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.

Risk of Second Primary Thyroid Cancer in Women with Breast Cancer.

The goal of this study was to estimate the risk of thyroid cancer following breast cancer and to identify therapeutic and genetic risk factors for the development of thyroid cancer after breast cancer. We followed 10,832 breast cancer patients for a mean of 14 years for new cases of thyroid cancer. All women were genotyped for three Polish founder mutations in BRCA1 (C61G, 4153delA, 5382insC) and four mutations in CHEK2 (1100delC, IVS2 + 1G/A, del5395, I157T). Information was collected on chemotherapy, radiotherapy, hormonal therapies, and oophorectomy. Of the 10,832 women, 53 (0.49%) developed a second primary thyroid cancer. Based on Polish population statistics, the expected number was 12.4 (SIR = 4.3). The ten-year risk of developing thyroid cancer was higher in women who carried a CHEK2 mutation (1.5%) than in women who carried no mutation (0.9%). The age-adjusted hazard ratio for developing thyroid cancer was 1.89 (0.46-7.79; p = 0.38) for those with a CHEK2 protein-truncating mutation and 2.75 (1.29-5.85; p = 0.009) for those with a CHEK2 missense mutation.

HbA1c Screening for Diabetes in Patients with Acute Coronary Syndrome: A Worthwhile Test or a Pitfall?

BACKGROUND: Diagnostic concordance between HbA1c and other glucose-based tests is imperfect, and data on this problem in acute coronary syndrome (ACS) are still lacking. The aim of this study was to identify undiagnosed glucose abnormalities in ACS patients, and to compare the effectiveness and consistency of the diagnostic screening based on HbA1c to the oral glucose tolerance test (OGTT). METHODS: The study group consisted of 121 ACS patients, mean age 62.3 ± 11.6 years, without known glucose abnormalities. HbA1c, admission and fasting plasma glucose in the first days of hospitalization were assessed and referred to the results of OGTT performed two weeks after discharge. RESULTS: OGTT identified normoglycemia in 45%, pre-diabetes in 39.4%, and diabetes in 15.6%, while HbA1c revealed these categories in 39.7%, 51.2%, and 9.1%, respectively. With an HbA1c cut-off ≥6.5% (48 mmol/mol) diagnostic for diabetes, the sensitivity of the method was 41%, while specificity was 98%, compared to the OGTT. The optimal HbA1c cut-off value at the crossing of sensitivity and specificity curves was 5.9%. The HbA1c value recommended for the diagnosis of pre-diabetes and optimal cut-off point were the same (5.7%). CONCLUSIONS: Using HbA1c without OGTT in an early but stable phase of ACS may result in a significant underdiagnosis of diabetes.

High-Protein or Low Glycemic Index Diet-Which Energy-Restricted Diet Is Better to Start a Weight Loss Program?

BACKGROUND: To date, no crossover studies have compared the effects of high-protein (HP) and low glycemic index (LGI) diets applied as starting energy-restricted diets. METHODS: Thirty-five overweight or obese volunteers with sedentary lifestyles aged 41.4 ± 11.0 years, with body mass index (BMI) of 33.6 ± 4.2 kg/m2, without diabetes, completed an 8-week randomized crossover study of an energy-restricted diet (reduction of 30%; approximately 600 kcal/day). The anthropometric parameters, body composition, 24 h blood pressure, and basic metabolic profile were measured at baseline and after completing the two 4-week diets; i.e., the HP (protein at 30% of the daily energy intake) or LGI diet, followed by the opposite diet. All subjects maintained food diaries and attended six counselling sessions with a clinical dietitian. RESULTS: The final weight loss was not significantly different when the HP diet was used first but was associated with a greater loss of fat mass: 4.6 kg (5.8; 3.0 kg) vs. 2.2 (4.5; 0.8); p < 0.025, preserved muscle mass, and reduced LDL-cholesterol. CONCLUSIONS: A short-term HP diet applied as a jump-start diet appeared to be more beneficial than an LGI diet, as indicated by the greater fat mass loss, preservation of muscle mass, and better effects on the lipid profile.

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes.

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single-cell transcriptomics, ribosome profiling, and two MS/MS search tools in combination. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides, including an immunogenic peptide derived from an open reading frame downstream of the melanoma stem cell marker gene ABCB5. These findings hold great promise for the discovery of previously unknown tumor antigens for cancer immunotherapy.

Assessment of diabetes control in insulin pump therapy in late adolescentsand young adults with type 1 diabetes.

OBJECTIVES: The aim of the study was to evaluate metabolic control in insulin pump therapy (IPT) in late adolescents and young adults with type 1 diabetes mellitus. MATERIAL AND METHODS: The study was conducted in 86 subjects with type 1 diabetes, and included 45 patients aged 16-19 years (mean 17.6±1.2) treated in a pediatric outpatient clinic and 41 subjects aged 19-26 years (mean 22.8±2.2) treated in an adult outpatient clinic of the same university hospital, who received the same refund of IPT. RESULTS: Late adolescents had a lower BMI (22.7±2.9 kg/m2 vs. 24.2±3.2 kg/m2; P<0.05), higher HbA1c (69.4±15.1 mmol/mol vs. 58.5±11.8 mmol/mol; P<0.001) and mean blood glucose levels (10.4±2.6 mmol/l vs. 9.2±1.4 mmol/l, P<0.05), and received higher insulin doses per day (0.85±0.23 IU/kg vs. 0.65±0.13 IU/kg; P<0.001). The mean diabetes and IPT duration, number of visits, basal/bolus insulin ratio, number of insulin boluses, blood glucose tests and the episodes of hypoglycemia were similar. CONCLUSIONS: Metabolic control in late adolescents with type 1 diabetes on IPT is significantly worse than in young adults, despite higher doses of insulin and very similar way of treatment and self-control. This may be related to the patients age or the less rigorous approach to therapeutic recommendations resulting from pediatric diabetes care.

Evaluation of Microfluidics-FISH method in prenatal diagnosis.

OBJECTIVES: Classical cytogenetic analysis remains a gold standard in invasive prenatal diagnosis. Recently, Microfluidics¬-FISH, a novel method based on FISH, has been introduced. This integral approach allows to obtain result for common aneuploidies within the same day from a much smaller sample of the amniotic fluid. In this study we compare effectiveness of Microfluidics-FISH to classical karyotype and Rapid FISH. MATERIAL AND METHODS: 52 samples of amniotic fluid were drawn from the pregnant women due to common indications. Cell cultures have been set up for classical cytogenetic analysis as well as amniotic cells have been loaded into the microchip of Microfluidics-FISH as well standard procedure of Rapid FISH was performed for evaluation of trisomy 21, 13, 18 chromosome and sex chromosomes numeric aberrations. RESULTS: 9 samples out of 52 showed chromosomal aberrations in both FISH methods what was consistent with karyoty¬ping. One case of small supernumerary marker chromosome was detected only in the classical cytogenetic analysis. For the majority of cases turnaround time was shortest for Microfluidics-FISH and the average volume of sample was smallest. Microfluidics-FISH proved to be reliable and cost-effective rapid testing method of common aneuploidies. Recognizing, ho¬wever, limitations of methods based on FISH it cannot replace conventional karyotyping and be the sole method of diagnosis.

Level of knowledge concerning diet in type 2 diabetic patients and nurses.

Introduction: Among patients with diabetes, there are many myths concerning food products which are believed to lower or not influence the blood glucose (BG) level. The aim of this study was to assess the knowledge of patients with diabetes and hospital nurses concerning popular food products and their impact on BG levels. Materials and methods: The study group consisted of 250 patients with diabetes (DM), members of the Polish Diabetes Association; the other group consisted of 123 healthy nurses (N) from 3 hospitals in Szczecin, Poland. Participants were asked to complete a questionnaire on products common in diabetic diet (grapefruit, honey, coffee substitute, diabetic chocolate, milk soup, pork neck) and their influence on BG levels. Results: The highest percentage of wrong answers was given for pork (DM 71%; N 83%, NS) and grapefruit (DM 51%; N 77%, p < 0.01), while the most correct answers were for honey (DM 69%; N 80%; p < 0.05) and milk soup (DM 64%; N 67%, NS). Negative correlation was found between the number of correct answers and the age of patients (r(s) = −0,14; p < 0.01;) and no correlation between the number of correct answers and the duration of diabetes mellitus (NS). Patients treated with insulin provided correct answers significantly more frequently than patients on oral medication only (44% vs 34.8%; p < 0.01). Conclusions: 1. The level of knowledge concerning products commonly used in diabetic diet among patients with diabetes and hospital nurses is low. 2. Both groups, patients and hospital nurses, need education about diabetic diet.

[Practical implementation of recommendations concerning diagnostic procedures in gestational diabetes]. / Praktyczna realizacja zalecen dotyczacych diagnostyki cukrzycy ciazowej.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with health consequences for both, the mother and her offspring. In Poland, the diagnosis of GDM is based on the recommendations of the Polish Gynecological Society (PTG) and is usually made by obstetricians. OBJECTIVE: The aim of the study was to assess practical implementation of PTG standards of GDM screening and diagnosis. MATERIAL AND METHODS: The study group consisted of 351 pregnant women consulted by a diabetologist: 102 patients between 2008-2010 (PTG guidelines of 2005) and 249 patients between 2011-2013 (PTG guidelines of 2011). Data concerning diagnostic procedures performed by obstetricians--time of diagnostic tests, fasting glucose levels, oral glucose tolerance test (OGTT) results, and GDM risk factors--were collected. Adherence to the diagnostic procedures was assessed. RESULTS: Adherence to the diagnostic guidelines for 2008-2010 was 42.2%. The most common errors were incorrect time of OGGT (36.4%) and wrong interpretation of glycaemia (34.1%). Between 2011-2013 incorrect diagnostic testing was detected in 78.3% of the affected women. The most common deviation was lack of OGTT at the beginning of pregnancy in women with GDM risk factors (91.3%). CONCLUSIONS: A considerable number of GDM women underwent incorrect diagnostic procedures. More precise description of GDM risk factors in PTG recommendations seems to be necessary.

False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.

[Glycated hemoglobin (HbA1c) as a standard diagnostic criterium for diabetes?]. / Czy hemoglobina glikowana (HbA1c) stanie sie standardem w diagnostyce cukrzycy?

Glycated hemoglobin HbA1c is considered the gold standard for assessing the compensation and treatment of diabetes. After the success of the DCCT and UKPDS studies, which showed that HbA1c is an independent indicator of risk for the development of chronic vascular complications of diabetes, this parameter was used for routine monitoring of metabolic control. In 2010, the American Diabetes Association introduced HbA1c determined by HPLC or HPLC-standardized methods for the diagnosis of diabetes as a parameter more accurate and more stable than the determination of fasting plasma glucose or oral glucose tolerance test. HbA1c measurements can be performed by different analytical methods including HPLC, affinity chromatography, electrophoresis and immunoenzymatic and immunoturbidometric methods. Due to differences in the results of HbA1c determined by laboratories using various methods, it is extremely important to standardize methods for the results given by the HPLC method compared to the methods used in the DCCT and UKPDS studies. The problem is even greater as the large discrepancies are observed between the frequency of carbohydrate disorders diagnosed on the basis of determination of HbA1c and glucose, which raise important questions concerning the widespread introduction of HbA1c for the diagnosis of diabetes.

[Aspects of the standardization of glycated hemoglobin (HbA1c) measurement]. / Aspekty standaryzacji oznaczania hemoglobiny glikowanej (HbA1c).

Glycated hemoglobin (HbA1c) is considered the gold standard for monitoring and the treatment of diabetes. After the success of the DCCT and UKPDS studies, which showed that HbA1c is an independent indicator for risk of developing chronic complications of diabetes, intensive work began on the standardization of this parameter. Currently, the process of standardization of HbA1c determination is being pursued by two independent international organizations: NGSP and IFCC. At present most HbA1c determinations carried out worldwide are done via a test which is performed using uniform and standardized methods, which have been certified by the NGSP. At the same time, the IFCC has created a new, more consistent and specific method of standardization, but this method is not used routinely. According to the IFCC standard, HbA1c values are significantly lower compared to the results obtained by NGSP. Moreover, the IFCC has introduced a new alternative unit of HbA1c mmol/mol. Discrepancies between the programs of the two organizations, their advantages and disadvantages, have led to the consensus on global standardization of HbA1c determinations. This paper presents aspects of the standardization of HbA1c determination methods, which takes into account the obtained values and recommended range of values for each group of diabetic patients, as well as the statement of the largest diabetological organization.