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Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients.

ABSTRACT: BACKGROUND: The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. METHODS: The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. RESULTS: Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 - 20.91), as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 - 826.12) when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. CONCLUSION: In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 - 20.91) in the population of interest.

SUBMITTER: Seredina TA

PROVIDER: S-EPMC3458973 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients.

Seredina Tatyana A TA Goreva Olga B OB Talaban Valeria O VO Grishanova Alevtina Yu AY Lyakhovich Vyacheslav V VV

BMC medical genetics 20120615

<h4>Background</h4>The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity.<h4>Methods</h4>The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis.<h4>Results</h4>Here, we studied the association of functionally significant variant alleles of ...[more]

PMID: 22702493

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Project description:BackgroundBreast cancer is the most common malignancy in women, and neoadjuvant chemotherapy has been recommended to the patients with locally advanced breast cancer as the initial treatments. Long non-coding RNA (lncRNA) MEG3, an identified tumor suppressor, has been implicated in the development of various cancers. However, there is no data to evaluate the effect of MEG3 polymorphisms on neoadjuvant treatment in the breast cancer.MethodsGenotyping was performed using Nanodispenser Spectro CHIP chip spotting and Mass ARRAY Compact System. Univariate and multivariate logistic regression analyses were used to analyze the associations between the MEG3 polymorphisms and the pathological complete response (pCR). The disease-free survival (DFS) was estimated by the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to calculate the hazard ratios (HRs) with a 95% confidential interval (CI).ResultsA total of 144 patients with available pretreatment blood species were enrolled in the SHPD002 clinic trial of neoadjuvant chemotherapy for breast cancer. MEG3 rs10132552 were significantly associated with good response (Adjusted OR?=?2.79, 95% CI 1.096-7.103, p?=?0.031) in dominant model. Median follow-up time was 20?months. In multiple regression analysis, rs10132552 TC?+?CC (adjusted HR?=?0.127, 95% CI 0.22-0.728, p?=?0.02) and rs941576 AG?+?GG (adjusted HR?=?0.183, 95% CI 0.041-0.807, p?=?0.025) were significantly associated with good DFS. MEG3 rs7158663 (OR?=?0.377, 95% CI 0.155-0.917, p?=?0.032) were associated with a low risk of hemoglobin decrease in dominant models.ConclusionsLncRNA MEG3 polymorphisms were associated with the chemotherapy response and toxicity of paclitaxel and cisplatin. The result indicates that MEG3 polymorphisms can be considered as the predictive and prognostic markers for the breast cancer patients.Trial registrationRetrospectively registered (ClinicalTrials. Gov identifier: NCT02221999 ); date of registration: Aug 20th, 2014.

Project description:BackgroundOur previous study illustrated the predictive value of serum gamma-glutamyl transpeptidase (GGT) for neoadjuvant chemotherapy (NAC) sensitivity in breast cancer patients. In this study we aim to determine whether single nucleotide polymorphisms (SNPs) in the gamma-glutamyltransferase 1 (GGT1) gene are related to the NAC response and adverse events and to find out a genetic marker in predicting NAC sensitivity.MethodsThree SNP loci (rs8135987, rs5751901, rs2017869) of GGT1 gene were selected and tested among breast cancer patients reciving NAC. Four genotype models were used in SNP analysis: co-dominant model compared AA vs. Aa vs. aa; dominant model compared AA vs. Aa + aa; recessive model compared AA + Aa vs. aa; over-dominant model compared AA + aa vs. Aa. Chi-squared test and multivariable logistic regression analysis were performed between SNP genotypes, haplotypes and pathological complete response(pCR), adverse events as well as serum GGT level.ResultsA total of 143 patients were included in the study. For SNP rs8135987 (T > C), the TC genotype in over-dominant model was inversely related with pCR (adjusted OR = 0.30, 95% CI 0.10-0.88, p = 0.029) as well as the risk of peripheral neuropathy (adjusted OR = 0.39, 95% CI 0.15-0.96, p = 0.042). The TC genotype in dominant model was significantly associated with elevated serum GGT level (OR = 3.11, 95% CI 1.07-9.02, p = 0.036). For rs2017869 (G > C), the occurrence of grade 2 or greater neutropenia (OR = 0.39, 95% CI 0.08-0.84, p = 0.025) and leukopenia (OR = 0.24, 95% CI 0.08-0.78, p = 0.017) were both significantly reduced in patients with CC genotypes. For rs5751901(T > C), the CC genotype could significantly reduce the risk of grade 2 or greater neutropenia (OR = 0.29, 95% CI 0.09-0.96, p = 0.036) and leukopenia (OR = 0.27, 95% CI 0.09-0.84, p = 0.024) in recessive model.ConclusionsThe GGT1 gene SNPs might be an independent risk factor for poor response of NAC in breast cancer patients, providng theoretical basis for further precision therapy.

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Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients.

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Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients.

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