Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer

Haroun, Faysal; Al-Shaar, Laila; Habib, Robert H.; El-Saghir, Nagi S.; Tfayli, Arafat; Bazarbachi, Ali; Salem, Ziad; Shamseddine, A.; Taher, Alì; Cascorbi, Ingolf; Zgheib, Nathalie K.

doi:10.1007/s00280-014-2632-4

Cited by 23 publications

(13 citation statements)

References 25 publications

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“…To further improve outcomes, the development of specific therapeutic protocols based on individuals’ genetic profiles is essential. Moreover, genetic polymorphisms were shown to affect neutrophil counts in patients who are administered DOX-based chemotherapy [22]; in these studies, the emergence of chemotherapy-induced severe toxicities was more frequent in Asian patients than in Western patients, suggesting that the former are more susceptible to febrile neutropenia.…”

Section: Discussionmentioning

confidence: 99%

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients

et al. 2016

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Breast cancer is the most common cancer in women worldwide. Doxorubicin-based chemotherapy is used to treat breast cancer patients; however, neutropenia is a common hematologic side effect and can be life-threatening. The ABCB1 and SLC22A16 genes encode proteins that are essential for doxorubicin transport. In this study, we explored the effect of 2 common polymorphisms in ABCB1 (rs10276036 C/T) and SLC22A16 (rs12210538 A/G) on the development of grade 3/4 febrile neutropenia in Iranian breast cancer patients. Our results showed no significant association between these polymorphisms and grade 3/4 febrile neutropenia; however, allele C of ABCB1 (rs10276036 C/T) (p = 0.315, OR = 1.500, 95% CI = 0.679–3.312) and allele A of SLC22A16 (rs12210538 A/G) (p = 0.110, OR = 2.984, 95% CI = 0.743–11.988) tended to have a greater association with grade 3/4 febrile neutropenia, whereas allele T of ABCB1 (rs10276036) (p = 0.130, OR = 0.515, 95% CI = 0.217–1.223) and allele G of SLC22A16 (rs12210538) (p = 0.548, OR = 0.786, 95% CI = 0.358–1.726) tended to protect against this condition. In addition to breast cancer, a statistically significant association was also observed between the development of grade 3/4 febrile neutropenia and other clinical manifestations such as stage IIIC cancer (p = 0.037) and other diseases (p = 0.026). Our results indicate that evaluation of the risk of grade 3/4 neutropenia development and consideration of molecular and clinical findings may be of value when screening for high-risk breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients

et al. 2016

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“…A study of CYP2B6 haplotypes in 38 breast cancer patients found a significant gene‐dose relationship and time to relapse, while no association was observed with outcomes and CYP2B6 haplotypes in a larger cohort of breast cancer patients ( n = 350) . However, although this study did not assess CYP2C19 , disease‐free survival was associated ( P = 0.02, unadjusted) with CYP3A4*1B .…”

Section: Therapeutic Outcomesmentioning

confidence: 57%

The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes

Helsby

Yong

Kan

et al. 2019

Brit J Clinical Pharma

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Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene–gene interactions to confirm these findings and may allow personalised treatment regimens.

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“…CYP2B6*6 was found to have a protective effect from high grades neutropenia (Tsuji et al, 2016). However, the same haplotype, determined by rs3745274, did not show any significant association when the need for dose reduction, erythropoietin use, transfusion, or iron supplementation was considered as the studied outcomes (Haroun et al, 2015).…”

Section: Slco1b3 Cyp2c8 Abcb1mentioning

confidence: 89%

Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy

2020

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Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse events occurring in variable frequencies. These events can be a significant barrier in completing the treatment regimens. Germline genomic variants are thought of as potential determinants in chemotherapy response and the development of side effects. Some pharmacogenomic studies were designed to explore germline variants that can be used as biomarkers for predicting developing toxicity or adverse events during chemotherapy in BC. In this review, we reassess and summarize the major findings of pharmacogenomic studies of chemotherapy toxicity during BC management. In addition, deficiencies hampering utilizing these findings and the potential targets of future research are emphasized. Main insufficiencies in toxicity pharmacogenomics studies originate from study design, sample limitations, heterogeneity of selected genes, variants, and toxicity definitions. With the advent of high throughput genotyping techniques, researchers are expected to explore the identified as well as the potential genetic biomarkers of toxicity and efficacy to improve BC management. However, to achieve this, the limitations of previous work should be evaluated and avoided to reach more conclusive and translatable evidence for personalizing BC chemotherapy.

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Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer

Cited by 23 publications

References 25 publications

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients

The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes

Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy

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