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1.
Int J Ophthalmol ; 17(3): 491-498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721519

RESUMO

AIM: To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction (SMILE) with different myopic diopters. METHODS: Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study. Patients were allocated into three groups based on the preoperative spherical equivalent (SE): low myopia (SE≥-3.00 D), moderate myopia (-3.00 D>SE>-6.00 D) and high myopia (SE≤-6.00 D). Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times (1wk, 1, 3, 6mo, and 1y). Posterior mean elevation (PME) at 25 predetermined points of 3 concentric circles (2-, 4-, and 6-mm diameter) above the best fit sphere was analyzed. RESULTS: All surgeries were completed uneventfully and no ectasia was found through the observation. The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively (1mo: P=0.017; 3mo: P=0.018). The effect of time on ΔPME was statistically significant (2-mm ring: P=0.001; 4-mm ring: P<0.001; 6-mm ring: P<0.001). The effect of different corneal locations on ΔPME was significant except 1wk postoperatively (1mo: P=0.000; 3mo: P=0.000; 6mo: P=0.001; 1y: P=0.001). Posterior corneal stability was linearly correlated with SE, central corneal thickness, ablation depth, residual bed thickness, percent ablation depth and percent stromal bed thickness. CONCLUSION: The posterior corneal surface changes dynamically after SMILE. No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery. SMILE has good stability, accuracy, safety and predictability.

2.
Front Cell Dev Biol ; 9: 628128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842457

RESUMO

BACKGROUND: Dermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD. METHODS: A total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated in vitro. RESULTS: Serum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all p < 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9-44.7) vs. 16.2 (10.0-26.9) ng/mL, p < 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts. CONCLUSIONS: Among anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

3.
J Int Med Res ; 48(9): 300060520957447, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32961068

RESUMO

OBJECTIVE: To investigate the efficacy and safety of ab interno trabeculotomy using the VISCO360® Viscosurgical System (Sight Sciences, Inc., Menlo Park, CA, USA) combined with cataract extraction in the treatment of primary open-angle glaucoma (POAG). METHODS: Patients with POAG who underwent ab interno trabeculotomy combined with cataract extraction were retrospectively analyzed. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), the number of antiglaucomatous medications, and complications were recorded preoperatively and 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years postoperatively. RESULTS: Thirty-four patients (40 eyes) with POAG were included in this study, including 20 men (22 eyes) and 14 women (18 eyes). Compared with the preoperative IOP, the postoperative IOP was significantly lower at each time point. The greatest reduction in IOP was 60.7% at 1 month after surgery. The BCVA was also significantly improved at each postoperative time point. The number of antiglaucomatous medications used by the patients was significantly lower postoperatively than preoperatively. CONCLUSION: Ab interno trabeculotomy combined with cataract extraction is effective and safe for treatment of POAG.


Assuntos
Extração de Catarata , Catarata , Glaucoma de Ângulo Aberto , Trabeculectomia , Catarata/complicações , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Masculino , Estudos Retrospectivos , Resultado do Tratamento
4.
Infect Drug Resist ; 13: 69-79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021321

RESUMO

BACKGROUND: Unfortunately, the eradication rate of Helicobacter pylori (H. pylori) treatment is markedly decreasing in recent years and the major reason is antibiotic resistance. Our study was designed to determine the effect and safety of H. pylori eradication treatment based on the molecular pathologic antibiotic resistance. METHODS: 261 patients were analyzed retrospectively, including 111 patients who were treated for the first time (one group as First-treated) and 150 patients who failed at least once in bismuth quadruple therapy (another group as Re-treatment). Antibiotic resistance was examined by Real-time PCR detection and conventional PCR and sequencing method. The eradication rate (ER) was compared per intention to treat (ITT) and per protocol (PP) between the two groups. RESULTS: The resistance rates to amoxicillin, clarithromycin, fluoroquinolone and tetracycline were 5.5%, 42.1%, 41.7% and 12.9% in the 111 first-treated patients, and 11.7%, 79.7%, 70.7% and 30.0% in the 150 re-treatment patients. The ERs in the ITT and PP analyses were 92.79% (95% CI, 87.98-97.60%, n=111) and 98.10% (95% CI, 95.48-100%, n=105), respectively, in the first-treated patients and 90.67% (95% CI, 86.01-95.32%, n=150) and 95.10% (95% CI, 91.57-98.64%, n=143), respectively, in the re-treatment patients. No significant differences were shown in the ERs between two group patients, and no serious adverse events were found. CONCLUSION: H. pylori eradication treatment based on molecular pathologic antibiotic resistance showed good effect and safety in both first and re-treated patients.

5.
Int J Ophthalmol ; 12(9): 1415-1419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544036

RESUMO

AIM: To observe the changes of microcellular structure of meibomian glands (MGs) in type 2 diabetes mellitus (DM), and to explore its correlation with the duration of diabetes. METHODS: The study assessed 132 eyes of 132 patients with type 2 diabetes mellitus (DM group) and 100 eyes of 100 non-diabetic participants (NDM group). All patients underwent the examination of the Keratograph 5M system to obtain the meibography which were used to evaluate the structure dropout of the MGs. And then laser scanning confocal microscopy (LSCM) was performed for observing the acinar cells and ducts of the MGs to obtain the following parameters: the MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD) and MG acinar shortest diameter (MGASD). The examination results of the right eye were selected for analysis. RESULTS: Compared with that in NDM group, the meiboscore was significantly higher (Z=-4.057, P<0.001), and there were more MGs dropout in DM group. With the prolongation of the course of diabetes, the absence of MGs aggravated and the MGs dropout score increased (r=0.596; P<0.001). LSCM showed that there were various cytological alterations in acinar cells of MGs with the progress of diabetes duration, such as expansion, atrophy or fibrosis of MG acinar units, decreased density of MG acinar units, deposition of lipid substances, infiltration of inflammatory cells, proliferation of fibrous tissues, etc. And the opening of the glandular duct changed from smooth at the beginning to narrow, blocked, fibrotic and so on. Compared with that in NDM group, the MGAUD in DM group was significantly lower (Z=-9.713; P<0.001), the MGALD and MGASD were significantly larger (Z=-9.751, -6.416; P<0.001). With the duration of diabetes, the MGAUD reduced, the MGASD increased (r=0.860, 0.364, P<0.001); but the MGALD had no correlation with diabetic duration (r=0.133, P=0.151). CONCLUSION: With the progress of diabetes, the meibomian glandular acinar cells of diabetic patients show various manifestations. Those changes may result in the dysfuction of the MGs, tear film instability and dry eye symptoms in patients with type 2 DM.

6.
Int J Ophthalmol ; 9(12): 1740-1744, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28003972

RESUMO

AIM: To investigate the morphological changes of meibomian glands in patients with type 2 diabetes mellitus (DM). METHODS: Of 118 eyes (118 patients) with type 2 DM (DM group) and 100 eyes of 100 control subjects (control group) were enrolled. After completing an ocular surface disease index (OSDI) questionnaire, the non-invasive tear film break-up time (NI-BUT) and the structure of the meibomian glands (MGs, meibography) were assessed by the Keratograph 5M system. Partial or complete loss of MG was scored for each eyelid from grade 0 (no loss) to grade 3 (lost area was >2/3 of the total MG area), which were also examined by laser scanning confocal microscopy (LSCM). The primary outcomes were meibomian gland acinar unit density (MGAUD), meibomian gland acinar longest diameter (MGALD) and meibomian gland acinar shortest diameter (MGASD). RESULTS: Compared with control group, the OSDI was significantly higher in DM group (Z=-5.916; P<0.001), while the NI-BUT was significantly lower (Z=-7.765; P<0.001). Keratograph showed that there were more MGs dropout in DM group than that in control group. The meiboscore was significantly higher in DM group compared with control group (Z=-3.937; P<0.001). LSCM revealed that there were cytological alterations of MGs in DM group compared with control group, which included enlargement of MG acinar units and decreased in density of MG acinar units. Specifically, there were lower MGAUD, larger MGALD and MGASD in DM group than control group (Z=-10.120, -9.4442, -7.771; P<0.001). CONCLUSION: Compared with the normal control participants, the patients with type 2 DM had more unstable tear films and severe symptoms of dry eye. Using Keratograph 5M system and LSCM, we found that the patients with type 2 DM had more significant morphological and cytological changes and dysfunction in MGs.

7.
Int J Ophthalmol ; 9(2): 286-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26949653

RESUMO

AIM: To investigate the changes of retinal function in non-pathological myopic subjects using multifocal electroretinography (mfERG) and to correlate the data with the central macular thickness obtained using optical coherence tomography (OCT). METHODS: One hundred and thirteen subjects (113 eyes) with age range from 18 to 35y were enrolled in the study. The subjects were divided into four groups according to spherical equivalent (SE) and axial length (AL): emmetropia group (EG, n=31; SE: +0.75 to -0.50 D; AL: 22 to 24 mm), low and medium myopia group (LMMG, n=26; SE: >-0.50 to -6.00 D; AL: >24 to 26 mm), high myopia group (HMG, n=34; SE: >-6.00 to -10.00 D; AL: >26 to 28 mm) and super high myopia group (SHMG, n=22; SE: >-10.00 D; AL:>28 mm). The P1 amplitude density, P1 amplitude, and P1 implicit time of the first-order kernel mfERG responses were obtained and grouped into five rings. The central subfield macular thickness (CST) was obtained using macular cube 512×218 scan of Cirrus HD-OCT. RESULTS: With the increasing of eccentricity, the first positive peak (P1) amplitude density (P=0.0000, 0.0001, 0.0021 in ring 1-3 respectively) and P1 amplitude (all P=0.0000 in ring 1-5) of each group decreased. With the increasing of myopia, P1 implicit time gradually extended (all P=0.0000 in ring 1-3). The average CST in four diagnostic groups was 241.56±12.72 µm, 244.56±12.19 µm, 254.33±11.61 µm, 261.75±11.83 µm respectively. With the increasing of myopia, CST increased (P<0.001). There was negative relationship between CST and P1 amplitude, P1 amplitude density (r=-0.402, P<0.001; r=-0.261, P=0.003). There was positive relationship between CST and P1 implicit time (r=0.34, P<0.001). CONCLUSION: With the increasing of myopia, P1 amplitude density and P1 amplitude of the first-order reaction gradually reduced. This showed potential decline in retinal function in myopia. To some extent it may reflect the functional disorder or depression of the visual cells. The exact mechanism needs further study.

8.
Ying Yong Sheng Tai Xue Bao ; 26(4): 1231-6, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26259468

RESUMO

Abstract: Fusarium wilt is a soil borne disease caused by plant continuous cropping in monoculture Chrysanthemum morifolium 'Youxiang' monoculture not only declines plant quality and yield but also decreases soil enzymes and soil microbial diversity over successive cultivation. In this article, the effects of fungicide (Carbendazim MBC), antifungal enhanced bio-organic fertilizer (BOF), and their combined application on the quality and soil enzymes activities of Chrysanthemum morifolium 'Youxiang' in continuous cropping systems were investigated. The results showed that both bioorganic fertilizer (BOF) and fungicide (MBC) single application could effectively prevent the occurrence of Fusarium wilt disease of cut chrysanthemum. Bio-organic fertilizer application was more effective on root activity, soil enzymes activities and quality (shoot height, stem diameter, leaf SPAD value, ray floret number, shoot fresh mass) improvement of cut chrysanthemum, while fungicide single application was responsible for soil enzymatic activities suppression to some extent. The combined application treatment (MBC+BOF) showed the best effects on quality improvement and soil enzyme activities promotion.


Assuntos
Agricultura/métodos , Chrysanthemum/crescimento & desenvolvimento , Fertilizantes , Fungicidas Industriais , Microbiologia do Solo , Solo/química , Chrysanthemum/microbiologia , Enzimas/química , Fusarium , Folhas de Planta , Raízes de Plantas , Caules de Planta
9.
Eur J Obstet Gynecol Reprod Biol ; 184: 65-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25463638

RESUMO

OBJECTIVE: Centrosome aberrations and cell-cycle deregulations have important implications for the development of endometrial carcinoma. AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation. This study aimed to investigate whether genetic polymorphisms in these four genes may contribute to endometrial carcinoma susceptibility and progression in Chinese Han women. STUDY DESIGN: A total of twenty-two single nucleotide polymorphisms (SNPs) were selected according to the public HapMap database (HapMap Data Release #27; Chinese Beijing population), and genotyped using TaqMan Realtime PCR method in 530 endometrial adenocarcinoma cases and 825 age-matched controls from Chinese Han women. Then, haplotype blocks were reconstructed according to our genotyping data. RESULTS: For AURKA, the rs911162 was associated with increased risk of endometrial carcinoma [in co-dominant model: adjusted odds ratio (aOR) = 4.92, 95% CI = 1.24-19.55, P = 0.0235]. The haplotype GA (rs6064391 + rs911162) in block 1 of AURKA was also associated with increased risk of endometrial carcinoma (aOR = 1.25, 95% CI = 1.07-2.06, P = 0.0189). For BRCA1, the minor allele homozygotes of rs8067269 could decrease the risk of endometrial carcinoma (in co-dominant models: aOR = 0.52, 95% CI = 0.34-0.80, P = 0.0032), so was the haplotype CTCAG (rs8176323 + rs8176199 + rs3737559 + rs8067269 + rs2070833) (aOR = 0.69, 95% CI = 0.50-0.95, P = 0.0234). Moreover, we found several associations between genetic variations in CCNE1, BRCA1 and AURKA and clinicopathological parameters. CONCLUSIONS: This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may contribute to endometrial carcinoma susceptibility or progression in Chinese Han women.


Assuntos
Adenocarcinoma/genética , Aurora Quinase A/genética , Proteína BRCA1/genética , Ciclina E/genética , Quinase 2 Dependente de Ciclina/genética , Neoplasias do Endométrio/genética , Predisposição Genética para Doença , Proteínas Oncogênicas/genética , Adenocarcinoma/patologia , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Progressão da Doença , Neoplasias do Endométrio/patologia , Feminino , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
10.
Int J Ophthalmol ; 7(1): 122-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24634877

RESUMO

AIM: To investigate the changes of retinal thickness in macula of high myopic eyes using spectral domain optical coherence tomography (OCT). METHODS: Middle-aged and young myopic patients were divided into three groups according to their refractive error/axial length: low and medium myopia group (LMMG), high myopia group (HMG) and super high myopia group (SHMG). Cirrus HD-OCT was used to evaluate total average macular thickness, central subfield thickness, inner/outer macular thickness and macular volume. The differences among experimental groups were analyzed by one-factor analysis of variance. Associations between macular thickness and refractive error/axial length were analyzed by Pearson correlation analysis. RESULTS: There was no significant difference in age among the three groups (P=0.2789). The mean refraction error in the LMMG, HMG, and SHMG groups was -2.49±1.38D, -8.53±1.95D and -13.88±1.76D, respectively (P<0.001). The central subfield thickness of three groups was 244.56±12.19µm, 254.33±11.61µm and 261.75±11.83µm, respectively, and there were statistically significance between random two groups. The total average macular thickness, inner/outer macular thickness, and macular volume decreased with increased myopia/axial length. Average foveal thickness had negative correlations with refractive error (P<0.001), and positive correlations with axial length. The inferior and temporal inner macular thickness, all the quadrants of outer ring, total average macular thickness and macular volume featured positive correlations with refractive error, and negative correlations with axial length. Average foveal thickness, superior and temporal inner macular thicknesses, and temporal outer macular thickness was lower in females compared to males. CONCLUSION: With an increase in myopia degree/axial length, the average foveal thickness increased and the inner/outer macular thickness decreased. Females featured thicker average foveal thickness, and thinner macular thickness compared to males.

11.
Oncol Rep ; 30(4): 1848-52, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23912275

RESUMO

Transforming growth factor (TGF)-ß-inducible nuclear protein 1 (TINP1) is a novel gene, which is localized at chromosome 5q13 where frequent abnormalities in hairy cell leukemia (HCL) occur. The present study investigated the effects of TINP1 knockdown or overexpression on the viability and gene expression of various tumor cell lines. siTINP1 was designed to knock down TINP1 expression. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were performed to assess gene expression; the cell counting kit-8 (CCK-8) assay was used to detect cell viability, and luciferase and flow cytometry assays were used to determine gene activity. TINP1 was widely expressed in various cell lines. In addition, TINP1 siRNA was able to knock down TINP1 expression in HeLa cells. TINP1 overexpression significantly promoted tumor cell proliferation, which may be associated with the downregulation of p53 expression. Furthermore, TINP1 promoted a number of cell lines to the S phase of the cell cycle. TINP1 promotes cell proliferation and significantly reduces p53 and p21 expression.


Assuntos
Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Células Jurkat , Neoplasias/genética , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno , Proteínas de Ligação a RNA , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/biossíntese
12.
PLoS One ; 7(11): e49296, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23185313

RESUMO

BACKGROUND: Somatic alterations of cyclin-dependent kinase 2 (CDK2)-cyclin E complex have been shown to contribute to breast cancer (BC) development and progression. This study aimed to explore the effects of single nucleotide polymorphisms (SNPs) in CDK2 and CCNE1 (a gene encoding G1/S specific cyclin E1 protein, formerly called cyclin E) on BC risk, progression and survival in a Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: We herein genotyped 6 haplotype-tagging SNPs (htSNPs) of CCNE1 and 2 htSNPs of CDK2 in 1207 BC cases and 1207 age-matched controls among Chinese Han women, and then reconstructed haplotype blocks according to our genotyping data and linkage disequilibrium status of these htSNPs. For CCNE1, the minor allele homozygotes of three htSNPs were associated with BC risk (rs3218035: adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI] = 1.69-6.67; rs3218038: aOR = 1.81, 95% CI = 1.22-2.70; rs3218042: aOR = 2.64, 95% CI = 1.31-5.34), and these three loci showed a dose-dependent manner in increasing BC risk (P(trend) = 0.0001). Moreover, the 5-SNP haplotype CCGTC, which carried none of minor alleles of the 3 at-risk SNPs, was associated with a favorable event-free survival (hazard ratio [HR] = 0.53, 95% CI = 0.32-0.90). Stratified analysis suggested that the minor-allele homozygote carriers of rs3218038 had a worse event-free survival among patients with aggressive tumours (in tumour size>2 cm group: HR = 2.06, 95% CI = 1.06-3.99; in positive lymph node metastasis group: HR = 2.41, 95% CI = 1.15-5.03; in stage II-IV group: HR = 2.03, 95% CI = 1.09-3.79). For CDK2, no significant association was found. CONCLUSIONS/SIGNIFICANCE: This study indicates that genetic variants in CCNE1 may contribute to BC risk and survival in Chinese Han population. They may become molecular markers for individual evaluation of BC susceptibility and prognosis. Nevertheless, further validation studies are needed.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Ciclina E/genética , Quinase 2 Dependente de Ciclina/genética , Predisposição Genética para Doença , Células Germinativas/metabolismo , Proteínas Oncogênicas/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , China , Progressão da Doença , Etnicidade/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Haplótipos/genética , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco
13.
Breast Cancer Res Treat ; 136(1): 241-51, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23001753

RESUMO

Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09-0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18-2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97-14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.


Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular/genética , Estudos de Associação Genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Alelos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , China , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Quinases Relacionadas a NIMA , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
J Pathol ; 225(4): 535-43, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21598251

RESUMO

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Ubiquitina-Proteína Ligases/genética , Povo Asiático , Aurora Quinase A , Aurora Quinases , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/etnologia , Carcinoma Ductal de Mama/patologia , Estudos de Casos e Controles , China/etnologia , Feminino , Humanos
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