At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 ...IgG antibodies against the S1 subunit of the virus’s spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1–5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2–3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.
To optimize genetic testing, it is necessary to establish the spectrum of breast cancer‐predisposing mutations in particular ethnic groups. We studied 1,018 women with a strong family history for ...breast cancer (families with hereditary breast cancer; HBC) from genetically homogenous population of Poland, which is populated by ethnic Slavs, for mutations in 14 cancer susceptibility genes. Additionally, we compared the frequency of candidate pathogenic variants in breast cancer cases and controls. Germline mutations were detected in 512 of 1,018 probands with breast cancer (50.3%), including BRCA1/2 mutations detected in 420 families and non‐BRCA mutations seen in 92 families. Thirteen BRCA1/2 founder mutations represented 84% of all BRCA1/2‐positive cases. Seven founder mutations of CHEK2, PALB2, NBN and RECQL represented 73% of all non‐BRCA‐positive cases. Odds ratios for hereditary breast cancer were 87.6 for BRCA1, 15.4 for PALB2, 7.2 for CHEK2, 2.8 for NBN and 15.8 for RECQL. Odds ratios for XRCC2, BLM and BARD1 were below 1.3. In summary, we found that 20 founder mutations in six genes (BRCA1/2, CHEK2, PALB2, NBN and RECQL) are responsible for 82% of Polish hereditary breast cancer families. A simple test for these 20 mutations will facilitate genetic testing for breast cancer susceptibility in Poland. It may also facilitate genetic testing for breast cancer susceptibility in other Slavic populations and women of Slavic descent worldwide.
What's new?
Poland is a genetically homogeneous population similar to Iceland, currently designing national policies for genetic testing. To define the range of pathogenic mutations, the authors conducted a large analysis of breast cancer susceptibility genes, defining pathogenic mutations in 50.3% families with hereditary breast cancer. They identified 20 distinct founder mutations in six genes that were responsible for more than 80% of all detected mutations; these 20 mutations could be combined in a single genetic test of breast cancer susceptibility in Polish women.
Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and ...progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.
This study aimed to evaluate the long-term effectiveness of COVID-19 vaccination in healthcare workers by analyzing the population's response to the vaccine after two years, based on anti-SARS-CoV-2 ...protein S antibody levels. Additionally, the study aimed to assess the impact of basic factors on antibody levels.
A total of 4,090 healthcare workers were included in the study, and their antibody levels were measured using ELISA to detect anti-SARS-CoV-2 immunoglobulin G (IgG). Statistical analysis was conducted to examine the influence of COVID-19 infection, vaccination status, and number of vaccine doses on antibody concentrations.
The majority of participants (85.1%) received the Pfizer/BioNTech vaccine, while a smaller percentage chose vector vaccines such as AstraZeneca and Johnson & Johnson. The incidence of COVID-19 among vaccinated individuals was relatively low for all vaccines, confirming their effectiveness in preventing symptomatic SARS-CoV-2 infection. The study observed variations in IgG antibody levels within the study population, with only 0.46% of individuals testing negative for the presence of antibodies. The average anti-SARS-CoV-2 IgG values showed significant differences across consecutive 3-month periods following infection or vaccination, with a gradual decrease over time. Notably, the most significant changes in antibody levels were observed within the first 6 months (mean values ranged from 3647.11 BAU/ml to 2601.49 BAU/ml). Subsequently, minor fluctuations were observed, with mean antibody values hovering around 2000 BAU/ml. The differences between average anti-SARS-CoV-2 IgG values between consecutive 3-month periods from disease onset were statistically significant.
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;
= 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01;
= 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.
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.
The presented research made it possible to obtain the characteristics of changes in anti-SARS-CoV-2 IgG within one year of vaccination in healthcare workers.
The research group consisted of 18,610 ...participants represented by medical and administration staff. IgG antibody concentrations were determined by ELISA.
At 5-8 months after full vaccination, the levels of anti-SARS-CoV-2 IgG with equal vaccines were similar. The exception was JNJ-78436735, for which IgG levels were significantly lower. In the 9th month after vaccination, an increase in the anti-SARS-CoV-2 IgG level, suggesting asymptomatic infection, was observed in a large group of participants. Significantly higher levels of anti-SARS-CoV-2 IgG antibodies were observed after the booster dose compared to the second dose. The increase in antibodies was observed already around the 5th day after the injection of the booster dose, and was maximized at approximately the 14th day.
The cut-off date for protection against the disease seems to be the period 8-9 months from the vaccination for mRNA vaccines and 5-6 months for vector vaccines. The introduction of a booster dose was the right decision, which could have a real impact on restricting the further transmission of the virus.
The
gene belongs to a cluster of DNA-editing enzymes on chromosome 22 and encodes an activation-induced cytidine deaminase. A large deletion of
was associated with increased breast cancer risk, but ...the evidence is inconclusive. To investigate whether or not
is a breast cancer susceptibility gene, we sequenced this gene in 617 Polish patients with hereditary breast cancer. We detected a single recurrent truncating mutation (c.783delG, p.Val262Phefs) in four of the 617 (0.65%) hereditary cases by sequencing. We then genotyped an additional 12,484 women with unselected breast cancer and 3740 cancer-free women for the c.783delG mutation. The
c.783delG allele was detected in 60 (0.48%) unselected cases and 19 (0.51%) controls (OR = 0.95, 95% CI 0.56-1.59,
= 0.94). The allele was present in 8 of 1968 (0.41%) familial breast cancer patients from unselected cases (OR = 0.80, 95% CI 0.35-1.83,
= 0.74). Clinical characteristics of breast tumors in carriers of the
mutation and non-carriers were similar. No cancer type was more frequent in the relatives of mutation carriers than in those of non-carriers. We conclude the
deleterious mutation p.Val262Phefs does not confer breast cancer risk. These data do not support the hypothesis that
is a breast cancer susceptibility gene.
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;
= 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.
Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a ...BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C>T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6–1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene.
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