RESUMEN
A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland.
Asunto(s)
Genes BRCA1 , Genes BRCA2 , Mutación/genética , Neoplasias Ováricas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , ADN de Neoplasias/análisis , Femenino , Genotipo , Humanos , Islandia/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Neoplasias Ováricas/epidemiología , LinajeRESUMEN
Ovarian cancer causes more deaths than any other gynecologic malignancy in developed countries. Sixteen million sequence variants, identified through whole-genome sequencing of 457 Icelanders, were imputed to 41,675 Icelanders genotyped using SNP chips, as well as to their relatives. Sequence variants were tested for association with ovarian cancer (N of affected individuals = 656). We discovered a rare (0.41% allelic frequency) frameshift mutation, c.2040_2041insTT, in the BRIP1 (FANCJ) gene that confers an increase in ovarian cancer risk (odds ratio (OR) = 8.13, P = 2.8 × 10(-14)). The mutation was also associated with increased risk of cancer in general and reduced lifespan by 3.6 years. In a Spanish population, another frameshift mutation in BRIP1, c.1702_1703del, was seen in 2 out of 144 subjects with ovarian cancer and 1 out of 1,780 control subjects (P = 0.016). This allele was also associated with breast cancer (seen in 6/927 cases; P = 0.0079). Ovarian tumors from heterozygous carriers of the Icelandic mutation show loss of the wild-type allele, indicating that BRIP1 behaves like a classical tumor suppressor gene in ovarian cancer.
Asunto(s)
Proteínas de Unión al ADN/genética , Mutación , Neoplasias Ováricas/genética , ARN Helicasas/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi , Femenino , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Actinomycosis is an infectious disease that has been known since the late nineteenth century. In the pre-antibiotic era it was thought to be rather common but with increased use of antimicrobial agents its incidence has decreased significantly. The causative agent, most commonly Actinomyces israelii, is part of the commensal bacterial flora. It can infect any tissue, respects no tissue boundaries and can spread throughout the body. The clinical presentation of this illness can be similar to malignant disease and definite diagnosis is sometimes not apparent until after surgery and histologic examination. We report the case of a 71 year old woman who suffered from actinomycosis of the uterus and ovaries due to a forgotten intrauterine contraceptive device that had been in place for over four decades. The disease presentation was consistent with malignant disease and tumor markers, CA 125, CA 19-9 and CEA, measured in blood were elevated. She was treated successfully with total hysterectomy and bilateral salphingo-oophorectomy, as well as penicillin for six months.