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@ARTICLE{Campa:141291,
author = {D. Campa and M. Matarazzi$^*$ and W. Greenhalf and M.
Bijlsma and K.-U. Saum$^*$ and C. Pasquali and H. van
Laarhoven and A. Szentesi and F. Federici and P. Vodicka and
N. Funel and R. Pezzilli and H. B. Bueno-de-Mesquita and L.
Vodickova and D. Basso and O. Obazee$^*$ and T. Hackert and
P. Soucek and K. Cuk$^*$ and J. Kaiser and C. Sperti and M.
Lovecek and G. Capurso and B. Mohelnikova-Duchonova and
K.-T. Khaw and A.-K. König and J. Kupcinskas and R.
Kaaks$^*$ and F. Bambi and L. Archibugi and A. Mambrini and
G. M. Cavestro and S. Landi and P. Hegyi and J. R. Izbicki
and D. Gioffreda and C. F. Zambon and F. Tavano and R.
Talar-Wojnarowska and K. Jamroziak and T. J. Key and G. D.
Fave and O. Strobel and L. Jonaitis and A. Andriulli and R.
T. Lawlor and F. Pirozzi and V. Katzke$^*$ and C. Valsuani
and Y. K. Vashist and H. Brenner$^*$ and F. Canzian$^*$},
title = {{G}enetic determinants of telomere length and risk of
pancreatic cancer: a {PAND}o{RA} study.},
journal = {International journal of cancer},
volume = {144},
number = {6},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2018-01811},
pages = {1275-1283},
year = {2019},
abstract = {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 = 1.54x10-10 ) and a novel one with the NAF1-rs7675998
SNP (OR = 0.80; $95\%CI$ 0.73-0.88; p = 1.87x10-6 ,
ptrend = 3.27x10-7 ). The association of short LTL,
measured by the teloscore, with PDAC risk reached
genome-wide significance (p = 2.98x10-9 for highest vs.
lowest quintile; p = 1.82x10-10 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. This article is
protected by copyright. All rights reserved.},
cin = {C055 / C070 / C120 / C020 / L101},
ddc = {610},
cid = {I:(DE-He78)C055-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)C020-20160331 /
I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30325019},
doi = {10.1002/ijc.31928},
url = {https://inrepo02.dkfz.de/record/141291},
}