Blood molybdenum level as a marker of cancer risk on BRCA1 carriers.

OBJECTIVE: To investigate whether Molybdenum blood level is a marker of cancer risk on BRCA1 carriers. METHODS: A prospective cohort study was conducted among 989 initially unaffected women with a BRCA1 mutation. Blood samples were collected to measure molybdenum levels, and participants were followed for an average of 7.5 years. Cox proportional hazards models were used to assess the association between blood molybdenum levels and cancer incidence, adjusting for potential confounders. RESULTS: High blood molybdenum levels (> 0.70 µg/L) were significantly associated with an increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59-19.4; p = 0.007) and any cancer (HR = 1.74; 95%CI: 1.17-2.61; p = 0.007) but not breast cancer (HR = 1.46, CI = 0.91-2.33; p = 0.12). The cumulative incidence of ovarian cancer at ten years was 1.2% for the lowest molybdenum tertile, 4.2% for the middle tertile, and 8.7% for the highest tertile. CONCLUSION: Elevated blood molybdenum levels are associated with an increased risk of ovarian cancer on BRCA1 mutation carriers. Lowering molybdenum levels may potentially reduce cancer risk in this population, and high molybdenum levels could serve as a marker for considering preventive oophorectomy in BRCA1 carriers. Further research is warranted to confirm these findings and explore interventions targeting molybdenum levels as a preventive measure for ovarian cancer in BRCA1 mutation carriers.

Pro/antioxidant status and selenium, zinc and arsenic concentration in patients with bipolar disorder treated with lithium and valproic acid.

Disturbances in pro/antioxidant balance emerge as a crucial element in bipolar disorder (BD). Some studies suggest that treatment effects on trace element concentration in BD. This study aimed to identify (a) the changes related to oxidative stress in BD and their relationship with trace elements engaged in pro/antioxidant homeostasis; (b) BD biomarkers using machine learning algorithm classification and regression tree (C&RT) analysis. 62 individuals with BD and 40 healthy individuals (HC) were included in the study. The concentration of pro/antioxidant state and concentration of selenium, zinc, arsenic in blood were assessed. We found a higher concentration of total antioxidant capacity, catalase, advanced oxidation protein products and a lower concentration of 4-hydroxynonenal (4-HNE), glutathione, glutathione peroxidase (GPx) in BD compared to HC. All examined trace elements were lower in the BD group compared to HC. A combination of two variables, 4-HNE (cut-off: ≤ 0.004 uM/mg protein) and GPx (cut-off: ≤ 0.485 U/mg protein), was the most promising markers for separating the BD from the HC. The area under the receiver operating characteristic curve values for C&RT was 90.5%. Disturbances in the pro/antioxidant state and concentration of trace elements of patients with BD may be a target for new therapeutic or diagnostic opportunity of BD biomarkers.

Blood and Serum Se and Zn Levels and 10-Year Survival of Patients after a Diagnosis of Kidney Cancer.

The aim of the project was to evaluate the association between selenium (Se) and zinc (Zn) levels in blood and serum and kidney cancer mortality. In a prospective group of 284 consecutive, unselected patients with kidney cancer, we evaluated their 10-year survival rate in relation to the levels of Se and Zn in their blood and serum. Micronutrient levels were measured using an inductively coupled plasma mass spectrometer. Patients were divided into quartiles based on the distribution of Se and Zn levels arranged in increasing order. The following variables were taken into account in the multivariable models: age at diagnosis, gender, smoking, type of surgery and histopathological examination results. We observed a statistically significant association of all-cause mortality when subgroups with low blood selenium levels were compared to patients with high selenium levels (HR = 7.74; p < 0.001). We found, in addition, that this correlation was much stronger when only men were assessed (HR = 11.6; p < 0.001). We did not find a statistically significant association for zinc alone. When we combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV), we observed the hazard ratio for kidney cancer death to be 12.4; p = 0.016. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR was 2.53; p = 0.008. Our study suggests that selenium levels, combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV) and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients.

Cobalt Serum Level as a Biomarker of Cause-Specific Survival among Prostate Cancer Patients.

Prostate cancer is the most common cancer diagnosed in men and the second leading cause of death in male cancer patients. The WHO suggests that cobalt is involved in the carcinogenesis of prostate cancer. There are, however, no studies associating cobalt levels and prostate cancer patient survival. In this study, 261 Polish prostate cancer (n = 261) patients were recruited into a prospective cohort between 2009 and 2015. Serum cobalt levels were measured using ICP-MS after prostate cancer diagnosis and before treatment. All study participants were assigned into quartiles (QI-QIV) based on the distribution of serum cobalt levels among censored patients. Univariable and multivariable COX regression models were used to calculate hazard ratios (HRs) for each serum cobalt level quartile. We found a significant relationship between high serum cobalt levels and poor prostate cancer patient total survival (HR = 2.60; 95% CI: 1.17-5.82; p = 0.02). In relation to prostate cancer patients who died as a result of other non-cancer causes, the association with high levels of cobalt was even stronger (HR = 3.67; 95% CI: 1.03-13.00; p = 0.04). The impact of high serum cobalt levels on overall survival of prostate cancer-specific-related deaths was not statistically significant.

Antioxidant Properties of Zinc and Copper-Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers.

Pathogenic mutations in BRCA1 (BReast CAncer gene 1) confer high risks of both breast (up to 70%) and ovarian (up to 40%) cancers. Zinc (Zn) and copper (Cu) are essential for various physiological functions, including antioxidant reactions. Their balance, reflected in the Zn/Cu ratio, plays a crucial role in maintaining redox homeostasis, which is vital for cancer prevention. This study examines the antioxidant properties of Zn and Cu, specifically focusing on the blood Zn/Cu ratio as a potential marker for cancer risk among BRCA1 mutation carriers. The study cohort consisted of 989 initially unaffected women, followed up for 7.5 years. Blood samples were analyzed using inductively coupled plasma mass spectrometry. Although individual Zn and Cu levels did not significantly correlate with overall cancer risk, those women with a Zn/Cu ratio above 6.38 experienced a significantly lower cancer risk than women with a ratio below this cut-off point. This suggests that the Zn/Cu ratio may be a valuable biomarker for cancer prevention in this high-risk group. Given the increased cancer risk in BRCA1 mutation carriers, optimizing Zn and Cu levels through dietary and active interventions could provide a preventive strategy.

Blood Iodine as a Potential Marker of the Risk of Cancer in BRCA1 Carriers.

Breast cancer and ovarian cancer pose a significant risk for BRCA1 carriers, with limited risk-reduction strategies. While improved screening helps in the early detection of breast cancer, preventive measures remain elusive. Emerging evidence suggests a potential link between iodine levels and modulation of cancer risk, but comprehensive studies are scarce. We conducted a prospective study among 989 BRCA1 carriers to assess the association between blood iodine levels and breast and ovarian cancer risk. Using inductively coupled plasma mass spectrometry, we measured blood iodine levels and observed a negative association with breast cancer risk, with a significantly lower risk observed in quartile 4 (iodine > 38.0 µg/L) compared with quartile 1 (iodine < 30 µg/L) (HR = 0.49; 95%CI: 0.27-0.87; p = 0.01). Conversely, a suggestive increase in ovarian cancer risk was observed at higher iodine levels (HR = 1.91; 95%CI: 0.64-5.67; p = 0.25). No significant association was found between iodine levels and overall cancer risk. Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy but require further validation and investigation of its effect on ovarian cancer risk and overall mortality. These findings highlight the need for personalized strategies to manage cancer risk in BRCA1 carriers.

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.

Correlation between Selenium and Zinc Levels and Survival among Prostate Cancer Patients.

The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.

Serum Essential Elements and Survival after Cancer Diagnosis.

In a prospective study, we measured the associations between three serum elements (Se, Zn and Cu) and the prognosis of 1475 patients with four different types of cancer (breast, prostate, lung and larynx) from University Hospitals in Szczecin, Poland. The elements were measured in serum taken after diagnosis and prior to treatment. Patients were followed from the date of diagnosis until death from any cause or until the last follow-up date (mean years of follow-up: 6.0-9.8 years, according to site). Kaplan-Meier curves were constructed for all cancers combined and for each cancer separately. Age-adjusted hazard ratios (HRs) were estimated using Cox regression. The outcome was all-cause mortality. A Se level in the highest quartile was also associated with a reduced mortality (HR = 0.66; 95%CI 0.49-0.88; p = 0.005) in all-cause mortality for all cancers combined. Zn level in the highest quartile was also associated with reduced mortality (HR = 0.55; 95%CI 0.41-0.75; p = 0.0001). In contrast, a Cu level in the highest quartile was associated with an increase in mortality (HR = 1.91; 95%CI 1.56-2.08; p = 0.0001). Three serum elements-selenium, zinc and copper-are associated with the prognosis of different types of cancer.

Surgical Approach in Metastatic Renal Cell Carcinoma: A Literature Review.

The treatment of metastatic renal cell carcinoma has undergone considerable advances in the last two decades. Cytoreductive nephrectomy and metastasectomy retains a role in patients with a limited metastatic burden. The choice of optimal treatment regimen remains a matter of debate. The article summarises the current role of surgery in metastatic kidney cancer.

The Role of Focal Therapy and Active Surveillance for Small Renal Mass Therapy.

Small and low-grade renal cell carcinomas have little potential for metastasis and disease-related mortality. As a consequence, the main problem remains the use of appropriately tailored treatment for each individual patient. Surgery still remains the gold standard, but many clinicians are questioning this approach and present the advantages of focal therapy. The choice of treatment regimen remains a matter of debate. This article summarizes the current treatment options in the management of small renal masses.

A Liquid Biopsy in Bladder Cancer-The Current Landscape in Urinary Biomarkers.

The non-muscle invasive bladder cancer tends to recur and progress. Therefore, it requires frequent follow-ups, generating costs and making it one of the most expensive neoplasms. Considering the expensive and invasive character of the current gold-standard diagnostic procedure, white-light cystoscopy, efforts to find an alternative method are ongoing. Although the last decade has seen significant advancements in urinary biomarker tests (UBTs) for bladder cancer, international guidelines have not recommended them. Currently, the paramount urgency is to find and validate the test with the best specificity and sensitivity, which would allow for the optimizing of diagnosis, prognosis, and a treatment plan. This review aims to summarise the up-to-date state of knowledge relating to UBTs and new developments in the detection, prognosis, and surveillance of bladder cancer and their potential applications in clinical practice.

Prostate Cancer Liquid Biopsy Biomarkers' Clinical Utility in Diagnosis and Prognosis.

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker's low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers.

The high occurrence of bladder cancer and its tendency to recur in combination with a lifelong surveillance make the treatment of superficial bladder cancer one of the most expensive and time-consuming. Moreover, carcinoma in situ often leads to muscle invasion with an unfavorable prognosis. Currently, invasive methods including cystoscopy and cytology remain a gold standard. The aim of this study was to explore urine-based biomarkers to find the one with the best specificity and sensitivity, which would allow optimizing the treatment plan. In this review, we sum up the current knowledge about Cytokeratin fragments (CYFRA 21.1), Excision Repair Cross-Complementation 1 (ERCC1), Tumour Protein p53 (Tp53), Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor-Associated Trypsin Inhibitor (TATI) and their potential applications in clinical practice.