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Genetic variants involved in the cGAS-STING pathway predict outcome in patients with metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.
Wang, Jingyuan; Xiao, Yi; Loupakis, Fotios; Stintzing, Sebastian; Yang, Yan; Arai, Hiroyuki; Battaglin, Francesca; Kawanishi, Natsuko; Jayachandran, Priya; Soni, Shivani; Zhang, Wu; Mancao, Christoph; Cremolini, Chiara; Liu, Tianshu; Heinemann, Volker; Falcone, Alfredo; Shen, Lin; Millstein, Joshua; Lenz, Heinz-Josef.
Afiliação
  • Wang J; Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Key Laboratory of Carcinogenesis and Translational Research (Mini
  • Xiao Y; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
  • Loupakis F; Clinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
  • Stintzing S; Department of Hematology, Oncology, and Cancer Immunology (CCM), Charité - Universitaetsmedizin Berlin, Germany.
  • Yang Y; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
  • Arai H; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Battaglin F; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kawanishi N; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Jayachandran P; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Soni S; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Zhang W; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Mancao C; Oncology Biomarker Development, Genentech Inc., Basel, Switzerland.
  • Cremolini C; Department of Translational Medicine, University of Pisa, Italy.
  • Liu T; Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Heinemann V; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
  • Falcone A; Department of Translational Medicine, University of Pisa, Italy.
  • Shen L; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.
  • Millstein J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
  • Lenz HJ; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: lenz@usc.edu.
Eur J Cancer ; 172: 22-30, 2022 09.
Article em En | MEDLINE | ID: mdl-35749909
BACKGROUND: The activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer. METHODS: Genomic DNA from blood samples of patients enrolled in FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215) was genotyped using the OncoArray-500K bead chip panel. Seven selected single nucleotide polymorphisms in 3 genes (cGAS, STING and interferon B1 (IFNB1)) were analysed for the association with overall survival and progression-free survival. RESULTS: In the cetuximab cohort, patients with STING rs1131769 any T allele showed significantly shorter overall survival (36.3 versus 56.1 months) than carriers of C/C in both univariate [hazard ratio (HR) = 2.08; 95% confidence interval (CI): 1.06-4.07; P = 0.03] and multivariate (HR = 2.98; 95% CI: 1.35-6.6; P = 0.0085) analyses; patients carrying IFNB1 rs1051922 G/A and A/A genotype showed a significantly shorter progression-free survival than carriers of G/G allele in both univariate (G/A versus G/G, 10.2 versus 14.1 months, HR = 1.84; 95% CI 1.23-2.76; A/A versus G/G, 10.7 versus 14.1 months, HR = 2.19; 95% CI 0.97-4.96; P = 0.0077) and multivariate analyses (G/A versus G/G, HR = 2; 95% CI 1.22-3.3; A/A versus G/G, HR = 2.19, 95% CI 0.92-5.26, P = 0.02). These associations were not observed in the bevacizumab arm of FIRE-3 or TRIBE. CONCLUSION: These results suggest for the first time that germline polymorphisms in STING and IFNB1 genes may predict the outcomes of cetuximab-based treatment in patients with metastatic colorectal cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Retais / Neoplasias Colorretais / Neoplasias do Colo Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Eur J Cancer Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Retais / Neoplasias Colorretais / Neoplasias do Colo Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Eur J Cancer Ano de publicação: 2022 Tipo de documento: Article