ABSTRACT
PURPOSE: Ovarian cancer ranks 6th in relation to new cases of malignant diseases among females and 2nd concerning gynecological cancers. The purpose of this study was to determine the epidemiological situation of ovarian cancer in Vojvodina, Serbia. METHODS: In our study, we used a descriptive epidemiological method for the analysis of incidence and mortality of ovarian cancer in Vojvodina, based on the data of the Cancer Registry of Vojvodina. RESULTS: In the period 1987-2006, the average incidence rate of ovarian cancer was 15.28%/100,000 with an average annual increase of 1.15%; the average mortality rate for the same period was 9.24/100,000 with an average annual increase of 0.95%. The values of crude incidence rate (15.28/100,000) and standardized incidence rate (range 7.47 - 12.55/100,000) in Vojvodina correspond to the values in eastern and southern Europe. CONCLUSION: In the observed period of 20 years, the incidence and mortality rate indicate a tendency for increase, which can be characterized as an unfavorable epidemiological situation. New markers are being studied in order to find a solution for ovarian cancer screening.
Subject(s)
Ovarian Neoplasms/epidemiology , Adult , Age Factors , Aged , Female , Humans , Incidence , Middle Aged , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Registries , Yugoslavia/epidemiologyABSTRACT
The lymphoid tyrosine phosphatase (LYP), encoded by the protein tyrosine phosphatase-22 (PTPN22) gene, is a powerful inhibitor of T cell activation. Recently, a single nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at LYP codon 620 has been shown to be associated with type 1 diabetes and other autoimmune disorders. We have used a PCR-restriction fragment (XcmI) assay to examine genotypes at the codon 620 polymorphism in 549 unrelated probands with Graves' disease, 104 unrelated subjects with autoimmune Addison's disease and 429 controls. The T nucleotide at the SNP, encoding the tryptophan 620 residue, was present in 151 of 1098 (13.8%) Graves' disease alleles compared to 67 of 858 (7.8%) control alleles (chi(2) = 17.2, p = 3.4 x 10(-5)' odds ratio = 1.88, 5-95% confidence intervals [CI] 1.39 to 2.55). Similarly, the T nucleotide at the codon 620 SNP was present in 26 of 208 (12.5%) Addison's disease alleles vs 7.8% of controls (chi(2) = 4.63, p = 0.031; odds ratio = 1.69, 5-95% CI 1.04 to 2.73). These data suggest that this LYP polymorphism is a susceptibility allele for Graves' disease with a major effect, and which is likely to have a role in many other autoimmune conditions.
Subject(s)
Alleles , Codon , Graves Disease/genetics , Lymphocytes/enzymology , Polymorphism, Single Nucleotide , Protein Tyrosine Phosphatases/genetics , Addison Disease/genetics , Humans , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Tryptophan/geneticsABSTRACT
Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign.
Subject(s)
Ecchymosis/etiology , Hypothyroidism/complications , Ovarian Hyperstimulation Syndrome/etiology , Puberty, Precocious/complications , Receptors, FSH/genetics , Adolescent , Diagnosis, Differential , Ecchymosis/diagnostic imaging , Ecchymosis/metabolism , Female , Follicle Stimulating Hormone/metabolism , Humans , Hypothyroidism/diagnostic imaging , Ovarian Hyperstimulation Syndrome/diagnostic imaging , Ovarian Hyperstimulation Syndrome/metabolism , Ovary/diagnostic imaging , Puberty, Precocious/diagnostic imaging , Puberty, Precocious/metabolism , Receptors, FSH/metabolism , Sequence Analysis, DNA , Time Factors , Ultrasonography , UmbilicusABSTRACT
BACKGROUND: Macroorchidism in prepuberty is an uncommon condition which we hypothesised might reflect constitutive activation of the FSH receptor (FSHR). PATIENTS AND METHODS: Patient 1 was found to have macroorchidism (15 ml testicular volume) at the time of orchidopexy when 3.7 years of age. A gonadal biopsy was obtained at the time of surgery. Patient 2 developed macroorchidism (5 ml) when 8.8 years old. Despite a testicular volume >4 ml, morning testosterone levels were unrecordable with no measurable gonadotrophin production in either patient. Patient 2 had prepubertal gonadotrophin levels 3 years later despite a testicular volume that was 8 ml bilaterally. Inhibin B was measured and the FSHR sequenced in both patients. RESULTS: Inhibin B levels were age and pubertal stage appropriate. Gonadal biopsy (patient 1) demonstrated areas of Sertoli cell hyperplasia. Sequence analysis of all 10 exons of the FSHR was normal. There was significant, presumed gonadotrophin-dependent testosterone production in both boys by 15 years of age. CONCLUSIONS: The cause of prepubertal macroorchidism in our patients is unclear but the pronounced difference in phenotype suggests that there may be more than one underlying mechanism. This mechanism was not constitutive activation of a mutated FSHR.