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000126839 0247_ $$2ISSN$$a1473-1150
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000126839 1001_ $$0P:(DE-He78)560b51721f3767b514947799cf29820a$$aKap, E. J.$$b0$$eFirst author$$udkfz
000126839 245__ $$aGenetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.
000126839 260__ $$aBasingstoke$$bNature Publishing Group$$c2015
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000126839 520__ $$aOxaliplatin-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.
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000126839 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000126839 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000126839 650_7 $$2NLM Chemicals$$aOrganoplatinum Compounds
000126839 650_7 $$004ZR38536J$$2NLM Chemicals$$aoxaliplatin
000126839 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, P.$$b1$$udkfz
000126839 7001_ $$aRichter, S.$$b2
000126839 7001_ $$0P:(DE-He78)0e36ebe046be3cabb1c2e282725180b9$$aScherer, D.$$b3$$udkfz
000126839 7001_ $$0P:(DE-HGF)0$$aHabermann, N.$$b4
000126839 7001_ $$aBalavarca, Y.$$b5
000126839 7001_ $$0P:(DE-He78)bbfe0ebad1e3b608bca2b49d4f86bd09$$aJansen, L.$$b6$$udkfz
000126839 7001_ $$0P:(DE-He78)7c75a9e9dc99be6d97754df93447d6a5$$aBecker, N.$$b7$$udkfz
000126839 7001_ $$aPfütze, K.$$b8
000126839 7001_ $$0P:(DE-He78)37610ef78c733753f0836ce0e41b9fda$$aPopanda, O.$$b9$$udkfz
000126839 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, M.$$b10$$udkfz
000126839 7001_ $$aUlrich, A.$$b11
000126839 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, A.$$b12$$udkfz
000126839 7001_ $$0P:(DE-HGF)0$$aUlrich, C. M.$$b13
000126839 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, B.$$b14$$udkfz
000126839 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, H.$$b15$$udkfz
000126839 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, J.$$b16$$eLast author$$udkfz
000126839 773__ $$0PERI:(DE-600)2051501-7$$a10.1038/tpj.2015.8$$gVol. 15, no. 6, p. 505 - 512$$n6$$p505 - 512$$tThe pharmacogenomics journal$$v15$$x1473-1150$$y2015
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