Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients

Václavíková, Radka; Nordgard, Silje H.; Alnæs, Grethe I.G.; Hubackova, Miluse; Kubala, E; Kodet, Roman; Mrhalová, Marcela; Novotný, Jan; Gut, Ivan; Kristensen, Vessela N.; Souček, Pavel

doi:10.1097/fpc.0b013e3282f60a91

Cited by 24 publications

(18 citation statements)

References 39 publications

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“…This approach has already been used in our previous studies on the role of ABCB1 and NQO1 in the prognosis of breast cancer patients. 16,25 Transcript levels of NQO2 and SOD2 in this study were significantly upregulated in tumors of the mammary gland in comparison with non-neoplastic tissues. However, analysis of clinicopathological data did not reveal any significant association of NQO1, NQO2 or SOD2 transcript levels with prognostic markers or PFS.…”

Section: Cancer Geneticsmentioning

confidence: 54%

“…24 The following data on patients were retrieved from medical records: age at diagnosis, menopausal status, personal history, family history (number of relatives affected by breast cancer, ovarian cancer or other malignant diseases), stage, tumor size, histological type and grade of the tumor, expression of estrogen and progesterone receptors and PFS. Expression of estrogen and progesterone receptors was assessed according to the published procedure 25 with the commonly used 10% cut-off value. Disease progression was determined by the same technique in all the patients followed up, i.e., radiological assessment (computer tomography, abdominal ultrasonography, chest x-ray, mammography or bone scan), and clinically in case of skin metastases.…”

Section: Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

Hubackova

Václavíková

Ehrlichová

et al. 2011

Intl Journal of Cancer

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Associations of transcript levels of oxidative stress-modifying genes SOD2, SOD3, NQO1 and NQO2 and their functional single nucleotide polymorphisms (SNPs) rs4880, rs1799895, rs2536512, rs699473, rs1800566 and rs1143684 with prognosis of breast cancer patients were studied. SNPs were assessed by allelic discrimination in a cohort of 321 breast cancer patients from the Czech Republic. Transcript levels were determined by real-time polymerase chain reaction (PCR) with absolute quantification in tumor and adjacent non-neoplastic control tissues. Both genotypes and transcript levels were then compared with available clinical data on patients. Patients carrying low activity allele Leu in NQO2 rs1143684 had a greater incidence of stage 0 or I disease (i.e., better prognosis) than patients with the Phe/Phe genotype. This association was more evident in patients without expression of progesterone receptors (p 5 0.031). Patients carrying the Thr allele in SOD3 rs2536512 SNP had a significantly greater incidence of tumors expressing estrogen receptors than patients carrying the Ala/Ala genotype (p 5 0.007). SOD3 transcript level was significantly higher in grade 1 or 2 tumors than in grade 3 tumors (p 5 0.006). Patients carrying T allele in SOD3 rs699473 SNP had significantly poorer progression-free survival (PFS) than patients carrying the CC genotype (p 5 0.038). The same applied to the subgroup of patients treated by hormonal regimens (p 5 0.021). Patients carrying the high activity Ala/Ala genotype in SOD2 (rs4880) had significantly poorer PFS than Val allele carriers in the group treated by cyclophosphamide but not hormonal regimens (p 5 0.004). Our results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients and that their significance should be further characterized.Breast cancer is the most common cancer in women. In 2008, about 1,383,523 new cases of invasive breast cancer were diagnosed worldwide. 1 The necessity of treating such a large number of patients calls for efficient tools that can be used for subgrouping patients according to estimated prognosis. A different spectrum of treatment modalities with diverse mechanisms of action and adverse effects could then be offered to various prognostic groups. Besides well-established classical prognostic factors such as tumor size, nodal status, grading and expression of hormonal receptors, numerous biological molecules are under investigation as potential prognostic biomarkers in breast carcinomas.Excess of oxidative stress, mediated by reactive oxygen species, may cause cellular deregulation leading to cell apoptosis, 2 proliferation or tumor promotion. 3 Alkylation and topoisomerase poisoning present the major mechanisms of action of cyclophosphamide and anthracyclines, respectively. Oxidative stress represents an additional cytotoxic mechanism. 4,5 One of the initial molecules of oxidative stress, superoxide anion radical, is formed by the univalent reduction of triplet-state molecular oxygen. This process is mediated by e...

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Section: Cancer Geneticsmentioning

confidence: 54%

Section: Subjectsmentioning

confidence: 99%

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

Hubackova

Václavíková

Ehrlichová

et al. 2011

Intl Journal of Cancer

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“…In another study of Czech breast cancer patients, the prognostic values of the ABCB1 genotype and phenotype were assessed, including the 1236 C/T and 3435 C/T polymorphisms. The results revealed no significant correlation between ABCB1 mRNA expression levels and clinical or pathological characteristics, but the T allele homozygous as well as T allele carriers showed an increased ER-negative status compared with wild-type carriers (Vaclavikova et al, 2008). No association was found in the genotype of the 3435 C/T polymorphism (P = 0.744) or allele frequencies (P = 0.590) between breast cancer patients and controls in an Iranian population (Tatari et al, 2009).…”

Section: Discussionmentioning

confidence: 71%

“…This is the first study to simultaneously explore the association between the ABCB1 1236 C/T and 3435 C/T polymorphisms and breast cancer risk according to menopausal status and molecular subtypes. Previous reports focused on breast cancer risk, recurrence probability, and clinicopathological characteristics with different results depending on ethnic background and the study design (Vaclavikova et al, 2008;Henríquez-Hernández et al, 2009;Lu et al, 2011;Teh et al, 2011). In this study, the 3435 C/T polymorphism was associated with a 2-fold cancer increase in risk in heterozygotes for the T allele (CT) and premenopausal breast cancer cases compared to the reference group and postmenopausal breast cancer women that were T allele carriers.…”

Section: Discussionmentioning

confidence: 74%

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients

et al. 2015

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ABSTRACT. MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms ABCB1 polymorphisms in Mexican women with breast cancer and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triplenegative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

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“…27 Our observation of a higher risk for NSOC in carriers of rs1128503 T-allele is also in accord with a previous report that the T-variant significantly alters ABCB1 expression in breast tumors. 34 We speculate that fetal genotypes at ABCB1 carrying the rs1128503 T-allele are more vulnerable to NSOC, especially under situations of maternal exposure to non-genetic risk factors for NSOC such as smoking or pharmacotherapy. It is also possible rs1128503 is not a causal polymorphism but is merely in strong linkage disequilibrium with an unobserved causal SNP.…”

Section: Abcb1 Polymorphisms and Oral Clefts A Omoumi Et Almentioning

confidence: 88%

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

et al. 2013

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ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case-control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (Po0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR) ¼ 2.04; 95% confidence interval (CI) ¼ 1.42-2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case-control analysis comparing NSOC probands with controls (OR ¼ 1.58; 95% CI ¼ 1.12-2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI ¼ 1.38-2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal-maternal interface.

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Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients

Abstract: ABCB1 SNPs may affect function of P-glycoprotein by influencing the expression level and modify breast cancer prognosis.

Cited by 24 publications

References 39 publications

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

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