Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

doi:10.1016/j.clbc.2018.04.018

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…Patients with the variant T allele could potentially report more fatigue than those who carry the wild-type genotype due to a lower efflux at the blood-brain barrier (BBB) level and higher drug concentration in the brain, especially that almost all cytotoxic drugs for breast cancer are substrates of P-gp [ 35 , 36 ]. Based on this hypothesis, various studies have previously demonstrated a significant association between CRF and three gene polymorphisms in ABCB1 : c.2677G > A/T (rs2032582) in breast cancer patients receiving docetaxel [ 37 ], and c.1236C > T (rs1128503) and c.3435C > T (rs1045642) in patients with gynecologic cancers receiving paclitaxel and carboplatin [ 38 ]. However, no previous studies have identified a correlation between our studied SNP and CRF.…”

Section: Introductionmentioning

confidence: 99%

Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors

et al. 2022

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Background Cancer-related fatigue (CRF) is one of the most common and distressing complaints reported by cancer patients during chemotherapy considerably impacting all aspects of a patient’s life (physical, psychosocial, professional, and socioeconomic). The aim of this study was to assess the severity of cancer-related fatigue in a group of breast cancer patients undergoing chemotherapy and explore the association between fatigue scores and sociodemographic, clinical, biological, psychiatric, and genetic factors. Methods A cross-sectional pilot study carried out at the oncology outpatient unit of Hôtel-Dieu de France University Hospital recruited 67 breast cancer patients undergoing chemotherapy between November 2017 and June 2019 to evaluate fatigue using the EORTC QLQ-C30 scale (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire). Genotyping for seven gene polymorphisms (COMT, DRD2, OPRM1, CLOCK, PER2, CRY2, ABCB1) was performed using the Lightcycler® (Roche). Results The prevalence of fatigue was 46.3%. Multivariable analysis taking the fatigue score as the dependent variable showed that a higher number of cycles and a lower hemoglobin level were significantly associated with higher odds of exhibiting fatigue. Moreover, having at least one C allele for DRD2 SNP (vs. TT) was significantly associated with a 4.09 higher odds of expressing fatigue compared to TT patients. Finally, patients with at least one C allele for CLOCK SNP tended to display higher fatigue levels than TT patients. Conclusions Our study showed that anemic breast cancer patients with a high number of chemotherapy cycles and those carrying at least one C allele for DRD2 and CLOCK SNPs are at greater risk of exhibiting fatigue. Since no previous research has reported such genetic results, future studies are necessary to confirm our findings.

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Section: Introductionmentioning

confidence: 99%

Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors

et al. 2022

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“…In the context of breast cancer, six studies have found significant associations between rs2032582 and toxicity or response. Variant alleles are associated with decreased risk of hematological (leukopenia) and nonhematological (fever, fatigue) adverse events due to docetaxel [21][22][23] and a reduced risk of paclitaxel resistance [24]. By contrast, rs2032582 variants associated with increased toxicity risk and improved response to anthracyclines [24][25][26], suggesting substrate-specific differences in variant effects.…”

Section: Abcb1 (Mdr1 or P-gp)mentioning

confidence: 99%

“…The common silent variant rs1045642 (I1145I) has been shown to alter MDR1 function in vitro by introduction of a rare codon that alters cotranslational folding [45]. In breast cancer, the rs1045642 variant T allele is consistently associated with increased toxicity [22,36,38] and improved outcomes [24,39] for patients treated with taxanes. In contrast, the findings for anthracyclines are conflicting and remain inconclusive with reports of increased [26,32] and decreased response and outcomes [34,35] of the variant allele.…”

Section: Abcb1 (Mdr1 or P-gp)mentioning

confidence: 99%

Impact of Variants in Atp-Binding Cassette Transporters on Breast Cancer Treatment

2020

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There has been substantial interest in the impact of ATP-binding cassette (ABC) transporter variability on breast cancer drug resistance. Here, we provide a systematic review of ABC variants in breast cancer therapy. Notably, most studies used small heterogeneous cohorts and their identified associations lack statistical stringency, replication and mechanistic support. We conclude that commonly studied ABC polymorphisms are not suitable to accurately predict therapy response or toxicity in breast cancer patients and cannot guide treatment decisions. However, recent research shows that ABC transporters harbor a plethora of rare variants with individually small effect sizes, and we argue that a shift in strategy from target variant interrogation to comprehensive profiling might hold promise to drastically improve the predictive power of outcome models.

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“…Further, in the Asia Pacific epilepsy cohort, ABCC2 rs2273697 and rs3740066 polymorphisms were associated with antiepileptic drug resistance (Sha'Ari et al, 2014). It has also been observed that ABCC2 rs3740066 is significantly associated with the vomiting of docetaxel in patients with breast cancer (Jabir et al, 2018). Therefore, in this study, these three SNPs were selected for further research.…”

Section: Introductionmentioning

confidence: 97%

Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention

Chen

Chen²,

Hao³

et al. 2022

Front. Pharmacol.

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Aim: In this study, we investigated the association between ABCC2 polymorphism and clopidogrel response as well as the associated hypothetical mechanism.Methods: Chinese patients (213) with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) and received clopidogrel were recruited. Thereafter, their ADP-induced platelet inhibition rates (PAIR%) were determined via thromboelastometry. Further, the single-nucleotide polymorphisms (SNPs) of ABCC2 were genotyped using high-resolution melting curve (HRM)-PCR, while CYP2C19*2 and *3 polymorphisms were genotyped via real-time PCR.Results: The allele frequencies of ABCC2 rs717620 were 74.88 and 25.12% for the C and T alleles, respectively. Further, ABCC2 rs717620 TT carriers exhibited significantly higher PAIR% values (72.60 ± 27.69) than both CT (61.44 ± 23.65) and CC carriers (52.72 ± 21.99) (p = 0.047 and p = 0.001, respectively), and ABCC2 rs717620 CT carriers showed significantly higher mean PAIR% values than ABCC2 rs717620 CC carriers (p = 0.011). However, the PAIR% values corresponding to ABCC2 rs2273697 and ABCC2 rs3740066 carriers were not different. Additionally, CYP2C19*2 AA carriers presented significantly lower PAIR% values than CYP2C19*2 GA (p = 0.015) and GG (p = 0.003) carriers, and CYP2C19*3 GA carriers also presented significantly lower PAIR% values than CYP2C19*3 GG carriers (p = 0.041). In patients with CYP2C19 extensive metabolizers (EM), ABCC2 rs717620 TT carriers showed significantly higher PAIR% values (89.77 ± 9.73) than CT (76.76 ± 26.00) and CC carriers (74.09 ± 25.29) (p = 0.040 and p = 0.009, respectively). In patients with CYP2C19 poor metabolizers (PM), ABCC2 rs717620 CC carriers showed significantly lower PAIR% values (51.72 ± 25.78) than CT carriers (75.37 ± 23.57) (p = 0.043). Furthermore, after adjusting for confounding factors, ABCC2 rs717620 was identified as a strong predictor of clopidogrel hyperreactivity.Conclusion: We proposed a new target, ABCC2 rs717620, in the efflux pathway that affects individual responses to clopidogrel. The TT allele of ABCC2 rs717620 was also identified as an independent risk factor for clopidogrel hyperreactivity, and CYP2C19*2 and *3 showed association with an increased risk for clopidogrel resistance. Additionally, ABCC2 rs717620 may affect individual responses to clopidogrel via post-transcriptional regulation and interaction with CYP2C19. These findings provide new insights that may guide the accurate use of clopidogrel.

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Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients

Cited by 8 publications

References 43 publications

Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors

Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors

Impact of Variants in Atp-Binding Cassette Transporters on Breast Cancer Treatment

Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention

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