Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F19%3A73596471" target="_blank" >RIV/61989592:15110/19:73596471 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/19:00495333 RIV/00216208:11110/19:10378632 RIV/00216208:11140/19:10378632

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31928" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31928</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.31928" target="_blank" >10.1002/ijc.31928</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Popis výsledku v původním jazyce

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score (&quot;teloscore&quot;, which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 x 10(-10)) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 x 10(-6), p(trend) = 3.27 x 10(-7)). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 x 10(-9) for highest vs. lowest quintile; p = 1.82 x 10(-10) as a continuous variable).

Název v anglickém jazyce

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Popis výsledku anglicky

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score (&quot;teloscore&quot;, which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 x 10(-10)) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 x 10(-6), p(trend) = 3.27 x 10(-7)). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 x 10(-9) for highest vs. lowest quintile; p = 1.82 x 10(-10) as a continuous variable).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

—

Rok uplatnění

2019

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

14

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

1275-1283

Kód UT WoS článku

000459321900007

EID výsledku v databázi Scopus

2-s2.0-85056475056