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000277925 1001_ $$00000-0001-8055-3729$$aPark, Hanla A$$b0$$eFirst author
000277925 245__ $$aGenome-wide study of genetic polymorphisms predictive for outcome from first-line oxaliplatin-based chemotherapy in colorectal cancer patients.
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000277925 500__ $$a#EA:C020#LA:C020# / 2023 Nov 1;153(9):1623-1634
000277925 520__ $$aWe conducted the first large genome-wide association study to identify novel genetic variants that predict better (or poorer) prognosis in colorectal cancer patients receiving standard first-line oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin. We used data from two phase III trials, NCCTG N0147 and NCCTG N9741 and a population-based patient cohort, DACHS. Multivariable Cox proportional hazards models were employed, including an interaction term between each SNP and type of treatment for overall survival (OS) and progression-free survival. The analysis was performed for studies individually, and the results were combined using fixed-effect meta-analyses separately for resected stage III colon cancer (3098 patients from NCCTG N0147 and 549 patients from DACHS) and mCRC (505 patients from NCCTG N9741 and 437 patients from DACHS). We further performed gene-based analysis as well as in silico bioinformatics analysis for CRC-relevant functional genomic annotation of identified loci. In stage III colon cancer patients, a locus on chr22 (rs11912167) was associated with significantly poorer OS after oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin (Pinteraction < 5 × 10-8 ). For mCRC patients, three loci on chr1 (rs1234556), chr12 (rs11052270) and chr15 (rs11858406) were found to be associated with differential OS (P < 5 × 10-7 ). The locus on chr1 located in the intronic region of RCSD1 was replicated in an independent cohort of 586 mCRC patients from ALGB/SWOG 80405 (Pinteraction = .04). The GWA gene-based analysis yielded for RCSD1 the most significant association with differential OS in mCRC (P = 6.6 × 10-6 ). With further investigation into its biological mechanisms, this finding could potentially be used to individualize first-line treatment and improve clinical outcomes.
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000277925 650_7 $$2Other$$aadjuvant chemotherapy
000277925 650_7 $$2Other$$acolorectal cancer prognosis
000277925 650_7 $$2Other$$agenome-wide association study
000277925 650_7 $$2Other$$aoxaliplatin-based treatment
000277925 650_7 $$2Other$$asingle nucleotide polymorphism
000277925 7001_ $$0P:(DE-He78)92820b4867c955a04f642707ecf35b40$$aEdelmann, Dominic$$b1$$udkfz
000277925 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b2$$udkfz
000277925 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b3$$udkfz
000277925 7001_ $$aHarrison, Tabitha A$$b4
000277925 7001_ $$aHua, Xinwei$$b5
000277925 7001_ $$aShi, Qian$$b6
000277925 7001_ $$aSilverman, Allison$$b7
000277925 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b8$$udkfz
000277925 7001_ $$0P:(DE-He78)b791a47b92809f7c54501331f72e0243$$aMacauda, Angelica$$b9$$udkfz
000277925 7001_ $$aSchneider, Martin$$b10
000277925 7001_ $$aGoldberg, Richard M$$b11
000277925 7001_ $$aAlberts, Steven R$$b12
000277925 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b13$$udkfz
000277925 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b14$$udkfz
000277925 7001_ $$aChan, Andrew T$$b15
000277925 7001_ $$aPeters, Ulrike$$b16
000277925 7001_ $$aNewcomb, Polly A$$b17
000277925 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b18$$eLast author$$udkfz
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