Ismael Dale Cotrim Guerreiro da Silva

Universidade Federal de São Paulo, Guarulhos, Estado de Sao Paulo, Brazil

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Publications (22)56.43 Total impact

  • Article: Evaluation of demographic, clinical characteristics, and genetic polymorphism as risk factors for pelvic organ prolapse in Brazilian women.
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    ABSTRACT: Verify the association between genital prolapse, other risk factors and a polymorphism in exon 31 of the collagen III-a1 gene (COL3A1). The etiology of genital prolapse is multifactorial, and genetic defects have been proposed. Also, there is evidence that changes in collagen may be responsible for defects in pelvic floor support. The exon 31 polymorphism results in structural changes in the triple helical of the collagen and appears to lead to abnormal synthesis of type III collagen. Basic science study. The studied group consisted of 107 patients with stage III and IV genital prolapse (POP-Q). The control group included 209 women with stage 0 and I prolapse. After extracting genomic DNA from the peripheral blood, the exon 31 COL3A1 polymorphism was typed by restriction fragment length polymorphism analysis. Association between genital prolapse and exon 31 COL3A1 polymorphism. No statistically significant differences in genotype and allele frequencies were found between cases and controls (P = 0.75 and 0.66, respectively). Multiple logistic regression analyses identified age (OR = 1.05; 95%CI = 1.01-1.10), BMI (OR = 1.09; 95%CI = 1.01-1.17), presence of at least one vaginal delivery (OR = 7.22; 95%CI = 1.84-28.27), positive family history of POP (OR = 2.27; 95%CI = 1.05-4.93) and a macrosomic foetus (OR = 2.91; 95%CI = 1.24-6.79) as independent risk factors for genital prolapse. In contrast, the number of caesarean deliveries was found to be an independent protective factor (OR = 0.43; 95%CI = 0.24-0.78). The type III collagen exon 31 polymorphism is not a risk factor for pelvic genital prolapse in this sample.
    Neurourology and Urodynamics 05/2011; 30(7):1325-8. · 2.96 Impact Factor
  • Article: Evaluation of demographic, clinical characteristics, and genetic polymorphism as risk factors for pelvic organ prolapse in brazilian women
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    ABSTRACT: Objective Verify the association between genital prolapse, other risk factors and a polymorphism in exon 31 of the collagen III-a1 gene (COL3A1).SettingThe etiology of genital prolapse is multifactorial, and genetic defects have been proposed. Also, there is evidence that changes in collagen may be responsible for defects in pelvic floor support. The exon 31 polymorphism results in structural changes in the triple helical of the collagen and appears to lead to abnormal synthesis of type III collagen.DesignBasic science study.PopulationThe studied group consisted of 107 patients with stage III and IV genital prolapse (POP-Q). The control group included 209 women with stage 0 and I prolapse.Methods After extracting genomic DNA from the peripheral blood, the exon 31 COL3A1 polymorphism was typed by restriction fragment length polymorphism analysis.Main outcome measuresAssociation between genital prolapse and exon 31 COL3A1 polymorphism.ResultsNo statistically significant differences in genotype and allele frequencies were found between cases and controls (P = 0.75 and 0.66, respectively). Multiple logistic regression analyses identified age (OR = 1.05; 95%CI = 1.01–1.10), BMI (OR = 1.09; 95%CI = 1.01–1.17), presence of at least one vaginal delivery (OR = 7.22; 95%CI = 1.84–28.27), positive family history of POP (OR = 2.27; 95%CI = 1.05–4.93) and a macrosomic foetus (OR = 2.91; 95%CI = 1.24–6.79) as independent risk factors for genital prolapse. In contrast, the number of caesarean deliveries was found to be an independent protective factor (OR = 0.43; 95%CI = 0.24–0.78).Conclusions The type III collagen exon 31 polymorphism is not a risk factor for pelvic genital prolapse in this sample. Neurourol. Urodynam. 30:1325–1328, 2011. © 2011 Wiley-Liss, Inc.
    Neurourology and Urodynamics 05/2011; 30(7):1325 - 1328. · 2.96 Impact Factor
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    Article: Involvement of GDF-9, leptin, and IGF1 receptors associated with adipose tissue transplantation on fertility restoration in obese anovulatory mice.
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    ABSTRACT: The aim was to analyze the effect of adipose tissue transplantation on growth differentiation factor-9 (GDF-9), insulin growth factor 1 receptor (IGF1R), and leptin receptor (LEPR) protein expression in ovaries of obese anovulatory mice. Leptin-deficient female (ob/ob) and wild-type mice were divided into untreated ob/ob mice and gonadal white adipose tissue transplanted ob/ob mice, with evaluation after 7, 15, and 45 days and compared to control wild-type mice. The corporal weight and glycemia levels increased in the obese group concomitant with polymicrocyst formation and abundant estrone, mimicking anovulatory disease. In the treated group after 45 days, glycemia, weight, ovarian size, and number of follicles were decreased and corpora lutea were decreased. The analysis of GDF-9 revealed that, whereas control ovaries presented follicular localization, the obese ovary lacked this protein. On the other hand, obese ovaries showed elevated expression of IGF1R that was normalized after the transplantation. Finally, LEPR was reduced in obese ovaries, and adipose tissue transplantation was efficient in returning it to normal levels. In conclusion, the adipose tissue transplantation, especially after 45 days, seems to stimulate ovulation, supported by the fact that several proteins involved in ovulation returned to basal levels.
    Gynecological Endocrinology 05/2011; 27(10):759-66. · 1.58 Impact Factor
  • Article: The role of MSP I CYP1A1 gene polymorphism in the development of uterine fibroids.
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    ABSTRACT: 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.
    Fertility and sterility 12/2010; 94(7):2783-5. · 3.97 Impact Factor
  • Article: [Endometrial polyps: clinical and epidemiological aspects and analysis of polymorphisms].
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    ABSTRACT: To evaluate the clinical and epidemiological risk factors for endometrial cancer in postmenopausal women with endometrial polyps, as well as the genetic polymorphism of the progesterone receptor (PROGINS). A case-control study was designed with 160 postmenopausal women with endometrial polyps, compared to a normal Control Group of 400 postmenopausal women. The genotyping of PROGINS polymorphism was determined by the polymerase chain reaction. Clinical and epidemiological data were compared between benign endometrial polyps and 118 of the control subjects. Variables were also compared with regard to benign and malignant endometrial polyps. Comparison of the epidemiological variables between groups showed a significant difference for age, ethnicity, time since menopause, parity, tamoxifen use, hypertension and breast cancer, all of them more prevalent in the polyp group. After adjustment for age, statistical significance remained only for parity (OR=1.1), hypertension (OR=2.2) and breast cancer (OR=14.4). There were six cases of malignant polyps (3.7%). The frequency of bleeding was 23.4% for benign polyps and 100% for malignant polyps, with large polyps being detected in 54.6% of the benign cases and in 100 of the malignnat ones. The frequency of arterial hypertension was 54.5% for benign polyps and 83.3% for the malignant ones. The frequency of PROGINS T1/T1, T1/T2 and T2/T2 polymorphism was 79.9%, 19.5% and 0.6%, respectively, for the polyp group, and 78.8%, 20.8% and 0.5% for the Control Group. Elderly age, hypertension, and breast cancer were significantly associated with endometrial polyps. The presence of PROGINS polymorphism was not significantly associated with endometrial polyps. The incidence of malignant polyps was low and strongly associated with bleeding, large-sized polyp and arterial hypertension.
    Revista brasileira de ginecologia e obstetrićia: revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia 07/2010; 32(7):327-33.
  • Article: Structural analysis of three peptides related to the transmambranic helix VI of AT1 receptor.
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    ABSTRACT: Angiotensin II (AII) is the main active product of the renin angiotensin system. Better known effects of AII are via AT1 receptor (AT1R). Expression of AT1R mutants (L265D and L262D) in CHO cells increased cAMP formation when compared to CHO cells expressing the wild type (WT) AT1R. Morphological transformation of CHO cells transfected with mutants correlated with their increased cAMP formation. DNA synthesis was inhibited in these cells too, indicating that cAMP promotes inhibitory effects on transfected CHO cells growth and causes their morphological change from a tumorigenic phenotype to a non-tumorigenic one. To assess the importance of leucine 262 and 265 in determining AT1R structure by means of a comparative structural analysis of two mutant peptides and of a wild-type fragment. Three peptides had their conformation compared by circular dichroism (CD): L262D(259-272), L265D(259-272) (mutants) and WT(260-277). Secondary structures were: beta-turn for WT and L262D and random coil for L265D. Strong correlation was found in the results of biochemical, cellular and structural approaches used to compare WT AT1R to mutant types. Random coil structure of the L265D mutant may be a key point to explain those changes observed in biochemical (binding and signal transduction) and proliferation assays (Correa et al., 2005). beta-Turn formation is an important step during early protein folding and this secondary simple structure is present in L262D and WT, but not in L265D. Therefore, leucine 265 seems to play a crucial role in determining an entirely functional AT1R.
    Neuropeptides 12/2009; 44(2):115-8. · 1.55 Impact Factor
  • Article: Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS.
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    ABSTRACT: Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.
    American Journal Of Pathology 08/2009; 175(1):215-24. · 4.89 Impact Factor
  • Article: P53 Arg72Pro polymorphism in gastric cancer patients.
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    ABSTRACT: Polymorphism in codon 72, exon 4 of p53 may alter apoptosis and cancer progression. P53 Arg72Pro genotype was assessed by PCR from 84 gastric cancer patients and 185 controls. The control group was comparable in sex, race, age, smoking, and alcohol intake to the cancer group. There was no difference among the frequency of the alleles or genotypes between the groups. P53 Pro/Pro was associated to a lower risk of metastatic disease (p = 0.02) but not to lymph nodes metastasis or worst prognosis. Arg/Arg or Arg/Pro genotype may be associated to metastatic disease.
    Journal of Gastrointestinal Cancer 07/2009; 40(1-2):41-5.
  • Article: Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women.
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    ABSTRACT: 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. 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. The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, chi(2)); and for AT(1)receptor were:AA,AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, chi( 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. 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.
    Journal of Renin-Angiotensin-Aldosterone System 04/2009; 10(1):51-8. · 2.44 Impact Factor
  • Article: Role of glutathione S-transferase (GSTM1) gene polymorphism in development of uterine fibroids.
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    ABSTRACT: 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.
    Fertility and sterility 10/2008; 91(4 Suppl):1496-8. · 3.97 Impact Factor
  • Article: The catechol-O-methyltransferase (COMT) gene polymorphism and prevalence of uterine fibroids.
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    ABSTRACT: To assess the possible association between the catechol-O-methyltransferase (COMT) polymorphism and uterine fibroids in Brazilian women. Case-control study. Department of Gynecology; teaching hospital. One hundred twenty-four premenopausal women with fibroids, and 193 postmenopausal controls not presenting the disease. 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. 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. 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). The catechol-O-methyltransferase polymorphism is a risk factor for the development of large uterine fibroids in Brazilian women suffering from fibroids.
    Maturitas 09/2008; 60(3-4):235-8. · 2.77 Impact Factor
  • Article: Association of the CYP17 gene polymorphism with risk for uterine leiomyoma in Brazilian women.
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    ABSTRACT: 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 P450c17alpha 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. Genotyping of CYP17 was performed in 121 uterine fibroid patients and 120 unaffected women, using polymerase chain reaction and restriction fragment-length polymorphism analysis. No significant difference in the CYP17 genotype distribution was noted between cases and controls (p = 0.165). These findings suggest that the CYP17 gene polymorphism studied is unlikely to be associated with risk for uterine leiomyoma in Brazilian women.
    Gynecological Endocrinology 07/2008; 24(7):373-7. · 1.58 Impact Factor
  • Article: Prevalence of human papillomavirus in squamous cell carcinoma of the tongue.
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    ABSTRACT: Oncogenic human papillomaviruses (HPVs) are important agents in the genesis of gynecological cancer, and have also been implied in the genesis of oral cancer. With the purpose of evaluating the relationship between HPV and squamous cell carcinoma (SCC) of the tongue, a case-control study was performed. Fifty white male patients who were smokers and had the histological diagnosis of SCC of the tongue were selected. The control group was composed of 10 matched patients with no clinical evidence of tongue lesions. Polymerase chain reaction (PCR) was used to detect the presence of HPV genome in fresh-frozen tissue specimens from SCC of the tongue margin. Thirty-seven patients (74%) had a positive PCR for oncogenic papillomavirus, and only 1 specimen (10%) of the control group was positive for nononcogenic papillomavirus. Based on the statistical analysis of this study there was a 25.6% higher risk for SCC of the tongue to harbor oncogenic HPV than the healthy control tongue tissue.
    Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 11/2007; 104(4):497-500. · 1.50 Impact Factor
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    Article: Gene analysis in patients with premature ovarian failure or gonadal dysgenesis: a preliminary study.
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    ABSTRACT: The aim of this study was to evaluate the presence of mutations in the coding region of the QM gene and fragile X in patients with premature ovarian failure and gonadal dysgenesis. After approval by the local Ethics Committee, blood samples, in EDTA, of 100 normally ovulating women, 23 with premature ovarian failure (POF) and 14 with gonadal dysgenesis 46XX, aged less than 40 years, were screened for mutation in the QM gene coding region. All patients with POF have 46, XX karyotype and serum levels of follicle-stimulating hormone (FSH) over 30 mIU/mL. In addition, all samples from patients with premature ovarian failure underwent analysis for fragile X. The QM gene located at a hotspot region (Xq28) showed five points of mutations in a patient with premature ovarian failure. Four of them were able to change the amino acid sequence of the protein. None of our patients were diagnosed as having pre or mutant X fragile syndrome. Our study suggests that Xq28 (QM gene) may be involved in ovary failure. However, further studies are needed to confirm this hypothesis.
    Maturitas 09/2007; 57(4):399-404. · 2.77 Impact Factor
  • Article: The progesterone receptor gene polymorphism, PROGINS, may be a factor related to the development of uterine fibroids.
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    ABSTRACT: To assess the possible association between the polymorphic allele of the progesterone receptor gene, named PROGINS, and uterine leiomyomas. Case-control study. Department of Gynecology. Teaching hospital. One hundred twenty-two premenopausal women with fibroids and 125 postmenopausal controls not presenting the disease. The subjects were classified as White or non-White (Black and Mulatto) and the progesterone receptor genotyping was performed, with DNA extracted from uterus in cases and from peripheric blood in controls and submitted to polymerase chain reaction (PCR) and agarose gel electrophoresis. The presence of the PROGINS allele was recorded, and its frequency as well as the genotypic distribution among cases and controls were compared according to race. PROGINS-positive genotypes (heterozygous or mutant homozygous) were found in 19% of White and 11% of non-White women, and allelic frequency of PROGINS in the groups was 10.4% and 6.2%, respectively. Comparing patients and controls, we observed a significant difference among non-White women, both regarding presence of PROGINS-positive genotypes (4.9% vs. 25%, respectively), and PROGINS allele frequency (3.3% vs. 12.5%, respectively). There was no significant difference in PROGINS-positive genotypes among White cases and controls (16.4% vs. 20.6%, respectively), and in their allelic frequency (8.2% vs. 11.9%, respectively). The odds ratio showed reduced risk of fibroids related to PROGINS-positive genotypes in non-White women (odds ratio = 0.16, 95% confidence interval: 0.04-0.66), but not among White subjects (odds ratio = 0.76, 95% confidence interval: 0.33-1.74). The PROGINS polymorphism revealed to be protective in terms of uterine fibroids in Brazilian non-White women.
    Fertility and sterility 06/2007; 87(5):1116-21. · 3.97 Impact Factor
  • Article: The effects of soy extract on the uterus of castrated adult rats.
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    ABSTRACT: The aim of this study was to evaluate the effects of different doses of a standardized soy extract on the uterus of castrated rats. Fifty-six adult castrated female Wistar rats were randomly divided into seven groups (eight animals in each) that received: GI--drug vehicle (propylene glycol); GII--soy extract 10mg/kg per day; GIII--soy extract 50mg/kg per day; GIV--soy extract 100mg/kg per day; GV--soy extract 300mg/kg per day; GVI--soy extract 600mg/kg per day; GVII-conjugated equine estrogens (CEE) 200microg/kg per day. After 21 days of treatment, all animals were sacrificed and fragments of the uterine horns were immediately removed, fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The endometrial cell proliferation index was determined with the PCNA antibody PC-10 and expressed as the percentuals of the PCNA-positive nuclei relative to the total countings. Other fragments were immediately frozen in liquid nitrogen for RNA extraction and VEGF analysis using RT-PCR technique. The minimal dose of soy extract that produced a significant increase of the morphometric parameters was 100mg/kg (GIV). The maximum effects on endometrial and myometrial morphometry were detected in the groups treated with 300 and 600mg/kg of soy extract (groups V and VI) and CEE (GVII). The expression of PCNA in the endometrial epithelium and stroma was increased by treatment with 100-600mg/kg per day of soy extract (groups IV-VI) or with CCE (group VII). Doses equal to or higher than 50mg/kg of soy extract (groups III-VI) and CEE stimulated the expression of VEGF. The treatment of adult castrated rats during 21 days with doses of 100mg/kg per day or higher of soy extract may determine significant proliferation in the endometrium and myometrium.
    Maturitas 03/2007; 56(2):173-83. · 2.77 Impact Factor
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    Article: Genetic polymorphism of GSTM1 in women with breast cancer and interact with reproductive history and several clinical pathologies.
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    ABSTRACT: Due to the conflicting results regarding the association between breast cancer and the GSTM1 null mutation, our aim was to research this association in a Brazilian population and correlations with smoking, reproductive history and several clinical pathologies. A case-control study was performed on 105 women with breast cancer and 278 controls. Extraction of DNA was accomplished according to the protocol of the GFX kit and polymorphism analysis by the PCR technique. The control and experimental groups were compared and statistical analysis assessed by X2 or Fisher's exact test. The deletion in the GSTM1 gene in the breast cancer group had a prevalence of 32 (30.4%) individuals with the presence of null mutation. In the control group, the null mutation was present in 104 (37.4%) women. Upon comparison of the two groups, no statistically significant difference of the GSTM1 gene was observed, with an odds ratio (OR) of 0.74, 95%, confidence interval (CI) 0.45 - 1.20, p = 0.277. The results conclusively show that single gene GSTM1 polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, in this study no correlation was found between GSTs and smoking, reproductive history and several clinical pathologies with respect to cancer risk.
    Biological research 02/2005; 38(2-3):273-81. · 1.03 Impact Factor
  • Article: A comparative study of MMP-2 in vulvar neoplasms.
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    ABSTRACT: To investigate differences in MMP-2 protein expression in VIN, vulvar invasive carcinoma, and lichen sclerosus, we performed an immunohistochemical study in which tissue samples from individuals affected by these conditions were compared with normal vulvar tissue. A total of 57 cases were selected, as follows: 14 cases of vulvar invasive carcinoma, 22 of vulvar intraepithelial neoplasia (6 of VIN I, 5 of VIN II, and 11 of VIN III), 9 of vulvar lichen sclerosus, and 12 samples of normal vulvar tissue. Immunohistochemistry was done with primary monoclonal antibodies against MMP-2 and quantification of the immunostaining was done by counting the number of antigen-positive stromal cells per 1000 stromal cells. Normal vulvar tissue had a median score of 37.99 stromal cells positive for MMP-2. The median scores for VIN I/II and lichen sclerosus were 41.98 and 46.51, respectively, with no statistical differences when compared to the normal group. Invasive cancer had a score statistically higher (160.36) than any of the other groups. Invasive vulvar carcinoma had a score statistically higher of MMP-2 than normal tissue, VIN, and lichen sclerosus.
    Gynecologic Oncology 06/2004; 93(2):454-7. · 3.89 Impact Factor
  • Article: The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.
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    ABSTRACT: Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximately 23,500 genes, of which only approximately 1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.
    Proceedings of the National Academy of Sciences 11/2003; 100(23):13418-23. · 9.68 Impact Factor
  • Article: [Role of the genetic polymorphism of p53 (codon 72) gene in colorectal cancer].
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    ABSTRACT: Polymorphisms are genetic variations that can occur in sequences of codons, leading to defective proteins. p53 is the most commonly gene affected in human cancer. The polymorphism of this gene occurs by a substitution of a base in codon 72 and may increase the risk of cancer. To investigate the possible association between p53 arginine/72 proline polymorphism and susceptibility to colorectal cancer. This polymorphism was studied by polymerization chain reaction using specific primers in 100 patients with colorectal cancer paired by sex and age to 100 patients without cancer. Alcohol and tobacco used by all the patients and clinical aspects as stage, grade of differentiation and recurrence in the case group was compared with the genotype analyzed. The frequency of homozygosis for arginine was 56% in the cancer group and 58% in the control group. No significant difference was observed among both groups. This genotype was more frequent in colorectal cancer patients stage IV than in stage I (80% versus 14%). There was no significant difference between genotypes and alcohol, tobacco, grade of differentiation or recurrence. Homozygosity for arginine was the most prevalent genotype in both groups. The frequency of codon 72 proline/arginine p53 gene polymorphism was not correlated with a higher risk of colorectal cancer. Arginine/arginine genotype was more prevalent in advanced cancer patients (stage IV).
    Arquivos de Gastroenterologia 43(1):8-13.