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@ARTICLE{Park:277925,
author = {H. A. Park$^*$ and D. Edelmann$^*$ and F. Canzian$^*$ and
P. Seibold$^*$ and T. A. Harrison and X. Hua and Q. Shi and
A. Silverman and A. Benner$^*$ and A. Macauda$^*$ and M.
Schneider and R. M. Goldberg and S. R. Alberts and M.
Hoffmeister$^*$ and H. Brenner$^*$ and A. T. Chan and U.
Peters and P. A. Newcomb and J. Chang-Claude$^*$},
title = {{G}enome-wide study of genetic polymorphisms predictive for
outcome from first-line oxaliplatin-based chemotherapy in
colorectal cancer patients.},
journal = {International journal of cancer},
volume = {153},
number = {9},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2023-01581},
pages = {1623-1634},
year = {2023},
note = {#EA:C020#LA:C020# / 2023 Nov 1;153(9):1623-1634},
abstract = {We conducted the first large genome-wide association study
to identify novel genetic variants that predict better (or
poorer) prognosis in colorectal cancer patients receiving
standard first-line oxaliplatin-based chemotherapy vs
chemotherapy without oxaliplatin. We used data from two
phase III trials, NCCTG N0147 and NCCTG N9741 and a
population-based patient cohort, DACHS. Multivariable Cox
proportional hazards models were employed, including an
interaction term between each SNP and type of treatment for
overall survival (OS) and progression-free survival. The
analysis was performed for studies individually, and the
results were combined using fixed-effect meta-analyses
separately for resected stage III colon cancer (3098
patients from NCCTG N0147 and 549 patients from DACHS) and
mCRC (505 patients from NCCTG N9741 and 437 patients from
DACHS). We further performed gene-based analysis as well as
in silico bioinformatics analysis for CRC-relevant
functional genomic annotation of identified loci. In stage
III colon cancer patients, a locus on chr22 (rs11912167) was
associated with significantly poorer OS after
oxaliplatin-based chemotherapy vs chemotherapy without
oxaliplatin (Pinteraction < 5 × 10-8 ). For mCRC patients,
three loci on chr1 (rs1234556), chr12 (rs11052270) and chr15
(rs11858406) were found to be associated with differential
OS (P < 5 × 10-7 ). The locus on chr1 located in the
intronic region of RCSD1 was replicated in an independent
cohort of 586 mCRC patients from ALGB/SWOG 80405
(Pinteraction = .04). The GWA gene-based analysis yielded
for RCSD1 the most significant association with differential
OS in mCRC (P = 6.6 × 10-6 ). With further investigation
into its biological mechanisms, this finding could
potentially be used to individualize first-line treatment
and improve clinical outcomes.},
keywords = {adjuvant chemotherapy (Other) / colorectal cancer prognosis
(Other) / genome-wide association study (Other) /
oxaliplatin-based treatment (Other) / single nucleotide
polymorphism (Other)},
cin = {C020 / C060 / C055 / C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)C055-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37539667},
doi = {10.1002/ijc.34663},
url = {https://inrepo02.dkfz.de/record/277925},
}