BRAF polymorphisms and the risk of ovarian cancer of low malignant potential

OBJECTIVE: The object of this study was to test the hypothesis that BRAF is a low-risk susceptibility gene for low malignant potential (LMP) ovarian cancer. A recent study of the relationship between BRAF polymorphisms and malignant melanoma identified strong linkage disequilibrium across the BRAF gene with one of the three most common haplotypes (haplotype C) having a population attributable risk of approximately 1.6%. We therefore hypothesized that the same BRAF haplotype may confer an increased risk of serous ovarian tumors of low malignant potential. METHODS: We genotyped 383 cases of LMP ovarian cancer, including 234 of serous histology, and 987 controls for seven SNPs, representative of the most common BRAF gene haplotypes, using MALDI-TOF mass spectrometry. RESULTS: Haplotype information was obtained for 369 LMP ovarian cancer cases and 983 healthy controls. None of the haplotypes were found to be associated with risk of LMP ovarian cancer (OR for haplotype C 0.81, 95% CI = 0.54-1.22), or with the risk of serous LMP ovarian cancer (OR for haplotype C 0.90, 95% CI = 0.56-1.45). CONCLUSION: We found no evidence to suggest that BRAF is a low-risk LMP ovarian cancer susceptibility gene.     

Analysis of clinical trials in gynecologic cancer—Timing and interpretation

When and how often a clinical trial is analyzed is as important as the use of appropriate methodology. Premature analysis may result in inaccurate estimation of tumor response and adverse effects as well as misrepresentation of survival. Moreover, bias may be introduced or the study may be abandoned entirely. Of parallel importance to the timing is the emphasis given to the analyses. If a randomized comparative trial of two regimens is conducted and a significant therapeutic effect is not discerned, the study is generally classified as a negative study. This view is oversimplified; the negative conclusion drawn must have a much more limited scope than is generally appreciated. Lastly, the pitfalls of interpreting time variable curves such as survival are of special note. Quite often the "tails" of the curves totally belie the true implications of the analysis.     

The role of laparoscopy in ovarian tumors of low malignant potential and early-stage ovarian cancer

Although it is feasible today to perform laparoscopic surgical staging and treatment of ovarian low malignant potential tumors and early-stage ovarian cancer safely, it is still generally agreed that a patient with ovarian cancer should have a laparotomy. Concerns related to laparoscopy in managing gynecologic malignancy include the accuracy of intraoperative diagnosis, inadequate resection, significance of tumor spillage, improper or delay in surgical staging, delay in therapy, and the possibility of port-site metastasis. On the other hand, laparoscopy has the advantages of being a minimally invasive surgery, with shorter hospitalization, decreased postoperative pain, and quicker return to normal daily activities. We review the current literature discussing the consequences of laparoscopic surgery in ovarian tumors of low malignant potential and early-stage ovarian cancer. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to list the concerns related to laparoscopic management of ovarian malignancies, to outline the accuracy of the diagnosis of low malignant potential (LMP) ovarian tumors on frozen section, and to summarize the data on the effect of capsule rupture on overall prognosis for patients with ovarian cancer.     

The effect of polymorphisms in PD-1 gene on the risk of epithelial ovarian cancer and patients' outcomes

Objective

Programmed death-1 (PD-1), an important immunosuppressive molecule, plays a key role in tumor-cell-mediated immune escape. In the present study, we evaluated the effect of PD-1 gene polymorphisms on the risk of developing epithelial ovarian cancer (EOC) and patients' outcomes.

Preterm birth and inflammation—The role of genetic polymorphisms

Spontaneous preterm labour and preterm births are still the leading cause of perinatal morbidity and mortality in the developed world. Previous efforts to prevent preterm birth have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools and generally ineffective therapies.     

Vascular endothelial growth factor −2578 A/C, −460 T/C and +405 G/C polymorphisms in polycystic ovary syndrome

Objective

Vascular endothelial growth factor (VEGF) may be involved in the physiological regulation of ovarian angiogenesis and pathogenesis of polycystic ovary syndrome (PCOS). VEGF −2578 A/C, −460 T/C and +405 G/C single nucleotide polymorphisms (SNPs) are known to be related to VEGF production.

Study design

In order to investigate the possible association between VEGF gene and PCOS susceptibility, we analyzed genotype and allele distributions of above mentioned SNPs in 137 patients with PCOS and 155 healthy women. Differences in genotype distributions and allele frequencies in the cases and controls were compared for statistical significance using the χ²-test. Haplotype frequencies were estimated using a contingency χ²-test. Mann–Whitney U test was used for the statistics of the clinical and biochemical parameters.

Results

No significant association between PCOS and the variant alleles of VEGF −2578 (OR: 0.91, 95% CI = 0.65–1.26), −460 (OR: 0.78, 95% CI = 0.56–1.08), and +405 (OR: 1.25, 95% CI = 0.81–1.93) was observed. However, haplotype analysis demonstrated that the frequency of CTG haplotype, was higher among PCOS compared with controls (p = 0.019) and that there is a strong linkage disequilibrium (D′ = 0.873, r² = 0.752) between −2578 and −460 polymorphisms.

Conclusions

These preliminary results suggest that the −2578, −460 and +405 SNPs of VEGF gene are not significant risk factors for PCOS development alone. However, because of the high VEGF producer CTG haplotype was more frequent among the PCOS, we suppose that investigated polymorphisms – interacting with other genetic and environmental factors – could play a role in the development of PCOS.     

The role of cytoreduction in ovarian cancer

Whether or not cytoreduction improves the outlook of ovarian cancer patients is not yet clear from data from Literature. Maybe not the successful procedure itself, but the favourable tumor characteristics of these tumors determine the prognosis. New studies are necessary to define the role of surgery in the overall management of ovarian cancer more precisely. In this article a Dutch study is presented, to answer the question about the influence of attempted cytoreductive surgery prior to, during chemotherapy on survival time and remission rates. All patients are treated with either combination chemotherapy and/or an attempt to cytoreduction prior to or during chemotherapy. With this strategy ethical problems concerning undertreatment are avoided. The study is currently activated but it is too early to draw any conclusions.     

FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs

Purpose: To examine the frequency distribution of the Ser680Asn polymorphism of the follicle-stimulating hormone receptor (FSHR) gene in ovarian dysfunction (OD) infertile women, “poor responders” (PR) and “good responders” (GR). Methods: The hormonal profiles and treatment of all patients were analyzed and FSHR polymorphism was examined by PCR and RFLP. Women from all groups were classified as Asn/Asn, Asn/Ser, and Ser/Ser genotypes. Results: The frequency distribution of Ser/Ser, Asn/Ser and Asn/Asn variants in OD patients was 45.5, 22.7, and 31.8%, respectively. Day 3 FSH levels in OD and GR patients were higher in Ser/Ser and Asn/Asn subgroups. Asn/Ser carriers from OD and GR groups provided more follicles and oocytes compared to other allelic variants. Conclusions: GR patients carry more often the Asn/Ser genotype. The latter is correlated with more follicles and oocytes in both OD and GR patients. The Ser/Ser variant might be related to higher serum FSH levels, while the Asn/Ser with lower.     

The role of prostaglandins in ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome was produced in the rabbit by administration of human menopausal gonadotropins. It was shown that this syndrome can be prevented by indomethacin, a blocker of prostaglandin biosynthesis. The role of prostaglandins in the pathogenesis of ovarian hyperstimulation syndrome is discussed and the morphological changes in the ovaries due to treatment with HMG and indomethacin are demonstrated.     

The role of cytokines in polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Inflammation has been implicated in the metabolic disturbances and menstrual irregularities, which characterize this condition. Various inflammatory proteins have been investigated in women with PCOS including C-reactive protein, interleukin-6, interleukin-18 and tumor necrosis factor-alpha. The data is suggestive of the presence of a chronic low-grade inflammatory state, especially in case of obesity, insulin resistance and hyperandrogenism. Targeting this inflammatory process by means of anti-inflammatory agents might be a therapeutic alternative to the current treatment.     

The role of tumour markers in ovarian cancer

In the present review, the Authors have evaluated the current status of the utilization of the principle tumor markers for ovarian carcinoma in clinical gynecological practice. The major difficulty in individualizing a single marker is represented by the histological differentiation of the tumor itself. In fact, whereas for the malignant germ cell tumors, useful markers (AFP, B-HCG) are already available, for other histological forms, valid markers have been identified only because of the availability of the monoclonal antibody: CA 125. Even if this marker cannot be proposed for mass screening, it represents a useful instrument for the diagnosis and monitoring of ovarian carcinoma. The serum levels are well correlated with the clinical status of the patient and high concentrations of the marker are strongly indicative of disease progression at the second-look. Numerous other markers such as NB 70K, IAP, PLAP, CA 15-3 and TAG 72, are actually in the clinical evaluation phase, for the most part in association with CA 125.     

The potential role of high or low birthweight as risk factor for adult schizophrenia

OBJECTIVE: Obstetric complications may be an important factor in the development of schizophrenia. The aim of this study is to evaluate the role of these complications in the development of schizophrenia in adult life, with particular attention to the potential role of birth weight. METHOD: We carried out a case-control study, comprising schizophrenics and patients with diseases of the schizophrenia spectrum as cases, and their healthy male brothers as controls. Obstetric complications were assessed using the "Midwife Protocol" of Parnas et al. RESULTS: The main result was that birth weight may be a risk factor for schizophrenia, as indicated by odds ratio analysis. The confidence intervals are very wide and, without compromising the clinical significance of the results, they give a limited indication of the real entity of the risk. CONCLUSIONS: The results contribute to understanding of the role played by a single complications.