Analysis of risk factors associated with recurrence of canine babesiosis caused by Babesia gibsoni.

Canine babesiosis due to Babesia gibsoni (B. gibsoni) displays severe clinical manifestations. Recurrence of babesiosis after anti-babesial treatment is observable in over 10 % of the patients. The present study ascertains the risk factors and cumulative incidence of recurrence of canine babesiosis. For a sample of 145 dogs diagnosed with acute babesiosis, the following parameters were assessed over a period of 16 weeks: haematological parameters, status of anaemia, platelet count, total WBC count, haemoglobin concentration and RBC count, concurrent haemoparasitism, and secondary immune mediated haemolytic anaemia (IMHA). Patient demographics such as age, breed, sex were also recorded. The potential risk factors were statistically evaluated by the cumulative incidence function and the Kaplan-Meier method. The recurrent infections were observed in 11.8 % of the study sample. The following factors were found to associate with increased risk of recurrence: Rottweiler breed (CIR 21.8 % ± 6.9 %; p < 0.05), secondary IMHA (CIR 28.7 % ± 11.3 %; p < 0.05), RBC counts < 2 × 106/µl on the day of diagnosis (CIR 16 % ± 4.6 %; p < 0.05), and persistent anaemia over 20 days post treatment (CIR 29.14 ± 7.9 %; p < 0.001). Dogs with concurrent haemoparasitic infections were predicted to have a fatal outcome in the survival analysis (disease related mortalities 25 % ± 13 %; p < 0.001). According to the findings, veterinarians need to pay attention to Rottweiler breed, dogs with secondary IMHA, concurrent haemoparasitism, low RBC counts on diagnosis and those with persistent anaemia to reduce the risk of relapse.

Identification of differentially expressed genes in pathways of cerebral neurotransmission of anovulatory mice.

Polycystic ovary syndrome is the classic example of loss of functional cyclicity and anomalous feedback. In this case, the excessive extra-glandular production and conversion of androgens to estrogens are the pathophysiological basis of the chronic anovulation. The literature describes an experimental model of the polymicrocystic ovary in obese diabetic mice with insulin resistance. The fact that these animals exhibit obesity, insulin resistance, and infertility demonstrates their skill as an experimental model for polycystic ovary. A recent study using long protocol for up to 40 weeks showed that anovulatory and obese mice transplanted with adipose tissue from animals with normal weight have multiple changes in their phenotype. These changes include reduction of body weight, prevention of obesity, insulin level normalization, and insulin tolerance tests, preventing the elevation of steroids and especially the reversal of fertility restoration with anovulation. Considering that there are close relationships between the ovulation process and the central nervous system, we propose to evaluate the gene expression levels of 84 different genes involved in neurotransmission and insulin pathways in addition to examining the neurolipidosis differential murine brain before and after reversal of anovulation. The present study showed changes in gene expression of molecular markers in brain tissue of animals for brain neurotransmission pathways as well as pathways for insulin. GABAergic genes, muscarinic, serotonin receptors, receptor tyrosine kinase, and genes of interleukin 6 showed overexpression profile. There was also a change in the lipid content in anovulatory brain, obesity, and insulin resistant mice (Ob-/Ob-) compared with controls. The re-introduction of leptin in these animals appears to reverse, at least in part, this profile.

The influence of biopsy in cervical high-grade squamous intraepithelial lesion, evaluated by HPV E6/E7 mRNA, Pap test, and conization results.

OBJECTIVE: To evaluate the influence of biopsy on cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: A study was conducted involving 124 women underwent colposcopy-guided biopsy. At the first appointment, the women answered the survey questionnaire, cervical samples were collected for Papanicolaou (Pap) testing and the HPV E6/E7 mRNA test. At the second appointment at three to four months after the first, samples were collected from 81 patients with indications for conization, Pap test, and HPV E6/E7 mRNA testing before they underwent the procedure. PCR was used to detect HPV mRNA. The percentage of negative results before and after the biopsy was evaluated. The agreement between the tests results was evaluated using Cohen's kappa. RESULTS: Sixty-two patients (76.4%) were between 21 and 40 years of age, 35 (43.2%) had four or more pregnancies, 41 (50.5%) had their sexual debut at 16 years of age or more, and 52 patients (64.2%) had undergone five or more Pap tests. The initial biopsy was negative for CIN2/3 in 14 (12.3%) patients; however, all patients were submitted to conization. Among those women with biopsy showing CIN2/3 (66 [81.5%]), 7.41% showed CIN1 and 14.81% were negative in the conization (kappa = 0.2052). The E6/E7 test performed before and after biopsy showed the best level of agreement by the kappa coefficient (0.7491) Conclusions: A higher percentage of negative results were observed in the histopathology, cytopathology, and E6/E7 after biopsy, suggesting that biopsy could affect the regression of CIN.

Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer.

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.

Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density.

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.

p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis.

We hypothesized that p27(kip1) overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27(kip1) was obtained by transduction of p27(kip1) in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27(kip1) expression in endometrial cells primary culture. The effect of p27(kip1) overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without endometriosis were also evaluated. The VEGF levels were evaluated 1 and 7 days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27(kip1) overexpression in the endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the endometriosis group (p < 0.001) and an increase in apoptotic cells was observed. In the endometriosis group, significant downregulation of VEGF expression was observed 7 days after p27(kip1) overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control protein (p27(kip1)) and angiogenesis (VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic cell therapy.

Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

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.

TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population.

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.

Persistence or clearance of human papillomavirus infections in women in Ouro Preto, Brazil.

Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer. We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18-75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the follow-up. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer.

Interleukin-6 -174 G/C promoter gene polymorphism in nasal polyposis and asthma.

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.

The relationship between estrogen receptor gene polymorphism and mammographic density in postmenopausal women.

OBJECTIVE: To assess the relationship between the presence of PVUII and XBAI polymorphisms in the estrogen receptor α gene and mammographic density in postmenopausal women. METHODS: For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADS(®) 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized). Blood samples were available to extract DNA according to KIT GFX(®) protocol. PCR-RFLP was then used to identify the polymorphisms. RESULTS: There was a high degree of agreement among the three readers to determine the mammographic density (κ > 0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI polymorphism was found in 135 (71.4%) women. Parity (p = 0.02) and body mass index (p < 0.0001) were associated with mammographic density. It was observed that, for the XBAI polymorphism, women with two mutated alleles were approximately 2.5 times more likely to be classified in the dense breasts group (p = 0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p = 0.02). CONCLUSIONS: There was no significant association of the PVUII polymorphism in the estrogen receptor α gene with mammographic density (p = 0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and there was an increased frequency of wild-type homozygous and heterozygous women with fat-replaced breasts (p = 0.01).

Human papillomavirus infection in Brazilian women with normal cervical cytology.

We examined the prevalence of human papillomavirus (HPV) infection in a sample of Brazilian women presenting normal cervical cytology. Possible interactions between patient characteristics and HPV infection were analyzed in order to provide background data to improve cervical cancer screening and prophylaxis. Cervical samples of 399 women, received for routine evaluation in the Health Department of Ouro Preto, MG, Brazil, were subjected to HPV-DNA testing by PCR with MY09/11 primers. HPV-positive specimens were typed by RFLP. A structured epidemiological questionnaire was administered to each woman. HPV prevalence among these cytologically normal women was 11%. Twelve viral types were detected, the most common being HPV-16, -6, -61, -83, and -66. HPV was more prevalent in younger women; high-risk viral types were detected in 61% of the infected women and 27% of the infected women had multiple HPV infections. Significant associations of HPV infection were found with age, literacy, residence, marital status, lifetime number of sexual partners, and parity. We detected a great diversity of HPV types in women with normal cytology. This kind of information about local populations is useful for HPV prevention and vaccination strategies.

Influence of the CYP17 polymorphism on vasomotor symptoms in postmenopausal women: a pilot study.

OBJECTIVE: To evaluate the influence of CYP17 polymorphism on menopausal symptoms after estrogen treatment. METHODS: A total of 130 women were recruited, but only 100 of these were selected according to inclusion and exclusion criteria; they were treated with 0.3 mg/day conjugated equine estrogens. One year later, the study was completed by 71 women. The analysis of the Kupperman menopausal index symptoms was made with information provided by the patients on daily diary cards. Blood samples were analyzed and the women were divided into two groups based on the CYP17, 5'-untranslated region: group A (wild-type homozygote and heterozygote) and group B (mutated homozygote). RESULTS: The values for the Kupperman menopausal index were similar in both groups at baseline. The symptoms in both groups decreased after 1 year of treatment when compared to those at baseline. The improvement rate was approximately 27.09% and 32.18%, in groups A and B, respectively. The levels of estrogen after treatment were higher in both groups in comparison with the baseline values. The testosterone level rose in group B with the 1-year treatment (0.48 + 0.16 ng/ml), reaching a higher level than the level in group A after treatment. The sex hormone binding globulin (SHBG) level showed a significant increase after the 1-year treatment in group B, surpassing both the baseline and the after-treatment values in group A (p < 0.01). CONCLUSION: Our data suggest that the CYP17 polymorphism did not influence the action of estrogen on menopause symptoms during the 1-year treatment. The extra production of estrogen and androgen may have been countered by the elevation of SHBG levels.

Cytokine and hormonal profile in serum samples of patients undergoing controlled ovarian stimulation: interleukin-1beta predicts ongoing pregnancy.

BACKGROUND: Changes in the endometrium are not regulated exclusively by ovarian hormones; the immune system has also been implicated in normal endometrial function, similar to processes taking place during inflammatory and reparative path. Many cytokines are crucially important for reproductive processes, and the role of cytokines in the female reproductive system function has been broadly investigated during controlled ovarian stimulation (COS) for IVF attempts. The aim of this study was to evaluate the levels of serum cytokines and hormones, and the clinical outcomes of women who underwent COS and ICSI procedures. METHODS: The study prospectively included 96 patients (aged 22-43 years, unexplained or male infertility, n = 61; female infertility factors, n = 35) who underwent ICSI cycles. Serum levels of interleukin (IL-8, IL-6, IL-1beta, IL-10, IL-12), tumour necrosis factor and leukaemia-inhibitory factor (LIF) and the hormones FSH, estradiol, progesterone, anti-Mullerian hormone and Inhibin-B were measured on the day of oocyte retrieval. RESULTS: The ongoing pregnancy rate was 25.3%. The presence of serum IL-1beta positively affected the implantation rate (P = 0.004) and increased the chance of becoming pregnant by 15 fold. Furthermore, the percentage of patients with detectable serum IL-1beta levels who conceived (62.5%) was higher than those who failed to conceive (37.5%; P = 0.019). The LIF was undetectable in all serum samples, and no other factors influenced the clinical outcomes of patients undergoing ICSI cycles. CONCLUSIONS: Our findings revealed that detectable serum levels of IL-1beta on the day of oocyte retrieval in patients undergoing COS and ICSI are predictive of successful implantation and ongoing pregnancy.

Effect of estrogen receptor-alpha (ESR1) gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy

Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT). A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1) gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G) frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029). Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032). No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

Effect of estrogen receptor-alpha (ESR1) gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy.

Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT). A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1) gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G) frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029). Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032). No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

Fas/CD95 promoter polymorphism gene and its relationship with cervical carcinoma.

OBJECTIVE: Apoptosis is an important fail-safe control in human papillomavirus (HPV)-associated carcinogenesis. We tested the hypothesis that the A/G polymorphism at -670 of Fas promoter is associated with an increased risk for cervical cancer, using a matched case-control setting. METHODS: The material in this case-control study consisted of 91 patients with cervical carcinoma and 176 population-based control subjects, recruited between 2002 and 2004; all the ethnic Brazilian women had histologically confirmed cervical carcinoma. Control subjects were age-matched; healthy women who were selected following a negative cervical cytology and normal colposcopy. Fas genotyping was performed using a PCR-RFLP technique. RESULTS: No significant difference existed in the distribution of the Fas polymorphisms (wild, heterozygous, mutant) between the cases and controls. The heterozygous (OR: 4.85, 95% CI: 1.1-22.6) genotypes among the younger (< 48 yrs) cancer patients were almost 5-fold increased, as compared with the wild type. No such increase was observed among the patients older than 48 years. CONCLUSIONS: Our data suggest that 670A/G polymorphism in the promoter region of the death receptor Fas is associated with an increased risk of cervical cancer among Brazilian women under 48 years. The mechanisms would be the inhibition of apoptosis by Fas -670G allele-mediated down-regulation of Fas transcription.

Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.

Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density.

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.

Prognostic markers of low-grade squamous intraepithelial lesions: the role of topoisomerase IIalpha and active caspase-3.

PURPOSE: To study the relationship between topoisomerase IIalpha, active caspase-3 expressions and HPV DNA in uterine cervices with low-grade squamous intraepithelial lesions (LSIL). METHODS: Forty women with LSIL and 32 without cervical neoplasia diagnosed through cytologic and histopathologic examination were evaluated regarding topoisomerase IIalpha and active caspase-3 expressions and HPV DNA detection using PCR (GP5/GP6) in cervicovaginal smears. RESULTS: The mean percentage of cells immunomarked by topoisomerase in the group with LSIL was 11.62% while in the control it was 4.13% (p < 0.0001). In the presence of HPV DNA, topoisomerase expression was higher in the group with productive viral infection than in nonneoplastic tissue (p = 0.004). Caspase-3 expression was observed in 17 patients with LSIL (42.5%) and in five without cervical neoplasia (15.63%). CONCLUSION: The use of topoisomerase IIalpha and active caspase-3 in cervical biopsies may help to define the prognosis of HPV cervical infection.