Prognostic Effect of Adenosine-related Genetic Variants in Metastatic Colorectal Cancer Treated With Bevacizumab-based Chemotherapy.

Tokunaga, Ryuma; Cao, Shu; Naseem, Madiha; Lo, Jae Ho; Battaglin, Francesca; Puccini, Alberto; Berger, Martin Dave; Soni, Shivani; Millstein, Joshua; Zhang, Wu; Stintzing, Sebastian; Loupakis, Fotios; Cremolini, Chiara; Heinemann, Volker; Falcone, Alfredo; Lenz, Heinz-Josef (2019). Prognostic Effect of Adenosine-related Genetic Variants in Metastatic Colorectal Cancer Treated With Bevacizumab-based Chemotherapy. Clinical colorectal cancer, 18(1), e8-e19. Elsevier 10.1016/j.clcc.2018.09.003

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BACKGROUND Adenosine has an immunosuppressive and angiogenic modulation of the tumor microenvironment. The present study explored the efficacy of single nucleotide polymorphisms (SNPs) in adenosine-related molecules for patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. PATIENTS AND METHODS We analyzed genomic DNA extracted from 451 samples from 3 independent cohorts: a discovery cohort of 107 patients treated with FOLFIRI (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab in FIRE-3 (ClinicalTrials.gov identifier, NCT00433927); a validation cohort of 215 patients with FOLFIRI plus bevacizumab in TRIBE (ClinicalTrials.gov identifier, NCT00719797); and a control cohort of 129 patients treated with FOLFIRI plus cetuximab in FIRE-3. The relationship between the selected SNPs and clinical outcomes was analyzed. RESULTS In the discovery cohort, patients with any C allele in CD39 rs11188513 had significantly shorter median progression-free survival compared with those with the T/T variant (11.3 vs. 13.1 months; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .022) on univariate analysis. Also, their overall survival (OS) was shorter (27.4 vs. 49.9 months; HR, 2.10; 95% CI, 1.07-4.10; P = .031) on univariate and multivariable analyses. The significant association between CD39 rs11188513 and OS was confirmed in the validation cohort (25.8 vs. 31.6 months; HR, 1.53; 95% CI, 1.09-2.15; P = .013). CD73 rs2229523 and A2BR rs2015353 in the discovery cohort and CD39 rs2226163 in the validation cohort showed significant correlations with OS on univariate and multivariable analyses. None of SNPs were significant in the cetuximab control cohort. CONCLUSION Selected SNPs in the adenosine pathway could affect the clinical outcomes of patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Berger, Martin Dave

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1938-0674

Publisher:

Elsevier

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

28 Feb 2019 15:04

Last Modified:

24 Oct 2019 19:20

Publisher DOI:

10.1016/j.clcc.2018.09.003

PubMed ID:

30293873

Uncontrolled Keywords:

A2AR CD39 CD73 SNP mCRC

BORIS DOI:

10.7892/boris.124090

URI:

https://boris.unibe.ch/id/eprint/124090

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