Genomic Analysis of Germline Variation Associated with Survival of Patients with Colorectal Cancer Treated with Chemotherapy Plus Biologics in CALGB/SWOG 80405 (Alliance).


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 01 2021
Historique:
received: 26 05 2020
revised: 03 08 2020
accepted: 16 09 2020
pubmed: 23 9 2020
medline: 11 1 2022
entrez: 22 9 2020
Statut: ppublish

Résumé

Irinotecan/5-fluorouracil (5-FU; FOLFIRI) or oxaliplatin/5-FU (FOLFOX), combined with bevacizumab or cetuximab, are approved, first-line treatments for metastatic colorectal cancer (mCRC). We aimed at identifying germline variants associated with survival in patients with mCRC treated with these regimens in Cancer and Leukemia Group B/SWOG 80405. Patients with mCRC receiving either FOLFOX or FOLFIRI were randomized to either cetuximab or bevacizumab. DNA from peripheral blood was genotyped for approximately 700,000 SNPs. The association between SNPs and overall survival (OS) was tested in 613 patients of genetically estimated European ancestry using Cox proportional hazards models. The four most significant SNPs associated with OS were three haplotypic SNPs between microsomal glutathione S-transferase 1 ( This is the first large genome-wide association study ever conducted in patients with mCRC treated with first-line standard treatment in a randomized phase III trial. A common SNP in

Identifiants

pubmed: 32958699
pii: 1078-0432.CCR-20-2021
doi: 10.1158/1078-0432.CCR-20-2021
pmc: PMC7785628
mid: NIHMS1631836
doi:

Substances chimiques

Biological Products 0
Organoplatinum Compounds 0
Bevacizumab 2S9ZZM9Q9V
Cetuximab PQX0D8J21J
Leucovorin Q573I9DVLP
Fluorouracil U3P01618RT
Camptothecin XT3Z54Z28A

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

267-275

Subventions

Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233253
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA143237
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233373
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196171
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233327
Pays : United States

Informations de copyright

©2020 American Association for Cancer Research.

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Auteurs

Federico Innocenti (F)

Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. innocent@unc.edu.

Alexander B Sibley (AB)

Duke Cancer Institute, Duke University, Durham, North Carolina.

Sushant A Patil (SA)

Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Amy S Etheridge (AS)

Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Chen Jiang (C)

Duke Cancer Institute, Duke University, Durham, North Carolina.

Fang-Shu Ou (FS)

Alliance Statistics and Data Management Center, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Stefanie D Howell (SD)

Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Sarah J Plummer (SJ)

Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.

Graham Casey (G)

Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.

Monica M Bertagnolli (MM)

Division of Surgical Oncology, Department of Surgery, Brigham & Women's Hospital, Boston, Massachusetts.

Howard L McLeod (HL)

Taneja College of Pharmacy, University of South Florida, Tampa, Florida.

James T Auman (JT)

UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Charles D Blanke (CD)

Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.

Yoichi Furukawa (Y)

Division of Clinical Genome Research, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.

Alan P Venook (AP)

Department of Medicine, University of California at San Francisco, San Francisco, California.

Michiaki Kubo (M)

Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.

Heinz-Josef Lenz (HJ)

Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.

Joel S Parker (JS)

UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Mark J Ratain (MJ)

Department of Medicine, University of Chicago, Chicago, Illinois.

Kouros Owzar (K)

Duke Cancer Institute, Duke University, Durham, North Carolina.
Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

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Classifications MeSH