Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F21%3A10435477" target="_blank" >RIV/00216208:11140/21:10435477 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11120/21:43922687 RIV/00216208:11110/21:10435477 RIV/65269705:_____/21:00075825 RIV/00064173:_____/21:N0000123 and 4 more

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=6KNgYN_Luv" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=6KNgYN_Luv</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2021.771312" target="_blank" >10.3389/fonc.2021.771312</a>

Result language

angličtina

Original language name

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Original language description

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p&lt;10(-5)) compared with the additive effects (p&gt;10(-3)), although none of the six SNPs reached the conventional threshold for genome-wide significance (p &lt; 5x10(-8)). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NV19-03-00097" target="_blank" >NV19-03-00097: The analysis of unique rare entities of pancreatic ductal adenocarcinoma</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Oncology [online]

ISSN

2234-943X

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

December

Country of publishing house

CH - SWITZERLAND

Number of pages

10

Pages from-to

771312

UT code for WoS article

000761072100001

EID of the result in the Scopus database

2-s2.0-85121395745