Guarana (Paullinia cupana) Improves Anorexia in Patients with Advanced Cancer.

PURPOSE: Anorexia is prevalent in cancer patients with advanced disease. In this pilot phase II, open label, nonrandomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. METHODS: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in two phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a three-point improvement in the appetite scale in at least three of the first 18 evaluable patients. RESULTS: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only one patient abandoned the protocol due to toxicity (grade II arthralgia). No grade 3 or 4 toxicities and no significant differences in nausea, weight loss, or quality of life (FACT-G) occurred. Only two of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas six patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in the lack of appetite (p = 0.02) and in somnolence (p = 0.0142). CONCLUSION: We concluded that the weight stabilization and increased appetite that we observed in this study justify further studies of guarana in this patient population.

Paullinia cupana para o controle de fogachos em pacientes com câncer de mama: um estudo piloto / Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study

OBJETIVO: Avaliar se a Paullinia cupana diminui o número e a gravidade dos fogachos em mulheres após diagnóstico de câncer de mama. MÉTODOS: Estudo piloto prospectivo fase II realizado com mulheres que sobreviveram ao câncer de mama, que completaram o tratamento pelo menos 3 meses antes e que apresentavam ao menos 14 episódios de fogachos por semana. Utilizando o desenho de Simon para que a primeira etapa fosse considerada positiva, ao menos 9 de 15 mulheres deveriam ter a gravidade dos fogachos diminuída em pelo menos 50%. As pacientes receberam 50mg do extrato seco de Guaraná oralmente 2 vezes por dia por 6 semanas. Foram avaliadas, a gravidade e a frequência dos fogachos. RESULTADOS: Dezoito pacientes iniciaram o tratamento com Paullinia cupana e 15 completaram o estudo. Três pacientes deixaram o estudo imediatamente após iniciarem o tratamento em razão de dificuldade na participação e não adesão. Das 15 pacientes que completaram o estudo, 10 obtiveram diminuição de mais de 50% dos índices de gravidade de fogachos. Durante as 6 semanas de tratamento, diminuições estatisticamente significativas foram observadas tanto no número de fogachos (p=0,0009), quanto nos índices de gravidade (p<0,0001). Paullinia cupana foi bem tolerada, e não houve relato de toxicidade como causa de saída do estudo. CONCLUSÕES: Paullinia cupana pareceu promissora para o controle de fogachos. Estudos mais extensivos são necessários.

OBJECTIVE: To evaluated whether Paullinia cupana decrease number and severity of hot flashes in breast cancer survivors. METHODS: This was a prospective phase II pilot study. We studied female breast cancer survivors who had completed the cancer treatment 3 months previously and who were experiencing at least 14 hot flashes per week. At least 9 of the 15 patients were required to have a decrease of at least 50% in hot flash severity score in keeping with the Simon Design. Patients received 50mg of dry extract of Paullinia cupana orally twice a day for 6 weeks. We assessed both frequency and severity of hot flashes. RESULTS: A total of 18 patients started the Paullinia cupana treatment, and 15 completed the study. Three patients left the study immediately after starting the treatment because of personal difficulties in participation or noncompliance. Of the 15 patients who completed the study 10 had a decrease of more than 50% in hot flash severity scores. During the 6 weeks of treatment, statistically significant decreases were seen in both numbers of hot flashes (p=0.0009) and severity scores (p<0.0001). Paullinia cupana was well tolerated, and there were no instances of discontinuation because of toxicity. CONCLUSIONS: Paullinia cupana appears promising for controlling hot flashes. More extensive studies seem warranted.

Purified dry extract of Paullinia cupana (guaraná) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: an early discontinuation study.

PURPOSE: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. METHODS: We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory (BFI) questionnaire scores after 1 week of systemic chemotherapy. PC-18 was administered at 37.5 mg by mouth two times per day (PO bid), starting after 1 week of chemotherapy, for 3 weeks (induction phase). Patients who had an improvement in or stabilization of their BFI scores were randomized to receive either PC-18 at the same dose or placebo for the following 3 weeks (maintenance phase). RESULTS: After PC-18 treatment, the BFI fatigue scores improved or stabilized in 36 out of the 40 patients (mean BFI score difference = 2.503; 95% confidence interval: 1.716-3.375, p = .0002). Three weeks after randomization (16 patients on PC-18 and 17 on placebo), we observed no significant differences in the BFI, Functional Assessment of Chronic Illness Therapy, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores between patients randomized to PC-18 versus placebo. CONCLUSIONS: We conclude that the PC-18 extract may be effective for the treatment of CRF in patients with a variety of solid tumors. A conditioning effect, which was observed in patients who had a beneficial effect of PC-18 on CRF, may explain the better than expected fatigue scores of the placebo-treated patients.

Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study.

OBJECTIVE: To evaluated whether Paullinia cupana decrease number and severity of hot flashes in breast cancer survivors. METHODS: This was a prospective phase II pilot study. We studied female breast cancer survivors who had completed the cancer treatment 3 months previously and who were experiencing at least 14 hot flashes per week. At least 9 of the 15 patients were required to have a decrease of at least 50% in hot flash severity score in keeping with the Simon Design. Patients received 50mg of dry extract of Paullinia cupana orally twice a day for 6 weeks. We assessed both frequency and severity of hot flashes. RESULTS: A total of 18 patients started the Paullinia cupana treatment, and 15 completed the study. Three patients left the study immediately after starting the treatment because of personal difficulties in participation or noncompliance. Of the 15 patients who completed the study 10 had a decrease of more than 50% in hot flash severity scores. During the 6 weeks of treatment, statistically significant decreases were seen in both numbers of hot flashes (p=0.0009) and severity scores (p<0.0001). Paullinia cupana was well tolerated, and there were no instances of discontinuation because of toxicity. CONCLUSIONS: Paullinia cupana appears promising for controlling hot flashes. More extensive studies seem warranted.

The nuclear factor-kB functional promoter polymorphism is associated with endometriosis and infertility.

INTRODUCTION: An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Nuclear factor-kB (NF-kB) plays a key role in the immune and inflammatory response and modulates cell proliferation, apoptosis, adhesion, invasion, and angiogenesis in many cell types involved in the development of endometriosis. We hypothesized a possible relationship between the NFKB1 promoter regulatory polymorphism and endometriosis and/or infertility. METHODS: A genetic association study comprising 172 infertile women with endometriosis, 77 women with idiopathic infertility and 189 controls was performed. Detection of the -94 insertion/deletion ATTG (rs28362491) polymorphism in the NFKB1 gene was done using the RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) technique. The results were statistically analyzed, and a p-value <0.05 was considered significant. RESULTS: Single-marker analysis revealed a significant association between the -94 insertion/deletion ATTG polymorphism and endometriosis-related infertility (p=0.014, OR=1.47, 95% CI=1.09-1.97), especially in moderate/severe disease cases. Considering the idiopathic infertility group, a significant association was also found (p=<0.001, OR=2.01, 95% CI=1.35-2.98), suggesting that the -94 insertion/deletion ATTG polymorphism is associated with endometriosis and/or infertility. CONCLUSION: In the population sample studied, the -94 insertion/deletion ATTG polymorphism in the NFKB1 gene was positively associated both with moderate/severe endometriosis and idiopathic infertility.

The prevalence and influence of self-reported conflicts of interest by editorial authors of phase III cancer trials.

PURPOSE: To assess the frequency with which editorial authors report personal conflict of interest and investigate a possible association between the presence of such conflicts and favorable opinion. METHODS: Eligible studies were editorials of phase III clinical trials of antitumor drugs or symptom management published from January 2007 to December 2009 in four top oncology journals. Data from the editorials were collected and each editorial opinion was classified as favorable, neutral or unfavorable with respect to the experimental therapy. RESULTS: Fifty-four editorials were included: 23 (43%) reported at least one conflict of interest, with the most frequent one being consultancy fees. Conclusions of editorial authors were classified as favorable in 18 editorials (33%). Sensitivity analysis found an association between self-reported conflict of interest of the editorial author and editorial favorable opinion (RR:2.7; 95% CI 1.2-6.1; p=0.019). DISCUSSION: Besides the high proportion of conflict of interest among editorial authors discussing phase III clinical trials, study interpretation may be influenced by their financial relationships with industry.

Genetic association study of polymorphisms FOXP3 and FCRL3 in women with endometriosis.

OBJECTIVE: To consider a possible cumulative effect of two genetic polymorphisms (FOXP3 C-2383T/rs3761549 and FCRL3 C-169T/rs7528684) that were previously shown to be associated with endometriosis. DESIGN: Genetic association study. SETTING: Human reproduction outpatient clinic of Faculdade de Medicina do ABC. PATIENT(S): One hundred eighty-eight infertile women with endometriosis and 169 controls. INTERVENTION(S): Detection of polymorphisms FOXP3 (C-2383T/rs3761549) and FCRL3 (C-169T/rs7528684) by TaqMan real-time polymerase chain reaction. The results were analyzed statistically. MAIN OUTCOME MEASURE(S): Genotype distribution, allele frequency, and combination analysis of the FOXP3 and FCRL3 polymorphisms. RESULT(S): Single-marker analysis revealed a significant association of FOXP3 C-2383T and FCRL3 C-169T, independently, with endometriosis-related infertility, regardless of the stage of the disease. Considering the combined genotypes of FCRL3 and FOXP3 polymorphisms, a positive association was found between genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT and the risk of endometriosis development. Moreover, a progression of the disease risk was observed according to the presence of one or two copies of risk allele FCRL3 C and only one copy of risk allele FOXP3 T (odds ratio [OR] = 2.14, OR = 3.25, and OR = 6.0, respectively, for genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT). CONCLUSION(S): Our findings support a possible gene-gene interaction leading to a cumulative effect on endometriosis development.

Prevalência do câncer em dois serviços públicos atendidos pela Disciplina de Oncologia e Hematologia da Faculdade de Medicina da Fundação ABC (FMABC) / Cancer prevalence in two public services coordinated by the Department of Oncology and Hematology, ABC Foundation School of Medicine (FMABC)

Objetivos: Analisar as características dos pacientes que frequentam os serviços de Oncologia da FMABC e comparar com as estatísticas acionais e da região. Métodos: Trata-se de um levantamento epidemiológico conduzido de 14/9/2010 a 18/5/2011 nos ambulatórios de oncologia de dois hospitais públicos da região do grande ABC, que tabulou de forma sistemática as características clínicas dos pacientes atendidos. Resultados: Do total de 2.366 pacientes avaliados, 60% eram oriundos do Hospital Mário Covas, 63% eram mulheres, com idade média de 60,25 (12-105) anos. Os tumores mais prevalentes foram: mama (31,6%), colorretal (14,8%), próstata (11,2%), linfoma não Hodgkin (6%) e estômago (3,9%). Do total de pacientes (excetuando-se linfoma não Hodgkin), 15,3% apresentaram metástase no momento da sua inclusão. Conclusões: Em comparação com os dados do INCA para o Brasil e região Sudeste de 2010, nosso serviço apresenta significativamente mais casos de câncer de mama (31,5% FMABC versus 13% Brasil e 13,6% Sudeste) e menor número de casos de câncer de pulmão (2,5% FMABC versus 7,36% Brasil e 6,7% Sudeste). Volumes diferentes de cirurgias oncológicas nos diversos serviços de referência de nossa instituição, assim como maior intensidade de medidas preventivas para câncer de mama podem explicar parte das diferenças observadas. Não podemos excluir, todavia, fatores epidemiológicos específicos regionais para explicar a alta prevalência de câncer de mama na região do ABC.

Gabapentin for the prevention of chemotherapy- induced nausea and vomiting: a pilot study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. METHODS: Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24-120 h after chemotherapy). RESULTS: The proportion of patients achieving complete response improved from 40% to 62.5%, (p = 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%, p = 0.01). Adverse events did not significantly differ between study arms. CONCLUSIONS: Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control.

[Analysis of VDR gene polymorphism Fok1 in infertile women with endometriosis]. / Análise do polimorfismo Fok1 do gene VDR em mulheres inférteis com endometriose.

PURPOSE: to evaluate the frequency of VDR gene polymorphism Fok1 in infertile women with endometriosis and Control and its relation to the disease. METHODS: a case-control study that included 147 infertile women with endometriosis and 154 fertile women without endometriosis as Control. Fok1 polymorphism (rs10735810, T2C), which promotes a T/C exchange in exon 2 of the VDR gene, was identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), that involves the combination of amplification by PCR and digestion with restriction endonuclease. The χ2 test was used to compare allele and genotype frequencies between groups. All p-values were two-tailed and a p-value < 0.05 was considered statistically significant. RESULTS: the TT, TC and CC genotype frequencies of VDR Fok1 polymorphism were 44.2%, 46.9% and 8.9% in infertile women with endometriosis and 41.6%, 50% and 8.4% in the Control Group. No significant difference was found (p=0.8), even when the patients were subdivided according to the stage of endometriosis (p=0.3 for minimal and mild endometriosis and p=0.2 for moderate and severe endometriosis). Alleles T and C were present, respectively, in 67.6% and 32.3% of infertile women with endometriosis (p=0.8), in 63.5% and 36.5% of women with minimal/mild endometriosis (p=0.5), in 72.5% and 27.5% of women with moderate/severe endometriosis (p=0.2), and in 66.6% and 33.4% of the Control Group. No statistically significant difference was found among any groups and the Control. CONCLUSION: the results suggest that VDR gene polymorphism Fok1 does not confer genetic susceptibility to endometriosis-associated infertility in the Brazilian population.

[Analysis of codon 72 polymorphism of the TP53 gene in infertile women with and without endometriosis]. / Análise do polimorfismo no códon 72 do gene TP53 em mulheres inférteis com e sem endometriose.

PURPOSE: to evaluate the frequency of TP53 codon 72 polymorphism in infertile women with endometriosis, women with idiopathic infertility, controls and its relation to the disease. METHODS: a case-control study that included 198 infertile women with endometriosis, 70 women with idiopathic infertility and 169 fertile women without endometriosis as control. Detection of TP53 codon 72 gene polymorphism (rs1042522, Arg/C:Pro/G), that promotes a C/G exchange in the coding region of the gene, was performed by real time Polymerase Chain Reaction (PCR), using the TaqMan system of primers, that flank the implicated region and probes labeled with different fluorescent dyes, one for allele C and other for allele G. When two dyes were observed, the patient was considered to be heterozygous CG. In the presence of only one dye, the individual was considered to be homozygous CC or GG. The χ2 test was used to compare allele and genotype frequencies between groups. All p-values were two-tailed and a p-value <0.05 was considered to be statistically significant. RESULTS: we found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes CC, CG or GG (p=0.7) and alleles C or G (p=0.4) between infertile patients with endometriosis and controls (p=0.4), regardless of the stage of the disease. In relation to infertility, no statistically significant difference in the genotype or allele distribution (p=1.0 and p=0.9, respectively) was observed between idiopathic infertile women and controls. Considering the dominant inheritance model, again, no statistically significant difference was found even in the endometriosis (p=0.5) or the idiopathic infertility group (p=0.9) when compared to controls. Regarding the recessive inheritance model no statistically significant difference was found, with p=0.6 and p=1.0, respectively, for the endometriosis and idiopathic infertility groups. CONCLUSION: the results suggest that the TP53 codon 72 polymorphism does not confer genetic susceptibility to endometriosis and/or infertility in the Brazilian population, not even the severe form of the disease.

Association of FCRL3 -169T/C polymorphism with endometriosis and identification of a protective haplotype against the development of the disease in Brazilian population.

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Fc receptor-like 3 gene (FCRL3) has been proposed as a novel autoimmune predisposing factor. The authors have hypothesized a possible relationship between endometriosis, infertility, and FCRL3 polymorphisms. This was a case-control study that included 170 women with endometriosis-related infertility, 91 women with idiopathic infertility, and 166 controls. Detection of FCRL3 polymorphisms (-169C/T, -110G/A, +358C/G and +1381 A/G) was performed using TaqMan PCR. The results were analyzed statistically and a p value <0.05 was considered significant. Results Single-marker analysis revealed that FCRL3 -169C/T was significantly associated with endometriosis (p = 0.004), regardless of the stage of the disease, p = 0.011 and p = 0.035, respectively to minimal/mild and to moderate/severe endometriosis. No association was found considering -110A/G, +358C/G, and +1381 A/G polymorphisms either for the endometriosis-related infertility group or the idiopathic infertility group. Haplotype analysis of four FCRL3 polymorphisms identified a haplotype GGGC associated with endometriosis (p = 0.026). The haplotype AGAT was associated with protection against endometriosis (p = 0.011) and infertility (p = 0.041). The data from this study point to a possible association of the FCRL3 -169C/T polymorphisms with endometriosis, especially minimal/mild endometriosis, and the haplotype AGAT may be protective against the development of the disease, in Brazilian women. However, these findings clearly need to be replicated in an independent sample and in different populations.

Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis.

OBJECTIVE: To evaluate PAI-1 genotypes in a group of infertile women with or without endometriosis and control subjects. DESIGN: Case-control study. SETTING: Human Reproduction Center of Medicina do ABC Faculty. POPULATION: One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. METHODS: The PAI-1 4G/5G polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. MAIN OUTCOME MEASURES: Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The frequencies of genotypes 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with endometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). CONCLUSION: The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis-associated infertility.

Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis.

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Genetic alterations in the vitamin D receptor gene (VDR) may lead to important defects in gene activation that principally affect immune function. We have hypothesized a possible relationship between endometriosis and/or infertility and the VDR polymorphisms (ApaI, TaqI, FokI, and BmsI). The study was a case-control study including 132 women with endometriosis-related infertility, 62 women with idiopathic infertility, and 133 controls. VDR polymorphisms were studied by restriction fragment length polymorphism. We found relatively similar VDR polymorphism genotype frequencies in cases and controls. When patients with minimal/mild and moderate/severe endometriosis were studied separately, no difference was found. When we compared infertile groups with and without endometriosis there was no statistically significant difference. The data suggest that VDR polymorphisms did not play an important role in the pathogenesis of endometriosis and/or infertility in the Brazilian women studied.

Análise do polimorfismo Fok1 do gene VDR em mulheres inférteis com endometriose / Analysis of VDR gene polymorphism Fok1 in infertile women with endometriosis

OBJETIVO: avaliar a frequência do polimorfismo Fok1 do gene do receptor da vitamina D (VDR) em mulheres inférteis com endometriose e Grupo Controle, e sua associação com a doença. MÉTODOS: estudo caso-controle que incluiu 147 mulheres inférteis com endometriose e 154 mulheres férteis sem endometriose como Controle. O polimorfismo Fok1 (rs10735810, T2C), que promove uma troca de T/C no éxon 2 do gene VDR, foi identificado por PCR-RFLP (análise de polimorfismos de fragmentos de restrição), que envolve a combinação de amplificação por PCR (reação em cadeia da polimerase) e digestão com endonuclease de restrição. O teste do χ2 foi utilizado para comparar as frequências dos genótipos e alelos entre os grupos. Todos os valores de p foram bicaudais, e o nível de significância considerado foi 0,05 (α<0,05). RESULTADOS: os genótipos TT, TC e CC do polimorfismo FokI do gene VDR apresentaram frequência de 44,2 por cento, 46,9 por cento e 8,9 por cento nas mulheres inférteis com endometriose e 41,6 por cento, 50 por cento e 8,4 por cento no Grupo Controle, e não apresentaram diferença significante quando comparados (p=0,8), mesmo quando as pacientes com endometriose foram subdivididas de acordo com o estadiamento da endometriose (p=0,3 para endometriose mínima e leve e p=0,2 para endometriose moderada e grave). Em relação aos alelos, T e C estavam presentes, respectivamente, em 67,6 por cento e 32,3 por cento das mulheres inférteis com endometriose (p=0,8), em 63,5 por cento e 36,5 por cento das mulheres com endometriose mínima/leve (p=0,5), em 72,5 por cento e 27,5 por cento das mulheres com endometriose moderada/grave (p=0,2), e em 66,6 por cento e 33,4 por cento das mulheres do Grupo Controle. Não foi observada diferença estatística significante na comparação entre nenhum dos grupos e o Grupo Controle...

PURPOSE: to evaluate the frequency of VDR gene polymorphism Fok1 in infertile women with endometriosis and Control and its relation to the disease. METHODS: a case-control study that included 147 infertile women with endometriosis and 154 fertile women without endometriosis as Control. Fok1 polymorphism (rs10735810, T2C), which promotes a T/C exchange in exon 2 of the VDR gene, was identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), that involves the combination of amplification by PCR and digestion with restriction endonuclease. The χ2 test was used to compare allele and genotype frequencies between groups. All p-values were two-tailed and a p-value < 0.05 was considered statistically significant. RESULTS: the TT, TC and CC genotype frequencies of VDR Fok1 polymorphism were 44.2 percent, 46.9 percent and 8.9 percent in infertile women with endometriosis and 41.6 percent, 50 percent and 8.4 percent in the Control Group. No significant difference was found (p=0.8), even when the patients were subdivided according to the stage of endometriosis (p=0.3 for minimal and mild endometriosis and p=0.2 for moderate and severe endometriosis). Alleles T and C were present, respectively, in 67.6 percent and 32.3 percent of infertile women with endometriosis (p=0.8), in 63.5 percent and 36.5 percent of women with minimal/mild endometriosis (p=0.5), in 72.5 percent and 27.5 percent of women with moderate/severe endometriosis (p=0.2), and in 66.6 percent and 33.4 percent of the Control Group. No statistically significant difference was found among any groups and the Control...

Análise do polimorfismo no códon 72 do gene TP53 em mulheres inférteis com e sem endometriose / Analysis of codon 72 polymorphism of the TP53 gene in infertile women with and without endometriosis

OBJETIVO: avaliar a frequência do polimorfismo no códon 72 do gene TP53 em mulheres inférteis com endometriose, mulheres com infertilidade idiopática, Grupo Controle e sua associação com a doença. MÉTODOS: estudo caso-controle que incluiu 198 mulheres inférteis com endometriose, 70 mulheres com infertilidade idiopática e 169 mulheres férteis sem endometriose como controles. O polimorfismo no códon 72 do gene TP53 (rs1042522, Arg/C:Pro/G), que promove uma troca de C/G na sequência codante, foi identificado pela reação em cadeia da polimerase (PCR) em tempo real, por meio da utilização de sistema TaqMan de primers, flanqueando a região em questão e sondas marcadas com fluoróforos diferentes, uma para o alelo C, outra para o alelo G. Na observação de dois fluoróforos, o paciente foi considerado heterozigoto para o polimorfismo. Na presença de apenas um fluoróforo, o paciente foi considerado homozigoto CC ou GG. O teste do χ2 foi utilizado para comparar as frequências dos genótipos e alelos entre os grupos. Todos os valores de p foram bicaudais, e o nível de significância considerado foi 0,05 (α <0,05). RESULTADOS: não foi encontrada diferença significativa na frequência dos genótipos CC, CG e GG (p=0,7) e alelos C e G (p=0,4) do polimorfismo no códon 72 do gene TP53 entre pacientes inférteis com endometriose em relação aos controles, independentemente do estágio da doença. Em relação à infertilidade, não houve diferença significativa quanto às mulheres inférteis sem endometriose em relação aos controles na distribuição dos genótipos e alelos (p=1,0 e p=0,8, respectivamente). Considerando o modelo de herança dominante, não houve diferença estatística significante tanto no grupo de endometriose (p=0,5) como no grupo de infertilidade idiopática (p=0,9) em relação aos controles. Observando o modelo recessivo, também não houve diferença significante (p=0,6 e p=1,0, respectivamente) para os grupos de endometriose e infertilidade idiopática ...

PURPOSE: to evaluate the frequency of TP53 codon 72 polymorphism in infertile women with endometriosis, women with idiopathic infertility, controls and its relation to the disease. METHODS: a case-control study that included 198 infertile women with endometriosis, 70 women with idiopathic infertility and 169 fertile women without endometriosis as control. Detection of TP53 codon 72 gene polymorphism (rs1042522, Arg/C:Pro/G), that promotes a C/G exchange in the coding region of the gene, was performed by real time Polymerase Chain Reaction (PCR), using the TaqMan system of primers, that flank the implicated region and probes labeled with different fluorescent dyes, one for allele C and other for allele G. When two dyes were observed, the patient was considered to be heterozygous CG. In the presence of only one dye, the individual was considered to be homozygous CC or GG. The χ2 test was used to compare allele and genotype frequencies between groups. All p-values were two-tailed and a p-value <0.05 was considered to be statistically significant. RESULTS: we found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes CC, CG or GG (p=0.7) and alleles C or G (p=0.4) between infertile patients with endometriosis and controls (p=0.4), regardless of the stage of the disease. In relation to infertility, no statistically significant difference in the genotype or allele distribution (p=1.0 and p=0.9, respectively) was observed between idiopathic infertile women and controls. Considering the dominant inheritance model, again, no statistically significant difference was found even in the endometriosis (p=0.5) or the idiopathic infertility group (p=0.9) when compared to controls. Regarding the recessive inheritance model no statistically significant difference was found, with p=0.6 and p=1.0, respectively, for the endometriosis and idiopathic infertility groups...