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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F19%3A00495333" target="_blank" >RIV/68378041:_____/19:00495333 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10378632 RIV/00216208:11140/19:10378632 RIV/61989592:15110/19:73596471

Result on the web

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

Result language

angličtina

Original language name

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

Original language description

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 (teloscore, 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). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

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

30101 - Human genetics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

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

—

Volume of the periodical

144

Issue of the periodical within the volume

6

Country of publishing house

DE - GERMANY

Number of pages

9

Pages from-to

1275-1283

UT code for WoS article

000459321900007

EID of the result in the Scopus database

2-s2.0-85056475056