Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00604389" target="_blank" >RIV/68378041:_____/25:00604389 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/25:10485351 RIV/00216208:11110/25:10485351 RIV/00216208:11120/25:43927600 RIV/00064173:_____/25:43927600 and 2 more

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/10.1002/ijc.35196" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/ijc.35196</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.35196" target="_blank" >10.1002/ijc.35196</a>

Result language

angličtina

Original language name

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization

Original language description

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10−6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10−8 and OR = 1.16, p = 2.74 × 10−5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10−4 and p = 1.56 × 10−3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10−4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

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

—

OECD FORD branch

30204 - Oncology

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)

Publication year

2025

Confidentiality

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

Name of the periodical

International Journal of Cancer

ISSN

0020-7136

e-ISSN

1097-0215

Volume of the periodical

156

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

339-352

UT code for WoS article

001319126300001

EID of the result in the Scopus database

2-s2.0-85205246523