The associations of genetic polymorphisms in<i>CYP1A2</i>and<i>CYP3A4</i>with clinical outcomes of breast cancer patients in northern China

Bai, Xianan; Xie, Jingjing; Sun, Shanshan; Zhang, Xianyu; Jiang, Yongdong; Pang, Da

doi:10.18632/oncotarget.16359

Cited by 14 publications

(20 citation statements)

References 30 publications

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“…On the other hand, we cannot confirm the previously reported association between this SNP and the age of onset of mammary tumours, which may be related to differences in the cohort populations and to the small representativeness of this SNP, accounting for only 23.7% of the animals included in the present study. OS of breast cancer 33,34. Data from the present investigation identified COMT haplotypes with apparently opposite effects regarding CMTs progression, reinforcing the role of hormonal factors as prognosticators in this type of neoplasm.…”

supporting

confidence: 71%

“…Our results emphasize the importance of genetic variation in estrogens metabolic pathways as prognosticators in both human and canine mammary neoplasia. Recently, some investigators described an association between genetic SNP in Cytochrome P450 (CYP) enzymes (involved in estrogens biosynthesis) and the patients' age, tumour size, histological grade and OS of breast cancer . Data from the present investigation identified COMT haplotypes with apparently opposite effects regarding CMTs progression, reinforcing the role of hormonal factors as prognosticators in this type of neoplasm.…”

Section: Discussionmentioning

confidence: 99%

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Catechol‐o‐methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours

Canadas

Santos

Pinto

et al. 2018

Vet Comparative Oncology

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The enzyme catechol-o-methyltransferase (COMT) is responsible for inactivation of catechol estrogens, which are well-recognized carcinogenic metabolites. Two single-nucleotide polymorphisms (SNPs) in canine COMT gene were previously associated with the age of onset of mammary tumours and with the clinical progression of the disease. However, no information is available regarding the impact of other known SNPs in COMT gene in canine mammary tumours. The aim of the present study is to evaluate the influence of COMT SNP in clinicopathological features and outcome of canine mammary tumours. A case series study was conducted involving 155 non-neutered bitches with mammary tumours submitted to follow-up for 24 months after surgery. Three genotypes were considered: Genotype 1 (rs853046495); Genotype 2 (rs23350589, rs23322686, rs23336579, and rs852564758); Genotype 3 (rs851328636 and rs853133060). Genotype 1 was associated to low degree of tubular differentiation. Genotype 2 was related to the development of intermediate/high-histological-grade carcinomas and to vascular invasion. Genotype 3 was associated to reduced nuclear pleomorphism and well-differentiated carcinomas. Data from the present investigation allowed the identification of COMT genetic profiles associated with pathological features of mammary tumours that constitute relevant prognostic factors. The assessment of the COMT genotypes may represent a helpful tool in the clinical management of canine mammary tumours, assisting in the selection of individualized preventive and therapeutic strategies, according to the animals' genetic profile.

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supporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Catechol‐o‐methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours

Canadas

Santos

Pinto

et al. 2018

Vet Comparative Oncology

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“…A GWAS study in Chinese Han illustrated that rs3751599 is a human height-related SNP in CYP19A1 locus [ 25 ]. CYP1A2 rs2470890 polymorphisms have been studied in breast cancer of northern China, and in depression of Chinese Han, as well as in pharmacogenomics analysis among Chinese [ 26 – 28 ]. However, neither of these two SNPs were investigated in T2DM, and this is the first study to carry out the data-based association analysis and found their protective effects on T2DM in certain populations.…”

Section: Discussionmentioning

confidence: 99%

Association of CYP19A1 and CYP1A2 genetic polymorphisms with type 2 diabetes mellitus risk in the Chinese Han population

Yang

Wang

2020

Lipids Health Dis

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Background: Type 2 diabetes mellitus (T2DM), one of the global health issues, is a group of metabolic diseases and is affected by several genetic loci in the clinical phenotype. This study intended to ascertain associations between CYP19A1 and CYP1A2 gene polymorphisms with the T2DM risk in Chinese Han. Methods: Seven single nucleotide polymorphisms (SNPs) in total including five of CYP19A1 (rs4646, rs6493487, rs1062033, rs17601876 and rs3751599) and two of CYP1A2 (rs762551 and rs2470890) from 512 T2DM patients and 515 non-diabetic controls were genotyped in the platform of Agena MassARRAY. SPSS 18.0 was utilized for analyzing genotyping results. Logistic regression models were conducted for the risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). Results: The results suggested a significant association between genotype GC of rs1062033 with a decreased T2DM risk (OR = 0.73, 95% CI = 0.55-0.96, P = 0.025) under the co-dominant (heterozygous) model. The results of stratification analysis with age and gender adjustment revealed that the effects of all selected SNPs in CYP19A1 and CYP1A2 on the T2DM susceptibility were dependent on age, body mass index (BMI) and disease progression (P < 0.05). The haplotype analysis was further conducted and the results indicated that C rs1062033 G rs17601876 A rs3751599 in CYP19A1 played a protective role (OR = 0.48, 95% CI = 0.25-0.91, P = 0.026) in T2DM patients with diabetic retinopathy. Conclusion: This population-based case-control study suggested that CYP19A1 and CYP1A2 variations might affect the susceptibility of T2DM. The findings provide a theoretical basis for searching the clinical therapeutic markers and attractive drug targets of T2DM.

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“…In the study, we investigated whether these SNPs had any impact on cinacalcet response in healthy Chinese subjects after receiving a single dose under fasting conditions. We selected SNPs of CYP3A4, CYP2D6, and CYP1A2 enzymes, which are commonly reported to affect the metabolism of other drugs, to explore whether they have any effect on the PK of cinacalcet under fasting conditions (28)(29)(30)(31)(32). We present the following article in accordance with the CONSORT reporting checklist (available at http://dx.doi.org/10.21037/atm-20-1329).…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects

et al. 2020

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Background: Our study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial. Methods: We investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet. Plasma cinacalcet concentrations were analyzed using a validated HPLC-MS/MS assay. Clinical laboratory tests evaluated safety. Thirteen SNPs of CASR, VDR, and CYP genes were selected for pharmacogenetic analysis.Results: CYP3A4 rs4646437 was found to be associated with the PK of cinacalcet under fasting conditions (P<0.01). Subjects carrying T alleles of rs4646437 appeared to metabolize cinacalcet poorly. The C max and AUC of subjects in the non-fasting group were significantly higher (P<0.0001) than those in the fasting group. The T max , CL/F, and Vd/F in the fasting group were significantly higher (P<0.0001) than those in the non-fasting group. In the fasting group, the geometric least square mean ratios (T/R) of the C max and AUC 0-t were 109.89% and 105.33%, and the corresponding 90% CIs were 98.36-122.79% and 98.04-113.15%, respectively. In the non-fasting group, the T/R of the C max and AUC 0-t were 100.74% and 99.09%, and the corresponding 90% CIs were 92.65-109.54% and 94.79-103.58%, respectively. All adverse events (AEs) were mild, and no serious adverse events (SAEs) occurred during the bioequivalence trial.Conclusions: Following our investigation, we reached the following conclusions: CYP3A4 rs4646437 may affect cinacalcet PK; the reference and test preparations of cinacalcet were bioequivalent under fasting and non-fasting conditions and were safe to use; and dietary factors had a significant effect on the PK of cinacalcet, in that exposure to the drug increased when cinacalcet was taken after eating.

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The associations of genetic polymorphisms inCYP1A2andCYP3A4with clinical outcomes of breast cancer patients in northern China

Cited by 14 publications

References 30 publications

Catechol‐o‐methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours

Catechol‐o‐methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours

Association of CYP19A1 and CYP1A2 genetic polymorphisms with type 2 diabetes mellitus risk in the Chinese Han population

Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects

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