Report on the Effect of the Implementation of an Early Detection and Prevention of Cancer Program on Families at High Hereditary Risk-Concentrating on Patients Undergoing Genetic Diagnostics and Counseling in Central Poland.

Over a 46-month period, the objectives of the National Cancer Control Program (NCCP, pol. Narodowy Program Zwalczania Chorób Nowotworowych), coordinated by the Ministry of Health, were pursued by conducting genetic diagnostics on individuals at high risk of developing cancer. A total of 1097 individuals were enrolled in the study, leading to the identification of 128 cases of germline mutations. The implementation of the NCCP led to the identification of genetic mutations in 4.43% of the patients qualified for BRCA1 and BRCA2 screening tests, in 18.18% of those qualified for a comprehensive next-generation sequencing (NGS) panel in cases of breast and ovarian cancer, and in 17.36% of cases of colorectal and endometrial cancer. The research conducted allowed us to establish individualized preventive and therapeutic approaches for mutation carriers. However, the results prove that liberalizing the inclusion criteria for high-throughput diagnostics and the use of broad gene panels could significantly increase the percentage of detected carriers. This publication serves as a summary and discussion of the results obtained from the implementation of the NCCP as well as of the role of genetic consulting in personalized medicine.

Age of natural menopause onset in BRCA1/2 carriers - systematic review and meta-analysis.

INTRODUCTION: Germinal pathogenic variants in BRCA1 and BRCA2 genes are associated with high risk of cancers, including breast, ovary, fallopian tubes and primary peritoneal. Non-oncological implications of germline pathogenic variants in BRCA1 and BRCA2 genes, complicating reproductive health are less described. The influence of BRCA1 and BRCA2 on age of natural menopause remains inconclusive and controversial. MATERIAL AND METHODS: PubMed database was searched for potentially relevant abstracts. Studies which were not case-control, cohort or cross-sectional studies were subsequently excluded. Reference lists from systematic reviews or meta-analyses, dealing with the topic of menopause and BRCA1 and BRCA2 germinal pathogenic variants, were also checked to identify eligible studies. We also included our original, unpublished data from families, affected by BRCA1 or BRCA2 pathogenic variant, consisted of at least two postmenopausal female siblings with differing variant status. RESULTS AND CONCLUSIONS: Initial database search retrieved 193 abstracts. We identified 4 eligible studies for meta-analysis. Two studies not reporting dispersion measures and not reporting age of natural menopause in control group were left in summary for illustrational purposes, yet were excluded from meta-analysis. 4 studies and our original, unpublished data, combining data from 1535 germinal BRCA1 and BRCA2 pathogenic variant carriers and 3191 control individuals, did not support the hypothesis of association between germinal pathogenic variants of "breast cancer genes" and premature menopause.

The Usefulness of Cell-Based and Liquid-Based Urine Tests in Clarifying the Diagnosis and Monitoring the Course of Urothelial Carcinoma. Identification of Novel, Potentially Actionable, RB1 and ERBB2 Somatic Mutations.

Bladder cancer is one of the most common cancers in global statistics. One of the issues associated with this disease is the high incidence of cases with delayed diagnosis and what factors correlate with worse treatment outcomes. A possible reason for this may be the rather limited availability of non-invasive diagnostic tools. This short communication presents a case of a 68 year old male patient after an ineffective therapy, carried on for several years with symptoms commonly associated with prostate overgrowth that masked a carcinoma in situ of the urinary bladder. Implementation of several diagnostic techniques, including urine sediment cytology, immunocytochemistry, the fluorescence in situ hybridisation technique, the Bladder EpiCheck test and whole-genome sequencing, enabled the establishment of a correct diagnosis, implementation of appropriate treatment and provision of patient-friendly monitoring. The described case emphasises the usefulness of cell-based and liquid-based urine tests in bladder cancer diagnostic procedures.