Pardini
Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Paolo
P
Verderio
Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Sara
S
Pizzamiglio
Fondazione Istituto Italian Foundation for Cancer Research di Oncologia Molecolare, Milan, Italy.
Carmela
C
Nici
Fondazione Istituto Italian Foundation for Cancer Research di Oncologia Molecolare, Milan, Italy.
Maria Valeria
MV
Maiorana
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.
Alessio
A
Naccarati
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic ; First Medical Faculty, Charles University, Prague, Czech Republic.
Ludmila
L
Vodickova
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic ; First Medical Faculty, Charles University, Prague, Czech Republic.
Veronika
V
Vymetalkova
Department of Experimental Oncology and Molecular Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Silvia
S
Veneroni
Department of Experimental Oncology and Molecular Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Maria Grazia
MG
Daidone
Immunohematology and Transfusion Medicine Service, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Fernando
F
Ravagnani
Associazione Italiana Volontari Sangue Comunale Milano, Milan, Italy.
Tiziana
T
Bianchi
Gastroenterology Department, Hospital Donostia, Networked Biomedical Research Centre for Hepatic and Digestive Diseases, Basque Country University, San Sebastián, Spain.
Luis
L
Bujanda
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.
Angel
A
Carracedo
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.
Antoni
A
Castells
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.
Clara
C
Ruiz-Ponte
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Hans
H
Morreau
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.
Kimberley
K
Howarth
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.
Angela
A
Jones
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.
Sergi
S
Castellví-Bel
Department of Family Medicine and Community Health and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
Li
L
Li
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.
Ian
I
Tomlinson
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Tom
T
Van Wezel
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic ; First Medical Faculty, Charles University, Prague, Czech Republic.
Pavel
P
Vodicka
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.
Paolo
P
Radice
Fondazione Istituto Italian Foundation for Cancer Research di Oncologia Molecolare, Milan, Italy.
Paolo
P
Peterlongo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012306:Risk; D017384:Sequence Deletion; D044465:White People
C505530:CASP8 protein, human; D053181:Caspase 8