Mariano Tamura Vieira Gomes

Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women

Introduction.We evaluated the association between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type 1 (AT 1)-receptor A1166C polymorphisms. Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer. Results.The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, χ2); and for AT1receptor were:AA,AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, χ 2).The results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls. Conclusions.The ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes.The ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible target for developing genetic markers for breast cancer.

Estrogen receptor alpha polymorphism and susceptibility to uterine leiomyoma

Uterine leiomyoma is the most frequent pelvic tumor found in female genital tract. Some studies have suggested an association between single nucleotide polymorphisms (SNPs) in estrogen receptors genes with susceptibility in developing uterine leiomyoma. In this work, we estimated the frequency of two SNPs: one located in the intron 1 (rs9322331) and other in the exon 1 (rs17847075) of the estrogen receptor alpha (ESR1) gene in 125 women with uterine leiomyoma and 125 healthy women. To do this we used a PCR-RFLP method with MspI and HaeIII restriction enzymes to respectively detect C/T SNPs in the intron 1 and in the exon 1 of ESR1. To our knowledge this is the first study aimed to investigate the association of ESR1 SNPs with the risk of developing uterine leiomyoma in Brazilian women. Our results showed that the allele frequencies of the exon 1 and the intron 1 of the ESR1 gene did not differ between cases and controls (P = 0.325 and 0.175, respectively). Furthermore, our findings provided little support for the association of these SNPs on ESR1 with leiomyoma. However, we found that the SNP in the intron 1 of the ESR1 gene was underrepresented in the Brazilian female population.

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The χ2 test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

The catechol-O-methyltransferase (COMT) gene polymorphism and prevalence of uterine fibroids

OBJECTIVE To assess the possible association between the catechol-O-methyltransferase (COMT) polymorphism and uterine fibroids in Brazilian women. DESIGN Case-control study. SETTING Department of Gynecology; teaching hospital. PATIENT(S) One hundred twenty-four premenopausal women with fibroids, and 193 postmenopausal controls not presenting the disease. INTERVENTION(S) The subjects were classified as white or non-white (black and mulatto), and COMT genotypes were determined. DNA was extracted from the uterus of cases and from peripheral blood of controls and submitted to polymerase chain reaction (PCR) and agarose gel electrophoresis. MAIN OUTCOME MEASURE(S) The presence of the COMT polymorphism was recorded for all patients, and the frequency and distribution among cases and controls were compared according to race. Binomial log regression models were used to estimate odds-ratios (OR) for uterine volumes of <290 cm(3) (small fibroids) vs. those >290 cm(3) (large fibroids). Potential confounding variables (age, race and parity) were added to the model. RESULTS Genotypes positive for the COMT polymorphism (heterozygous or mutant homozygous) were found in 45% of white and 28.9% of non-white women (p = .013) and the polymorphic allele frequencies in these groups were 27.2% and 16.3%, respectively (p = .006). However, there were no clear differences between patients and controls within the white subgroup with regard to the presence of COMT polymorphism-containing genotypes (41.5% vs. 46.0%, respectively) (p = .60), or for the polymorphic allele frequency (26.8% vs. 27.3%, respectively) (p = .92). For non-white women, there were also no differences between cases and controls for the frequency of polymorphic genotypes (28.9% vs. 28.9%, respectively) (p = .995), or for the polymorphic allele frequency (17.8 vs. 14.5, respectively) (p = .565). Estimated OR for small or large fibroids in association with the polymorphic allele revealed a positive association between the allele with lower activity and large fibroids (vs. small) (OR = 3.3; 95% confidence interval [CI] = 1.31-8.46). The adjusted OR was 4.35 (95% confidence interval [CI] = 1.58-11.9). CONCLUSIONS The catechol-O-methyltransferase polymorphism is a risk factor for the development of large uterine fibroids in Brazilian women suffering from fibroids.

Association of the CYP17 gene polymorphism with risk for uterine leiomyoma in Brazilian women

Background. Uterine leiomyoma is the most common pelvic tumor in women of reproductive age. It is well established that endogenous sex hormones are involved in disease pathogenesis, and polymorphisms in genes encoding enzymes which act in the metabolism of steroid hormones, such as that for cytochrome P450c17α enzyme (CYP17), may therefore play a role in fibroid genesis. Variations in this gene have been thought to influence the susceptibility to hormone-related diseases. A single nucleotide polymorphism (T→C) [rs1042386] in promoter region of CYP17 may alter its transcription. The present study was conducted to investigate the association between this polymorphism and the presence of uterine leiomyoma in Brazilian women. Methods. Genotyping of CYP17 was performed in 121 uterine fibroid patients and 120 unaffected women, using polymerase chain reaction and restriction fragment-length polymorphism analysis. Results. No significant difference in the CYP17 genotype distribution was noted between cases and controls (p = 0.165). Conclusion. These findings suggest that the CYP17 gene polymorphism studied is unlikely to be associated with risk for uterine leiomyoma in Brazilian women.

The role of MSP I CYP1A1 gene polymorphism in the development of uterine fibroids

The cytochrome P-450 1A1 (CYPA1A) gene plays an important role in the metabolization of estrogen and is therefore a candidate marker for fibroids. In a case-control study, we were unable to demonstrate any association between MSP I CYP1A1 polymorphism and the risk of leiomyoma in Brazilian women.

Role of glutathione S-transferase (GSTM1) gene polymorphism in development of uterine fibroids

Glutathione S-transferase (GSTM1) plays an important role in the excretion of catechol estrogens and is therefore a candidate marker for fibroids. However, this case-control study demonstrated no association between GSTM1 polymorphism and the risk of leiomyoma in Brazilian women.

Polimorfismo do receptor de progesterona como fator de risco para o parto prematuro

PURPOSE to investigate the association between gene polymorphism of the progesterone receptor (PROGINS) and the risk of premature birth. METHODS In this case-control study, 57 women with previous premature delivery (Case Group) and 57 patients with delivery at term in the current pregnancy and no history of preterm delivery (Control Group) were selected. A 10 mL amount of peripheral blood was collected by venipuncture and genomic DNA was extracted followed by the polymerase chain reaction (PCR) under specific conditions for this polymorphism and 2% agarose gel electrophoresis. The bands were visualized with an ultraviolet light transilluminator. Genotype and allele PROGINS frequencies were compared between the two groups by the χ2 test, with the level of significance set at value p < 0.05. The Odds Ratio (OR) was also used, with 95% confidence intervals. RESULTS PROGINS genotypic frequencies were 75.4% T1/T1, 22.8% T1/T2 and 1.8% T2/T2 in the Group with Preterm Delivery and 80.7% T1/T1, 19.3% T1/T2 and 0% T2/T2 in the term Delivery Group. There were no differences between groups when genotype and allele frequencies were analyzed: p = 0.4 (OR = 0.7) and p = 0.4 (OR = 0.7). CONCLUSIONS the present study suggests that the presence of PROGINS polymorphism in our population does not constitute a risk factor for premature birth.

Impacto da embolização arterial do leiomioma uterino no volume uterino, diâmetro do mioma dominante e na função ovariana

PURPOSE: To evaluate the impact of uterine artery embolization (UAE) on uterine volume (UV), greater myoma diameter (GMD) and ovarian function three months after the procedure, by transvaginal pelvic ultrasonography (TVPUS) and by the determination of follicle-stimulating hormone (FSH). METHODS: Thirty patients with leiomyomas were submitted to UAE. TVPUS and FSH determination were performed before and three months after UAE. UV was determined in cm³, GMD in cm and FSH in IU/mL. Data are reported as as mean standard deviation (SD) and were analyzed statistically by the nonparametric Mann-Whitney test. RESULTS: Twenty-nine patients were analyzed. Before UAE, mean UV was 402.4 165.9 cm³ and GMD was 5.9 2.1 cm. After UAE, mean UV was 258.9 118.6 cm³ and GMD was 4.6 1.8 cm. Mean FSH concentration was 4.9 3.5 IU/mL before UAE and 5.5 4.7 IU/mL after UAE, with p=0.5. There was a 35% reduction of UV and a 22% reduction of GMD, with no changes in FSH values after three months. CONCLUSION: The procedure significantly reduced UV and GMD but did not cause a significant increase in FSH levels, thus causing no changes in ovarian function.

Avaliação da proporção de colágeno no tecido uterino antes e após tratamento do leiomioma uterino pela embolização arterial

PURPOSE: to analyze histomorphometric consequences of the uterine arteries embolization (UAE) in the uterine tissue, especially by collagen tissue quantification through uterine biopsy, before and after treatment of uterine leiomyoma. METHODS: 15 patients with symptomatic leyomioma and/or infertility, submitted to UAE, participated in the study according to the study exclusion criteria, after having signed an informed consent. Uterine biopsy was performed in the secretory phase of the menstrual cycle, before and three months after the procedure, to evaluate the collagen. After the histological processing of the material, 3 µ slices were prepared, some of them dyed with hematoxiline-eosin (HE) and others with the specific dye for collagen fibers (Picrosirius red). Then, the slides were examined and interpreted, and the collagen quantified. The amount was calculated as the percent of the area composed by collagen, and the result expressed in mean±standard deviation (SD). Data has then been submitted to statistical analysis by Students paired t test (p<0.05). RESULTS: the presence of smooth muscle cells was observed in the biopsies performed before the treatment, surrounded by a rich network of collagen fibers, which are part of the tumor, blood vessels and fibroblast nuclei. On the slides of biopsies performed after the treatment, it was observed the presence of widespread coagulation necrosis, vascular thrombosis, calcification and lymphoplasmocitary infiltration areas and clear reduction of the collagen component. The percentage of collagen fibers was higher in the pre-UAE group (84.07±1.41), than in the post-UAE (81.05±1.50) group, with p<0.0001, and 95% confidence interval (CI95%) from 2.080 to 3.827. CONCLUSION: the quantitative and qualitative collagen reduction clearly shows that the proposed treatment is efficient in reducing the tumoral mass, composed mainly by collagen fibers intermingled with neoplasic smooth muscle cells. Nevertheless, complementary studies are needed to investigate the functional and biological consequences of these histological changes.