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@ARTICLE{Srinivas:143386,
author = {N. Srinivas$^*$ and S. Rachakonda$^*$ and T. Hielscher$^*$
and S. Calderazzo and P. Rudnai and E. Gurzau and K. Koppova
and T. Fletcher and R. Kumar$^*$},
title = {{T}elomere length, arsenic exposure and risk of basal cell
carcinoma of skin.},
journal = {Carcinogenesis},
volume = {40},
number = {6},
issn = {1460-2180},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2019-00974},
pages = {715-723},
year = {2019},
abstract = {Telomere length per se a heritable trait has been reported
to be associated with different diseases including cancers.
In this study based on arsenic exposed 528 cases with basal
cell carcinoma of skin (BCC) and 533 healthy controls we
investigated effect of telomere length, measured by
real-time PCR, on the disease risk. We observed a
statistically significant association between decreased
telomere length and increased BCC risk (OR = 5.92, $95\%$ CI
= 3.92-9.01, P<0.0001). Due to confounder effect of arsenic
exposure, in a two-sample Mendelian randomization (MR),
telomere-length associated single nucleotide polymorphisms
as instrument variables violated valid assumptions; however,
one-sample MR adjusted for arsenic exposure indicated an
increased risk of BCC with short telomeres. The interaction
between arsenic exposure and telomere length on BCC risk was
statistically significant (P = 0.02). Within each tertile
based on arsenic exposure, the individuals with shorter
telomeres were at an increased risk of BCC, with highest
risk being in the highest exposed group (OR = 16.13, $95\%$
CI = 6.71-40.00, P<0.0001); followed by those in medium
exposure group and low exposure group. The combined effect
of highest arsenic exposure and shortest telomeres on BCC
risk (OR = 10.56, $95\%$ CI = 5.14-21.70) showed a
statistically significant departure from additivity
(interaction constant ratio 6.56, P = 0.03). Our results
show that in the presence of arsenic exposure, decreased
telomere length predisposes individuals to increased risk of
BCC, with the effect being synergistic in individuals with
highest arsenic exposure and shortest telomeres.},
cin = {C050 / C060 / L101},
ddc = {610},
cid = {I:(DE-He78)C050-20160331 / I:(DE-He78)C060-20160331 /
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:30874287},
doi = {10.1093/carcin/bgz059},
url = {https://inrepo02.dkfz.de/record/143386},
}