Trial reportThe pharmacogenomics journal2014
Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer.
Open access · bronzeAbstract readClinical Trial, Phase III
In one paragraph
Trial report in The pharmacogenomics journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- SNP's use as a potential chemotoxicity stratification tool in breast cancer: from bench to clinic.Functional & integrative genomics · 2025Review
- Pharmacogenetics as a Future Tool to Risk-Stratify Breast Cancer Patients According to Chemotoxicity Potential from the Doxorubicin Hydrochloride and Cyclophosphamide (AC) Regimen.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pharmacogenomics of antibiotic-induced hypersensitivity reactions: current evidence and implications in clinical practice.Frontiers in pharmacology · 2025Review
- Precision medicine on a budget in Africa: using existing genetic data to mitigate adverse drug reactions to conventional cancer drugs.Frontiers in bioinformatics · 2025Article
- Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.Cancer chemotherapy and pharmacology · 2024Article
- Pharmacogenetics of Drug Metabolism: The Role of Gene Polymorphism in the Regulation of Doxorubicin Safety and Efficacy.Cancers · 2022Review
- Role of Genetic Polymorphisms in Drug-Metabolizing Enzyme-Mediated Toxicity and Pharmacokinetic Resistance to Anti-Cancer Agents: A Review on the Pharmacogenomics Aspect.Clinical pharmacokinetics · 2022Review
- Lack of association of CYP2B6 pharmacogenetics with cyclophosphamide toxicity in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
- Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy.Journal of personalized medicine · 2022Article
- The Relation of Haplotype ATP-binding Cassette B1 and Glutathione S-transferase P1Oman medical journal · 2022Article
- How to conjugate the stemness marker ALDH1A1 with tumor angiogenesis, progression, and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy.Frontiers in pharmacology · 2020Review
- rs3764435 Associated With Parkinson's Disease in Mexican Mestizos: Case-Control Study Reveals Protective Effects Against Disease Development and Cognitive Impairment.Frontiers in neurology · 2019Article
- The role of solute carrier (SLC) transporters in actinomycin D pharmacokinetics in paediatric cancer patients.European journal of clinical pharmacology · 2018Article
- Genetic background influences susceptibility to chemotherapy-induced hematotoxicity.The pharmacogenomics journal · 2018Article
- Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients.Oncotarget · 2018Article
- Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment.Pharmacogenomics and personalized medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 10 institutions in 1 country.
S YaoDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
L E SuchestonDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
H ZhaoDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
W E BarlowSWOG Statistical Center, Seattle, WA, USA.
G ZirpoliDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
S LiuDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
H C F MooreDepartment of Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, USA.
G Thomas BuddDepartment of Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, USA.
D L HershmanColumbia University Medical Center, Columbia University, New York, NY, USA.
W DavisDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
G L CiupakDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
J A StewartDepartment of medicine, Baystate Medical Center, Springfield, MA, USA.
C IsaacsLombardi Comprehensive Cancer Center, Washington, DC, USA.
T J HobdayMayo Clinic, Rochester, MN, USA.
M SalimAllan Blair Cancer Centre, Regina, SK, Canada.
G N HortobagyiDepartment of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
J R GralowSeattle Cancer Care Alliance, Seattle, WA, USA.
R B LivingstonCollege of Medicine, Arizona Cancer Center, Tucson, AZ, USA.
K S AlbainLoyola University Chicago Cardinal Bernardin Cancer Center, Maywood, IL, USA.
D F HayesDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
C B AmbrosoneDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
Roswell Park Comprehensive Cancer Center · USCleveland Clinic · USThe University of Texas MD Anderson Cancer Center · USCancer Research And Biostatistics · USColumbia University Irving Medical Center · USLoyola University Chicago · USMayo Clinic in Arizona · USSeattle Cancer Care Alliance · USUniversity of Michigan–Ann Arbor · USVince Lombardi Cancer Clinic · US
Funding
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1MSWOG - Foreign Accrual under UMiU10CA032102 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BLANKE, CHARLES D. · 1985 to 2013
$141.3MECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6MTwo-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6MSWOG Statistics & Data Management Center complex - extension supplement for GY06U10CA180819 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Catherine M. Tangen · 2014 to 2026
$115.2MTRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0MSOUTHWEST ONCOLOGY GROUP--STATISTICAL CENTERU10CA038926 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI LEBLANC, MICHAEL L. · 1985 to 2013
$69.8MSOUTHEAST CANCER CONTROL COSORTIUM, INCU10CA045808 · NCI · SOUTHEAST CLINICAL ONCOL RES CONSORTIUM · PI ATKINS, JAMES NORMAN · 1987 to 2013
$26.6MCOMMUNITY CLINICAL ONCOLOGY PROGRAMU10CA035431 · NCI · VIA CHRISTI REGIONAL MEDICAL CENTER · PI DAKHIL, SHAKER R · 1985 to 2014
$24.0MUPSTATE CAROLINA COMMUNITY CLINICAL ONCOLOGY PROGRAMU10CA035119 · NCI · SPARTANBURG REGIONAL MEDICAL CENTER · PI BEARDEN, JAMES D · 1985 to 2013
$21.5MMICHIGAN CANCER RESEARCH CONSORTIUM CCOPU10CA063848 · NCI · SAINT JOSEPH MERCY HEALTH SYSTEM · PI STELLA, PHILIP J · 1994 to 2014
$17.2MGRAND RAPIDS CLINICAL ONCOLOGY PROGRAMU10CA035178 · NCI · SPECTRUM HEALTH HOSPITALS · PI PADULA, GILBERT DARIN ANTHONY · 1985 to 2014
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Abstract
Hematological and gastrointestinal toxicities are common among patients treated with cyclophosphamide and doxorubicin for breast cancer. To examine whether single-nucleotide polymorphisms (SNPs) in key pharmacokinetic genes were associated with risk of hematological or gastrointestinal toxicity, we analyzed 78 SNPs in ABCB1, ABCC1 and ALDH1A1 in 882 breast cancer patients enrolled in the SWOG trial S0221 and treated with cyclophosphamide and doxorubicin. A two-SNP haplotype in ALDH1A1 was associated with an increased risk of grade 3 and 4 hematological toxicity (odds ratio=1.44, 95% confidence interval=1.16-1.78), which remained significant after correction for multiple comparisons. In addition, four SNPs in ABCC1 were associated with gastrointestinal toxicity. Our findings provide evidence that SNPs in pharmacokinetic genes may have an impact on the development of chemotherapy-related toxicities. This is a necessary first step toward building a clinical tool that will help assess risk of adverse outcomes before undergoing chemotherapy.
Indexed as
Aldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAntineoplastic Combined Chemotherapy ProtocolsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BBreast NeoplasmsCyclophosphamideDoxorubicinFemaleHumansPolymorphism, Single NucleotideRetinal DehydrogenaseABCB1 protein, humanAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BCyclophosphamideDoxorubicinmultidrug resistance-associated protein 1Retinal Dehydrogenase
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