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@ARTICLE{Pardini:144081,
author = {B. Pardini and A. Corrado and E. Paolicchi and G. Cugliari
and S. I. Berndt and S. Bezieau and S. A. Bien and H.
Brenner$^*$ and B. J. Caan and P. T. Campbell and G. Casey
and A. T. Chan and J. Chang-Claude$^*$ and M. Cotterchio and
M. Gala and S. J. Gallinger and R. W. Haile and T. A.
Harrison and R. B. Hayes and M. Hoffmeister$^*$ and J. L.
Hopper and L. Hsu and J. Huyghe and M. A. Jenkins and L. Le
Marchand and Y. Lin and N. M. Lindor and H. Nan and P. A.
Newcomb and S. Ogino and J. D. Potter and R. E. Schoen and
M. L. Slattery and E. White and L. Vodickova and V.
Vymetalkova and P. Vodicka and F. Gemignani and U. Peters
and A. Naccarati and S. Landi},
title = {{DNA} repair and cancer in colon and rectum: novel players
in genetic susceptibility.},
journal = {International journal of cancer},
volume = {146},
number = {2},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2019-01631},
pages = {363-372},
year = {2020},
note = {146(2):363-372},
abstract = {Inter-individual differences in DNA repair systems may play
a role in modulating the individual risk of developing
colorectal cancer. To better ascertain the role of DNA
repair gene polymorphisms on colon and rectal cancer risk
individually, we evaluated 15,419 single nucleotide
polymorphisms (SNPs) within 185 DNA repair genes using GWAS
data from the Colon Cancer Family Registry (CCFR) and the
Genetics and Epidemiology of Colorectal Cancer Consortium
(GECCO), which included 8,178 colon cancer, 2,936 rectum
cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene)
was associated with colon cancer risk (p-value=3.5x10-6 )
and rs2189517 (in RAD51B) with rectal cancer risk
(p-value=5.7x10-6 ). The results had statistical
significance close to the Bonferroni corrected p-value of
5.8x10-6 . Ninety-four SNPs were significantly associated
with colorectal cancer risk after Binomial Sequential
Goodness of Fit (BSGoF) procedure and confirmed the
relevance of DNA mismatch repair (MMR) and homologous
recombination pathways for colon and rectum cancer,
respectively. Defects in MMR genes are known to be crucial
for familial form of colorectal cancer but our findings
suggest that specific genetic variations in MLH1 are
important also in the individual predisposition to sporadic
colon cancer. Other SNPs associated with the risk of colon
cancer (e.g. rs16906252 in MGMT) were found to affect mRNA
expression levels in colon transverse and therefore working
as possible cis-eQTL suggesting possible mechanisms of
carcinogenesis. This article is protected by copyright. All
rights reserved.},
cin = {C070 / C120 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31209889},
doi = {10.1002/ijc.32516},
url = {https://inrepo02.dkfz.de/record/144081},
}