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Author(s): C. Cybulski[sup.1] , W. Kluźniak[sup.1] , T. Huzarski[sup.1] , D. WokoÅorczyk[sup.1] , A. Kashyap[sup.1] , A. Jakubowska[sup.1] , M. Szwiec[sup.2] , T. Byrski[sup.1] , T. DÄbniak[sup.1] , B. Górski[sup.1] [...]

Immune checkpoint inhibitors have improved the treatment of metastatic renal cell carcinoma (RCC), with the combination of nivolumab (NIVO) and ipilimumab (IPI) showing promising results. However, not all patients benefit from these therapies, emphasizing the need for reliable, easily assessable biomarkers. This multicenter study involved 116 advanced RCC patients treated with NIVO + IPI across nine oncology centers in Poland. Blood markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), eosinophils, and monocytes were assessed at baseline, after three months, and before disease progression (PD). The prognostic significance of these parameters was analyzed using linear regression, Kaplan-Meier survival analysis, and Cox regression models. After a median follow-up of 11.8 months, the progression-free survival (PFS) was 12.8 months (95% confidence interval [CI] 5.7-28.1), while the overall survival (OS) was 27.3 months (95% CI 16-not reached). Patients with an NLR increase of ≥ 25% had a PFS of 8.2 (3.1-24.7) months compared to 17.5 (8.6-28.1) months in those with a rise in < 25% (p = 0.015). Similarly, a ≥ 25% increase in PLR was linked to a PFS of 6.8 (2.8-8.3) months compared to 17.4 (8.4-28.1) months (p < 0.001). Multivariate analysis confirmed PLR as an independent predictor of PFS (HR 2.9, 95% CI 1.5-5.6, p = 0.001), while elevated eosinophil levels were associated with a reduced risk of death (HR 0.2, 95% CI 0.04-0.9, p = 0.05). No other analysis was statistically significant. NLR, PLR, and eosinophil levels may serve as valuable biomarkers for predicting treatment response in RCC patients receiving NIVO + IPI., Competing Interests: Declarations. Competing interests: RPM has received travel grants from Accord, BMS, MSD, and lecture fees from Astra Zeneca, BMS, GSK, Novartis, Roche, MSD; AD has received travel grants and lecture fees from Roche, BMS, Janssen, Molteni, MSD, Accord; AGW has received travel grants and lecture fees from Roche, Novaris, Lili, Astellas, Pfizer, Amgen, Swixx, Pierre Fabre, Egis, BMS, MSD; JC has received lecture fees from BMS; NVV has no financial interests; DTM has received travel grants and lecture fees from MSD, Pierre Fabre, BMS, Novartis, Pfizer; JD has received travel grants and lecture fees from Amgen, AstraZeneca, BMS, MSD, Novartis, Nutricia; AR has received travel grants and lecture fees from Roche, BMS, Ipsen, Pfizer, Novartis, Gilead, MSD; AB has received travel grants and lecture fees from BMS, MSD, Astellas, Merck, Servier, Astra Zeneca, Pfizer; MS has received travel grants and lecture fees from Roche, BMS, Janssen, MSD, Amgen, Astellas., Ipsen, Pfizer, Novartis, Gilead; AGU has received travel grants from GSK, Lilly, Astra Zeneca, Gilead, Accord, and lecture fees from Astra Zeneca. JW has no financial interests; PB has received travel grants, lecture fees, and advisory boards from AstraZeneca, MSD, GSK, Pharma; ŁS has received travel grants from BMS, Accord; MP has received travel grants and lecture fees from AstraZeneca, Roche, Novartis, Elli Lilly, Janssen, Gilead, and Amgen. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Jagiellonian University Medical College (approval number 118.0043.1.115.2024, dated April 19, 2024). Consent to participate: Informed, institutional consent was obtained from all individual participants included in the study before starting treatment., (© 2025. The Author(s).)

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., (© 2024. The Author(s).)

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.

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.

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.

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.

Background: Cancer influences various aspects of patients' functioning. Cancer patients face not only medical problems but also organizational, socio-psychological, and spiritual problems. Their needs often seem to be unrecognized because patients do not express their concerns and clinicians do not ask appropriate questions. Unmet needs impact patients' quality of life. The aim of this study was to select, adapt, validate, and introduce a simple instrument for estimating cancer patients' unmet needs in Poland., Methods: The Needs Evaluation Questionnaire (NEQ) was chosen for validation in a Polish population. The Polish version of the NEQ was developed with a back-translation procedure, as approved by a psycho-oncologist and a public health specialist. The psychometric properties of the NEQ (content analysis, reliability, construct validity, comprehensibility, and acceptability) were measured., Results: This study was performed on a group of 121 cancer patients. The median time of completion for the NEQ was 10 min. The form, length, and font size of the NEQ were accepted by the respondents. Overall, the meaning of the questions was well understood, with only a few cases of discreetly heterogeneous interpretation of the content. The questionnaire showed good reliability and internal factor structure validity., Conclusion: The NEQ is a simple, easy-to-administer instrument with good psychometric properties and seems to be useful in assessing the unexpressed needs of cancer patients.

There is emerging interest in the relationship between several serum micronutrients and the prognosis of patients with breast cancer. The relationship between serum zinc and copper levels and breast cancer prognosis is unclear. In our study, we included 583 patients with breast cancer diagnosed between 2008 and 2015 in the region of Szczecin, Poland. In a blood sample obtained before treatment, serum zinc and copper levels were quantified by mass spectroscopy. Each patient was assigned to one of four categories (quartiles) based on the distribution of the elements in the entire cohort. Patients were followed from diagnosis to death over a mean of 10.0 years. The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio ( p < 0.001). The multivariate hazard ratio (HR) for breast cancer death was 2.07 (95% CI 1.17-3.63; p = 0.01) for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific survival after breast cancer diagnosis.

Purpose: Cancer itself and its treatment have a multifaceted impact on patients' daily lives. The aim of the study was to determine unmet non-medical needs among Polish cancer patients., Methods: Survey research using a 23-item Needs Evaluation Questionnaire (NEQ) was carried out among 1062 cancer patients from different regions of Poland. Quantitative and qualitative analyses were performed., Results: The quantitative analysis showed that 48% of the NEQ items (11/23) were expressed as unmet needs by at least half of patients. Unmet information needs were indicated by patients most often: information about their diagnosis, exams, treatment, future condition, funding and economic support. Cancer patients would like to get more attention from medical staff. Unmet needs were most frequently expressed by respondents who were men, with a lower level of education, living in village, pensioners. Qualitative analysis showed that each need may be understood in a variety of different ways across the cohort. Some patients added comments that the completing NEQ helped them to notice their non-medical needs., Conclusion: Polish cancer patients have some unmet non-medical needs, especially informative needs., (© 2024. The Author(s).)

Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% ( p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.

The APOBEC3B gene belongs to a cluster of DNA-editing enzymes on chromosome 22 and encodes an activation-induced cytidine deaminase. A large deletion of APOBEC3B was associated with increased breast cancer risk, but the evidence is inconclusive. To investigate whether or not APOBEC3B 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 APOBEC3B 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, p = 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, p = 0.74). Clinical characteristics of breast tumors in carriers of the APOBEC3B 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 APOBEC3B deleterious mutation p.Val262Phefs does not confer breast cancer risk. These data do not support the hypothesis that APOBEC3B is a breast cancer susceptibility gene.

Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM&#95;130384.3: c.1152&#95;1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152&#95;1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer., Competing Interests: Declaration of interests M.R.A. has equity ownership in Genewsie Inc., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer is the most common cause of cancer death worldwide. It is the most frequently diagnosed cancer in men. Lung cancer causes not only physical symptoms related to the disease itself and its treatment but also numerous mental, social and spiritual problems. The aim of the study was to assess non-medical needs among male lung cancer patients during oncological treatment., Materials and Methods: The study was conducted on a group of 160 men (mean age 67 years) treated for lung cancer from June 2022 until November 2022 in 5 oncological centers in Poland. The Needs Evaluation Questionnaire (NEQ) was used. The NEQ explores five areas of patients' needs: informative, connected with assistance/care, relational, material and psycho-emotional support., Results: All participants (except one) expressed some unmet non-medical needs (mean and median 11). Male lung cancer patients indicated informative needs most frequently. There were no significant differences between expressed unmet needs based on age, place of residence, professional activity or marital status., Conclusions: The NEQ seems to be a proper instrument to explore the non-medical needs of cancer patients. Adequate measures to address the unmet needs of lung cancer patients could contribute to an improved quality of life.

Background: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation., Methods: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast cancer or for benign conditions. Dates of death were obtained from the Polish Vital Statistics Registry. Causes of death were determined by medical record review. Predictors of survival were determined using the Cox proportional hazards model., Results: In all, 839 patients with a CHEK2 mutation were matched to 839 patients without a mutation. The mean follow-up was 12.0 years. The 15-year survival for CHEK2 carriers was 76.6% and the 15-year survival for non-carrier control patients was 78.8% (adjusted HR = 1.06; 95% CI: 0.84-1.34; P = 0.61). Among CHEK2 carriers, the 15-year survival for women who had an oophorectomy was 86.3% and for women who did not have an oophorectomy was 72.1% (adjusted HR = 0.59; 95% CI: 0.38-0.90; P = 0.02). Among controls, the 15-year survival for patients who had an oophorectomy was 84.5% and for women who did not have an oophorectomy was 77.6% (adjusted HR = 1.03; 95% CI: 0.66-1.61; P = 0.90)., Conclusion: Among women with breast cancer and a CHEK2 mutation, oophorectomy is associated with a reduced risk of death from breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs., Methods: The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated., Results: The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01)., Conclusions: Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required., (© 2022. The Author(s).)

Background and Objectives : In Poland, the rates of morbidity and mortality due to cervical cancer are amongst the highest in Europe. A significant percentage of newly diagnosed cases of cervical cancer are at an advanced stage. Unfortunately, only about 20% of Polish women take part in cervical cancer screening. The aim of the study was to assess students' knowledge of cervical cancer risk factors and prevention. Materials and Methods : The study was provided to Polish students from various universities and faculties between May 2020 and November 2020. The questionnaire was designed specifically for this study and was validated. The chi-square test was used to compare the responses between subgroups. Results : The study was carried out on a group of 995 students (80.6% women, 19% men, 0.4% no data), (average age 21.9 years). Most students knew that the main risk factor for cervical cancer is human papillomavirus (HPV) infection (82% of all responders; 86% of medical students; 73% of non-medical students; p < 0.001). Only 40% of students knew that in Poland the Population Prevention and Early Diagnosis Program is carried out on women aged 25-59 years every three years. Most students correctly indicated that cervical cancer screening in Poland is performed using cervical cytology and were familiar with the basis of cytology. Only 57% of students knew that there are no specific early symptoms of cervical cancer. A total of 78% of all respondents knew that HPV vaccination reduces the risk of cervical cancer. Medical students and students who are sexually active demonstrated a better knowledge of cervical cancer. Conclusions : The Polish students had some knowledge of cervical cancer risk factors and primary and secondary prevention. Significantly better knowledge was demonstrated by medical students. Some efforts should be made to ensure that young people, who are not associated with medicine are better educated about cervical cancer in order to reduce the overall incidence and improve early detection rates.