RESUMO
The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.
Assuntos
Neoplasias da Mama/genética , Códon/genética , Polimorfismo Genético/genética , Proteína Supressora de Tumor p53/genética , Adulto , Alelos , Brasil , Estudos Transversais , Feminino , Predisposição Genética para Doença/genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Pessoa de Meia-IdadeRESUMO
In this study, we evaluated genetic factors related to the mineral density during post-menopause. We evaluated 110 women in the first 5 years post-menopause, without previous hormone replacement therapy. Cytochrome P450 17 (CYP17) (rs743572), catechol-O-methyl transferase (COMT) (rs4680), and estrogen receptor 1 (ESR1) (rs9322331) were examined for the presence of polymorphisms. Clinical data were collected by anamnesis; all patients had the osseous densitometry examined using a lunar instrument to determine mineral osseous densitometry in the lumbar column (L2-L4). CYP17, COMT, and ESR1 genotyping was carried out by polymerase chain reaction with DNA collected from buccal swabs. The average age was 51.96 years. The average weights of the patients in control and osteopenia groups were 70.25 ± 12.00 and 62.45 ± 11.64, respectively (P = 0.001) and body mass index (P = 0.006; control: 29.43 ± 5.25; osteopenia: 26.72 ± 4.57). Related to CYP17 polymorphisms, 28.18% of women were TT (wild-type homozygous), 60% were TC (heterozygous), and 11.82% were CC (mutated homozygous). Related to COMT polymorphisms, 53.64% of women were GG (wild-type homozygous), 37.27% were GA (heterozygous), and 9.09% were AA (mutated homozygous). Related to ESR1, 53.64% of women were CC (wild-type homozygous), 40.91% were CT (heterozygous), and 5.45% were TT (mutated homozygous). The ESR1 variant allele was significantly higher in the osteopenia group when compared with women in the normal group (P = 0.02). ESR1 may be associated with low mineral osseous densitometry, while CYP17 and COMT gene polymorphisms were not associated with mineral osseous densitometry.
Assuntos
Densidade Óssea/genética , Catecol O-Metiltransferase/genética , Receptor alfa de Estrogênio/genética , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Alelos , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P < 0.05). However, no significant differences were found in the COMT gene polymorphism genotype distributions between the patient and control groups (P > 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.
Assuntos
Catecol O-Metiltransferase/genética , Citocromo P-450 CYP1A1/genética , Neoplasias do Colo do Útero/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , HumanosRESUMO
We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53 11 Glu/Gln or Lys (GAG->CAG or AAG), TP53 72 Arg/Pro (CCG->CCC), and TP53 248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53 11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53 72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wild-type (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53 248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis.
Assuntos
Códon/genética , Endometriose/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Alelos , Brasil , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Interleukin-6 (IL-6) is an inflammatory mediator linked to nasal polyposis and asthma, with a single nucleotide poly- morphism -174 G/C that seems to promote an inflammatory status. We aimed to analyze the relationship between this poly-morhism and asthmatic nasal polyposis patients. METHODOLOGY: Cross-sectional study to investigate IL-6 - 174 G/C genotypes of 45 nasal polyposis with asthma patients, 63 nasal polyposis-only patients, 45 asthma-only patients and 81 subjects without both diseases. Aspirin intolerance and atopy were main exclusion criteria. IL-6 genotyping was performed using the PCR method with specific primers followed by restriction enzyme analysis, classifying patients in GG, GC or CC genotype. RESULTS: The GG genotype was the most frequent in all inflammatory groups. Less than 40% of controls presented with the GG ge- notype. There were significant differences between inflammatory groups and control group. No significant differences were seen when comparing inflammatory groups to each other, other than between nasal polyposis-only group and asthma-only group. CONCLUSION: The IL-6 74 GG genotype was found more frequently in all inflammatory groups than in controls. This genotype could influence nasal polyposis and asthma, and seems to be more important in the latter.