BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case–control study

Abstract

The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case -control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR ¼ 29, 95% CI ¼ 6.6 -120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.

Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

“…A third of patients diagnosed with BOTs are younger than 40 years of age and frequently are candidates for fertility-sparing surgery [3,10]. Borderline tumors are rarely seen in women with BRCA mutations [16]. Although a few cases of BOTs have been reported in BRCA mutation carriers, it rather reflects the prevalence of these mutations in the general population.…”

Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case–Control Study

“…The samples were stored at À25 C for up to 40 years. The samples were genotyped by means of cycling temperature capillary electrophoresis (23), a PCR-based method that has successfully been applied in previous projects investigating Janus serum samples (24,32). Because the DNA is expected to be degraded, we applied a primer design that yielded short amplicons (<100 bases).…”

Mesothelin-related predictive and prognostic factors in malignant mesothelioma: A nested case–control study

“…CYFRA 21-1 can also be elevated in various epithelial cancers [29][30][31] and CA125 may be elevated in various adenocarcinomas [32,33], non-Hodgkin lymphoma [34] as well as in non-malignant conditions affecting the mesothelium, such as pleuritis, pericarditis, peritonitis and in other conditions, such as chirrosis, endometriosis, tuboovarial abscesses and benign and borderline ovarian tumors [35] and chronic congestive heart failure [36].…”