Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00552790" target="_blank" >RIV/68378041:_____/21:00552790 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11120/21:43921764 RIV/00216208:11140/21:10429094 RIV/00216208:11110/21:10429094 RIV/00064173:_____/21:N0000128 RIV/61989592:15110/21:73608705
Result on the web
<a href="https://academic.oup.com/carcin/article-abstract/42/8/1037/6314283?redirectedFrom=fulltext" target="_blank" >https://academic.oup.com/carcin/article-abstract/42/8/1037/6314283?redirectedFrom=fulltext</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/carcin/bgab057" target="_blank" >10.1093/carcin/bgab057</a>
Alternative languages
Result language
angličtina
Original language name
Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma
Original language description
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 x 10(-10)). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 x 10(-6)). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
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
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
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
42
Issue of the periodical within the volume
8
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
1037-1045
UT code for WoS article
000692322000004
EID of the result in the Scopus database
2-s2.0-85114637768