Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers.

BRCA1 mutations substantially elevate the risks of breast and ovarian cancer. Various modifiers, including environmental factors, can influence cancer risk. Lead, a known carcinogen, has been associated with various cancers, but its impact on BRCA1 carriers remains unexplored. A cohort of 989 BRCA1 mutation carriers underwent genetic testing at the Pomeranian Medical University, Poland. Blood lead levels were measured using inductively coupled plasma mass spectrometry. Each subject was assigned to a category based on their tertile of blood lead. Cox regression analysis was used to assess cancer risk associations. Elevated blood lead levels (>13.6 µg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23-9.00; p = 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01; p = 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.

Zinc and Its Antioxidant Properties: The Potential Use of Blood Zinc Levels as a Marker of Cancer Risk in BRCA1 Mutation Carriers.

BRCA1 mutations predispose women to breast and ovarian cancer. The anticancer effect of zinc is typically linked to its antioxidant abilities and protecting cells against oxidative stress. Zinc regulates key processes in cancer development, including DNA repair, gene expression, and apoptosis. We took a blood sample from 989 female BRCA1 mutation carriers who were initially unaffected by cancer and followed them for a mean of 7.5 years thereafter. There were 172 incident cases of cancer, including 121 cases of breast cancer, 29 cases of ovarian cancers, and 22 cancers at other sites. A zinc level in the lowest tertile was associated with a modestly higher risk of ovarian cancer compared to women with zinc levels in the upper two tertiles (HR = 1.65; 95% CI 0.80 to 3.44; p = 0.18), but this was not significant. Among those women with zinc levels in the lowest tertile, the 10-year cumulative risk of ovarian cancer was 6.1%. Among those in the top two tertiles of zinc level, the ten-year cumulative risk of ovarian cancer was 4.7%. There was no significant association between zinc level and breast cancer risk. Our preliminary study does not support an association between serum zinc level and cancer risk in BRCA1 mutation carriers.

Epithelial Ovarian Cancer-Varied Treatment Results.

Ovarian cancer (OC) is the eighth most common cancer worldwide and is usually diagnosed in advanced stages. Despite many available data, no treatment results have been reviewed in Poland. This study enrolled 289 first-time patients treated between 2018 and 2021 by the Department of Oncology of the Poznan University of Medical Sciences (SKPP). The relationships among starting treatment in our centre, the type of first intervention, and the final decision were significant (p < 0.001). Patients in the SKPP group were more likely to primarily have a laparoscopy and less likely to have an exploratory laparotomy. Neoadjuvant chemotherapy (NACT) after a laparotomy was less often a final decision among SKPP patients (9% vs. 22%), in contrary to NACT after a laparoscopy (23% vs. 4%). Factors affecting the shortening of progression-free survival (PFS) were an advanced stage of the disease, a histopathological diagnosis, the type of cytoreduction, and the final decision. Significance according to the final decision was revealed for PDS vs. NACT after a laparotomy (p < 0.001) and for PDS vs. NACT after a laparoscopy (p = 0.011). Our study supports the benefits of treating ovarian cancer in an oncology centre with a high patient throughput. Further observations might also answer the question about overall survival (OS).

High-Volume Hospitals' Ovarian Cancer Care-Less Individual Approach or Better Treatment Results?

Ovarian cancer (OC) is the eighth most common cancer worldwide and is usually diagnosed in advanced stages. The relationship between treatment in high-volume hospitals (HVHs) and survival in OC has been documented by multiple studies, which showed that superior treatment and survival outcomes are associated with surgical expertise and multidisciplinary resources. To our study, 135 first-time patients treated in the years 2019-2020 in the Department of Oncology of Poznan University of Medical Sciences were enrolled. Th analysis showed a significant dependency between being treated in a HVH from the beginning of one's diagnosis and the scope of the first intervention. Additionally, among patients treated in our centre, a significant portion of patients underwent laparoscopy, and from one year to another the number of laparoscopies performed increased. This may indicate that more patients began to qualify for neoadjuvant treatment. Patients benefit the most from surgery in a centre with more experience in treating ovarian cancer. In the future, we will be able to expand this study by using data from patients treated before 2019 and analysing larger cohorts of patients. This might enable us to update the rates of overall survival (OS), objective response rate (ORR) and progression-free survival (PFS).

Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer.

The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in BRCA1 (9 mutations), BRCA2 (4 mutations), RAD51C (3 mutations), PALB2 (2 mutations), and CHEK2 (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in BRCA1 (OR = 40.79, 95% CI: 18.67-114.78; p = 0.29 × 10-15), in BRCA2 (OR = 25.98; 95% CI: 1.55-434.8; p = 0.001), in RAD51C (OR = 6.28; 95% CI 1.77-39.9; p = 0.02), and in PALB2 (OR 3.34; 95% CI: 1.06-14.68; p = 0.06). There was no association found for CHEK2. We found that pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.