Journal Article

DKFZ-2021-02807

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Validation of genetic markers associated with survival in colorectal cancer patients treated with oxaliplatin-based chemotherapy.

Park, H. A. (First author)DKFZ* ; Seibold, P.DKFZ* ; Edelmann, D.DKFZ* ; Benner, A.DKFZ* ; Canzian, F.DKFZ* ; Alwers, E.DKFZ* ; Jansen, L.DKFZ* ; Schneider, M. ; Hoffmeister, M.DKFZ* ; Brenner, H.DKFZ* ; Chang-Claude, J. (Last author)DKFZ*

2022
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-21-0814

Abstract: Associations between candidate genetic variants and treatment outcomes of oxaliplatin, a drug commonly used for colorectal cancer patients, have been reported but not robustly established. This study aimed to validate previously reported prognostic and predictive genetic markers for oxaliplatin treatment outcomes and evaluate additional putative functional variants.Fifty-three SNPs were selected based on previous reports (40 SNPs) or putative function in candidate genes (13 SNPs). We used data from 1,502 stage II-IV colorectal cancer patients who received primary adjuvant chemotherapy, 37% of whom received oxaliplatin treatment. Multivariable Cox proportional hazards models for overall survival and progression-free survival were applied separately in stage II-III and stage IV patients. For predictive SNPs, differential outcomes according to the type of chemotherapy (oxaliplatin-based vs. others) were evaluated using an interaction term. For prognostic SNPs, the association was assessed solely in patients with oxaliplatin-based treatment.Twelve SNPs were predictive and/or prognostic at P<0.05 with differential survival based on the type of treatment, in stage II-III patients (GSTM5-rs11807, ERCC2-rs13181, ERCC2-rs1799793, ERCC5-rs2016073, XPC-rs2228000, P2RX7-rs208294, HMGB1-rs1360485) and in stage IV patients (GSTM5-rs11807, MNAT1-rs3783819, MNAT1-rs4151330, CXCR1-rs2234671, VEGFA-rs833061, P2RX7-rs2234671). Additionally, five novel putative functional SNPs were identified to be predictive (ATP8B3-rs7250872, P2RX7-rs2230911, RPA1-rs5030755, MGMT-rs12917, P2RX7-rs2227963).Some SNPs yielded prognostic and/or predictive associations significant at P<0.05, however, none of the associations remained significant after correction for multiple testing.We did not robustly confirm previously reported SNPs despite some suggestive findings but identified further potential predictive SNPs, which warrant further investigation in well-powered studies.

Note: #EA:C020#LA:C020# / 2022 Feb;31(2):352-361

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C060 Biostatistik (C060)
3. C055 Genomische Epidemiologie (C055)
4. C070 Klinische Epidemiologie und Alternf. (C070)
5. M110 Epidemiologisches Krebsregister Baden-Württemberg (M110)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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