Objectives: The aim of the study was to examine the overall risk factors for epithelial ovarian cancer and according to histologic subtypes. Materials and Methods: Ovarian cancer cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. A total of 554 cases and 1,564 randomly selected controls were included. The analyses were done using multiple logistic regression models. Results: The overall risk of ovarian cancer decreased with ever being pregnant [odds ratios (OR), 0.40; 95% confidence intervals (CI), 0.30-0.55], with increasing pregnancies (OR, 0.63; 95% CI, 0.45-0.87 and OR, 0.51; 95% CI, 0.37-0.69 for two and three pregnancies as compared with one), and with older age at first and last pregnancy, respectively. Increasing years of ovulation was a very strong risk factor with a 7% to 8% increase in risk for each year of ovulation. Use of oral contraceptives (OR, 0.67, 95% CI, 0.53-0.85) and longer duration of use were associated with a decreased risk of ovarian cancer. Ever use of hormone replacement therapy increased the overall risk (OR, 1.30; 95% CI, 1.05-1.61). For all those variables, the effect was present for serous tumors, endometrioid tumors, and tumors of other histologies, but not for mucinous tumors. In contrast, current smoking was a risk factor only for mucinous tumors (OR, 1.78; 95% CI, 1.01-3.15) and increasing body mass index tended to increase the risk especially for mucinous and endometrioid tumors. Conclusions: We confirmed already known risk factors for ovarian cancer, and we observed significant differences in the risk profiles between mucinous and nonmucinous tumors indicating different etiologies. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1160 -6)

Purpose:To evaluate the prevalence of BRCA1and BRCA2 mutations and associations with clinical correlates of disease in a population-based series of ovarian cancer cases from Denmark. Methods: DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze the BRCA1 and BRCA2 genes for coding sequence mutations and large genomic rearrangements in 445 confirmed cases of ovarian cancer. We evaluated associations between mutation status and clinical characteristics, including cancer risks for first-degree relatives and clinicopathologic features of tumors. Results: Deleterious BRCA1 or BRCA2 mutations were identified in 26 cases; thus, mutations in these genes are responsible for at least 5.8% of ovarian cancer cases in this population. Five different mutations were identified in more than one individual, suggesting that they may be founder mutations in Denmark. We identified several differences between mutation carriers and noncarriers: mutation carriers were diagnosed at a significantly early age (median, 49 and 61 years, respectively; P = 0.0001); the frequency of BRCA1 mutation carriers was 23% for women diagnosed <40 years,15% for 40 to 49 years, 4% for 50 to 59 years, and 2% for z60 years (P = 0.00002); ovarian cancer in carriers was diagnosed at a later stage (P = 0.002) and tumors were of poorer grade (P = 0.0001); and first-degree relatives of mutation carriers had greater relative risks of both ovarian cancer [10.6 (95% confidence interval, 4.2-26.6); P < 0.0001] and breast cancer <60 years [8.7 (95% confidence interval, 3.0-25.0); P < 0.0001].Conclusion: These data may have a significant effect on risk assessment and clinical management of individuals from Denmark who are predisposed to ovarian cancer because they carry a BRCA1 or BRCA2 mutation.

Cancer diagnoses in first-degree relatives are not always accurately reported by patients with ovarian cancer or by controls. The results indicate that studies of associations with family cancer history should validate self-reported family cancer diagnoses as carefully as possible.

Ovarian cancer in a first-degree relative is a very strong predictor of epithelial ovarian cancer, especially early-onset ovarian cancer. Ovarian cancer in first-degree relatives seems to be positively associated with especially non-mucinous tumors.

Background Diastolic dysfunction (DD) in heart failure (HF) is associated with increased myocardial cytosolic calcium, and calcium-efflux via the sodium-calcium-exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR)-agonist lowers cytosolic sodium and has been shown to reverse organ congestion. Purpose To assess whether β3-AR-agonist treatment improves DD. Methods In a first-in-man randomized controlled, double-blind trial, we assigned 70 patients with HF with reduced ejection fraction (HFrEF) (NYHA II–III) and LVEF &lt;40% to receive mirabegron (300 mg/day) or placebo for 6 months, in addition to recommended HF-therapy. Patients were assessed with echocardiography and cardiac computed tomography (CCT) at baseline and follow-up. DD was graded according to the current American/European guidelines. Results Baseline and follow-up echocardiographic data were available in 57 patients (59±11 years, 88% male, 49% ischemic heart disease). Baseline LVEF was 34%±8%. No significant change in DD grade was found between the groups at follow-up, p=0.72. Neither was there any clinical differences in any singular diastolic parameters within or between groups by echocardiography (E/e' placebo: 13.3±6.9 to 12.6±5.1, p=0.19 vs. mirabegron: 12.0±5.7 to 12.8±7.9, p=0.67, mean difference 1.12 [95% CI −1.68 to 4.3], p=0.37), or CCT (left atrial max volume index: between group mean difference 0.2 [95% CI −6.2 to 5.6] ml/m2, p=0.91). Conclusions In patients with HFrEF, no improvement nor worsening in DD gradings or singular diastolic parameters after β3-AR stimulation compared to placebo were identified. The findings add to previous literature questioning the role of impaired Na+-Ca2+ mediated Ca2+ export as a major culprit in DD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Heart Centre Research Foundation, RigshospitaletThe Novo Nordic Foundation