Genome-wide association study identifies an early onset pancreatic cancer risk locus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F20%3AN0000195" target="_blank" >RIV/00064173:_____/20:N0000195 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/20:00538992 RIV/00216208:11110/20:10411103 RIV/00216208:11120/20:43920054 RIV/00216208:11140/20:10411103 RIV/75010330:_____/20:00013326

Výsledek na webu

<a href="https://doi.org/10.1002/ijc.33004" target="_blank" >https://doi.org/10.1002/ijc.33004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.33004" target="_blank" >10.1002/ijc.33004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genome-wide association study identifies an early onset pancreatic cancer risk locus

Popis výsledku v původním jazyce

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset <= 60 years, of whom 198 with age of onset <= 50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 x 10(-4)). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset <= 60 years, of whom 265 with age of onset <= 50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 x 10(-4)). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

Název v anglickém jazyce

Genome-wide association study identifies an early onset pancreatic cancer risk locus

Popis výsledku anglicky

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset <= 60 years, of whom 198 with age of onset <= 50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 x 10(-4)). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset <= 60 years, of whom 265 with age of onset <= 50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 x 10(-4)). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV19-03-00097" target="_blank" >NV19-03-00097: Studium specifických podskupin u pacientů s adenokarcinomem pankreatu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Cancer

ISSN

0020-7136

e-ISSN

1097-0215

Svazek periodika

147

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

2065-2074

Kód UT WoS článku

000529605800001

EID výsledku v databázi Scopus

2-s2.0-85084206474