Journal Article

DKFZ-2017-02867

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.

Kap, E. J. (First author)DKFZ* ; Seibold, P.DKFZ* ; Richter, S. ; Scherer, D.DKFZ* ; Habermann, N.DKFZ* ; Balavarca, Y. ; Jansen, L.DKFZ* ; Becker, N.DKFZ* ; Pfütze, K. ; Popanda, O.DKFZ* ; Hoffmeister, M.DKFZ* ; Ulrich, A. ; Benner, A.DKFZ* ; Ulrich, C. M.DKFZ* ; Burwinkel, B.DKFZ* ; Brenner, H.DKFZ* ; Chang-Claude, J. (Last author)DKFZ*

2015
Nature Publishing Group Basingstoke

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Please use a persistent id in citations: doi:10.1038/tpj.2015.8

Abstract: Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.

Keyword(s): Biomarkers, Tumor ; DNA-Binding Proteins ; Organoplatinum Compounds ; oxaliplatin

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Contributing Institute(s):

1. Epidemiologie von Krebserkrankungen (C020)
2. Präventive Onkologie (G110)
3. Klinische Epidemiologie und Alternsforschung (C070)
4. Biostatistik (C060)
5. Epigenomik und Krebsrisikofaktoren (C010)
6. Molekulare Epidemiologie (C080)
7. DKTK Heidelberg (L101)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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