Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F23%3A00580684" target="_blank" >RIV/68378041:_____/23:00580684 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/23:10464170 RIV/00216208:11120/23:43925432 RIV/00216208:11140/23:10464170 RIV/61989592:15110/23:73621202 RIV/00064173:_____/23:43925432

Result on the web

<a href="https://jmg.bmj.com/content/60/10/980" target="_blank" >https://jmg.bmj.com/content/60/10/980</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jmg-2022-108910" target="_blank" >10.1136/jmg-2022-108910</a>

Result language

angličtina

Original language name

Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

Original language description

Introduction Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues, nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate. Materials and methods We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase. Results The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93x10(-8) in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a C-phosphate-G (CpG) site located in the promoter region of the RCCD1 antisense (RCCD1-AS1) gene which, when expressed, decreases the expression of the RCC1 domain-containing (RCCD1) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of RCCD1 gene expression, made possible by the inactivity of RCCD1-AS1. Conclusion We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation.

Czech name

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Czech description

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Type

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

CEP classification

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OECD FORD branch

30101 - Human genetics

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Journal of Medical Genetics

ISSN

0022-2593

e-ISSN

1468-6244

Volume of the periodical

60

Issue of the periodical within the volume

10

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

980-986

UT code for WoS article

001012068200001

EID of the result in the Scopus database

2-s2.0-85159235636