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Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

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Date
2014-01
Author
Pardini, Barbara
Verderio, Paolo
Pizzamiglio, Sara
Nici, Carmela
Maiorana, Maria Valeria
Naccarati, Alessio
Vodickova, Ludmila
Vymetalkova, Veronika
Veneroni, Silvia
Daidone, Maria Grazia
Ravagnani, Fernando
Bianchi, Tiziana
Bujanda Fernández de Pierola, Luis
Carracedo, Angel
Castells, Antoni
Ruiz Ponte, Clara
Morreau, Hans
Howarth, Kimberley
Jones, Angela
Castellví-Bel, Sergi
Li, Li
Tomlinson, Ian
Van Wezel, Tom
Vodicka, Pavel
Radice, Paolo
Peterlongo, Paolo
EPICOLON Consortium
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PloS ONE 9(1) : (2014) // e85538
URI
http://hdl.handle.net/10810/11879
Abstract
The common 2652 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 2652 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.
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