A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F23%3A10467596" target="_blank" >RIV/00216208:11140/23:10467596 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10467596 RIV/00216208:11120/23:43926014 RIV/00064173:_____/23:43926014 RIV/00098892:_____/23:10158459 and 2 more
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RLpV.9jcVh" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RLpV.9jcVh</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/carcin/bgad056" target="_blank" >10.1093/carcin/bgad056</a>
Alternative languages
Result language
angličtina
Original language name
A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma
Original language description
Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case control study comprising four different populations, for a total of 14,538 PDAC cases and 190,657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P=2.46x10 -9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P=1.53x10 -6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of GWAS studies in light of functional data.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Carcinogenesis
ISSN
0143-3334
e-ISSN
1460-2180
Volume of the periodical
44
Issue of the periodical within the volume
8-9
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
642-649
UT code for WoS article
001068185500001
EID of the result in the Scopus database
2-s2.0-85178662996