Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan

Abuhaliema, Ali; Yousef, Al-Motassem; Elmadany, Nirmeen; Bulatova, Nailya; Awwad, Nemah M; Yousef, Muhammad; Majdalawi, Khalil Z Al

doi:10.7314/apjcp.2016.17.1.261

Cited by 20 publications

(20 citation statements)

References 34 publications

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“…Counterwise, a recent study of Abouhalima et al [26] among Jordanian women have revealed a higher prevalence of CC genotype in breast cancer patients compared to controls ( P < 0.001) and individuals with T allele were 2 times less likely to develop breast cancer ( P < 0.0001). It should be noted that in a study of Salem et al, the T allele was more prevalent among Jordanians than the C allele [33].…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that in a study of Salem et al, the T allele was more prevalent among Jordanians than the C allele [33]. On the other hand, the authors suggested strong linkage disequilibrium with other polymorphisms in ABCB1 gene and alterations in the post translational pathway which influences the efficacy and stability of P-gp in patients with CC genotype [26]. Similarly, in Kurdish patients the frequency of CC genotype and C allele were higher in patients than in controls; this result was not statistically significant [25].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have investigated the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in different populations, however the results are inconsistent and the relevance of this polymorphism remains confusing [12–26]. …”

Section: Introductionmentioning

confidence: 99%

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Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis

et al. 2016

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BackgroundBreast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population.MethodsA case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed.ResultsGenotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767–1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973–1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972–1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145–1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001–1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220–3.371; P = 0.006).ConclusionsWe have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis

et al. 2016

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“…A haplotype analysis within ABCB1 performed, i.a., in neoplastic and neurological diseases turned out to be a useful tool in terms of evaluation of the morbidity and the effectiveness of treatment [2, 4, 20, 22, 23, 27, 42, 43, 45]. …”

Section: Discussionmentioning

confidence: 99%

Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T (rs1045642) in patients with bullous pemphigoid

et al. 2018

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Bullous pemphigoid (BP) constitutes the most prevalent disease in the group of bullous dermatoses with the autoimmune background. Some authors suggest that certain cytokines (IL-2, IFN-γ) may be transported by P-glycoprotein (P-gp), the product of the ABCB1 gene. ABCB1 polymorphism might affect not only the effectiveness of treatment with drugs that are P-gp substrates but also contribute to the development of diseases, including BP. In the present work, we resolved to conduct a haplotype analysis of ABCB1 in patients with BP and to answer the question of whether any of the haplotypes are able to affect the incidence of this entity. The study involved 71 patients with BP and 100 healthy volunteers. Determination of polymorphisms 1236C > T and 3435C > T in ABCB1 was carried out with the PCR–RFLP (Polymerase Chain Reaction–Restriction Fragment Length Polymorphism) method. The 2677G > T/A ABCB1 polymorphism was analyzed with the allele-specific PCR method. It was observed that the 1236T-2677G-3435T haplotype occurred with a statistically significantly lower frequency in patients with BP than in controls (1.4 vs. 10.0%). Carriers of this haplotype were also shown to have had a low relative risk for BP (OR = 0.13, p = 0.003). Haplotype analysis of ABCB1 conducted in patients with BP demonstrated that the 1236T-2677G-3435T haplotype may protect against development of this entity.

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“…The C3435T polymorphism has been studied foremost in the context of statin use in patients with hypercholesterolemia and vascular disease, but the results have been somewhat inconsistent in terms of both effectiveness and treatment side effects, Table 1 ; ( 12 , 14 , 18 – 20 , 27 – 33 ). The T-allele has been linked to an increased breast cancer risk in two small studies ( 34 , 35 ) and possibly to different patient responses to chemotherapeutic agents, tamoxifen, and trastuzumab ( 24 ). While a recent large genome wide association study did not identify this SNP as an independent breast cancer risk modifier ( 36 ), another recent genome wide association study identified the candidate gene ABCB1 as a possible effect modifier of statins on breast cancer risk in postmenopausal women via another SNP (rs9282564) near ABCB1 ( 37 ).…”

Section: Introductionmentioning

confidence: 99%

Interactions Between ABCB1 Genotype and Preoperative Statin Use Impact Clinical Outcomes Among Breast Cancer Patients

et al. 2018

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Multiple clinical trials investigate statins' effects in breast cancer. The ABCB1 genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, ABCB1 genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, ABCB1 C3435T genotype, and HMGCR expression in relation to outcome were analyzed in 985 primary breast cancer patients from a population-based prospective cohort in Sweden from 2002 to 2012. Preoperative statin use (n = 80) was not associated with ABCB1 C3435T genotype (n = 576), HMGCR expression (n = 848), or clinical outcomes. ABCB1 C3435T TT-carriers had lower risk of breast cancer events than any C-carriers (adjusted hazard ratio (HRadj) 0.74; 95%CI 0.49, 1.12), but only in non-statin users (Pinteraction = 0.042). Statin users with TT genotype had higher risk of distant metastasis (HRadj 4.37; 95%CI 1.20, 15.91; Pinteraction = 0.009) and shorter overall survival than other patients (HRadj 3.77; 95%CI 1.37, 10.39; Pinteraction = 0.019). In conclusion, there were nominally significant interactions between ABCB1 genotype and preoperative statin use on clinical outcomes, while preoperative statin use was not associated with outcomes. Since this is an exploratory study of the impact of the ABCB1 genotype in relation to statin use and clinical outcomes in the breast cancer setting, the results should be interpreted with caution and warrant replication in an independent cohort, preferably in a randomized setting. Since statin use is common in breast cancer patients, it would be of interest to further elucidate the clinical impact of the ABCB1 genotype in breast cancer.

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Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan

Cited by 20 publications

References 34 publications

Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis

Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis

Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T (rs1045642) in patients with bullous pemphigoid

Interactions Between ABCB1 Genotype and Preoperative Statin Use Impact Clinical Outcomes Among Breast Cancer Patients

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