Meeting abstracts from the Annual Conference “Clinical Genetics of Cancer 2022”

based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40-50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate can- cer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to high-risk proportions and age of onset.

From time to time young adult patients will present with a desmoid tumour, which arouses suspicion of Familial Adenomatous Polyposis (FAP) and the risk of colorectal cancer. Desmoid tumours are unequivocally associated with FAP and many studies have revealed that there is a generalised genotype/phenotype correlation with the likelihood of a FAP patient presenting with such a tumour. In addition, the entity familial infiltrating fibromatosis is considered allelic to FAP since pathogenic variants in APC have been identified that are associated with this disorder. Thus patients presenting with desmoid disease should be screened for pathogenic variants in APC to either exclude FAP or include it. The majority of patients, however, do not carry a germline pathogenic variant, but rather a somatic mutation in CTNNB1 (β-catenin). Currently, there are only four mutations in CTNNB1 that have been associated with sporadic desmoid disease, c.121A>G; c.122C>T; c.133T>C and c.134C>T; with the majority of mutations occurring at position c.121A>G. The current literature to date suggests that "sporadic" desmoid tumour patients are a result of mutations within CTNNB1 and that inherited pathogenic variants in this gene are not compatible with foetal development. At present, the dogma indicates that only CTNNB1 is associated with sporadic desmoid disease and that APC is uniquely associated with inherited forms of disease. Notwithstanding, there remain a percentage to sporadic desmoid tumour patients who do not have a genetic diagnosis. Given that there are FAP families that do not display an overt FAP phenotype but to present with multiple cases of desmoid disease, we reasoned that some of the sporadic desmoid tumour patients who did present with a CTNNB1 mutation may be the result of an APC mutation located within a region of APC correlated with desmoid tumour development.
based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40-50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate cancer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to highrisk proportions and age of onset. About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. To identify novel high-to-moderate-penetrance germline variants underlying CRC susceptibility, we performed whole exome (WES) and whole genome sequencing (WGS) in Polish CRC families showing a Mendelian inheritance pattern. After WES or GWS, we used our in-house developed Familial Cancer Variant Prioritization Pipeline to identify novel cancer predisposition variants. We identified both nonsense, missense and 5'UTR variants involved in the regulation of innate immune response (SLC15A4), apoptosis and AKT pathway (PTK7), reactive oxygen species and mucus biology (CYBA, TRPM4), Wnt signaling (APCDD1) and histone modification (HDAC5) and in a protooncogene (SRC). Some of the identified variants may show they effect according to a synergistic or polygenic model. Our findings contribute to the identification of unrecognized genetic causes of familial CRC. This is a multicenter, multinational, randomized, 2-arm, double-blind, phase II clinical study with 2000mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 260 tumor free carriers of a known genetic mutation in a major MMR gene (including patients in which the polyps are endoscopically removed) will be randomized 1:1 to receive 2000mg mesalamine or placebo. Patients will be identified through local or national registries and through collaboration with sites. Tumor free patients, assessed by white light high resolution colonoscopy, will be randomized to the study. Blood and stool samples will be collected for analysis of microbiota, ctDNA and potential biomarkers. Biopsies of the normal tissue of ascending colon and rectum will be taken at the first and the last colonoscopy.
The aim of the study is to investigate the effect of regular treatment with mesalamine (5-ASA) on the occurrence of any colorectal neoplasia, tumor multiplicity (the number of detected adenomas/carcinomas) and tumor progression in LS patients. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated. The patients survival in case of early detection of the cancer by FOBT screening and colonoscopy is an indicator of incidence and mortality from CRC. However mortality rates are high in countries with relatively low incidence such as in Moldova, Russia, Montenegro, Poland and Lithuania. For intense in Lithuania the CRC age-standardized incidence rate is 23.4 and mortality rates 13.7 while in the Netherland comparative rates are 40.2 and 13.4 respectively. The first time during 2000 year in Lithuania was introduced in medicine practice guaiac Haemoccult test for early diagnosis of CRC improving and to investigate the possible development of CRC and diagnoses in patients after once testing. Deadline of follow-up for possible development cancer and diagnosis in 374 patients [256 (68%) female and 118 male (32%)] were once tested by Haemoccult was 2008 September (median 8, 7 years). The risk of cancer development and diagnosis was calculated by standard incidence ratio (SIR) use statistic program PY2. In the 243 (66.9%) patents including with positive CRC family history 48(18.8%) female and 22 (18.6%) male, who were tested and did not obtained positive test, SIR for CRC was 1, 09; in the 120 (33.1%) patients, who have obtained positive test, SIR was 2.04 for CRC and 3.07 for all cancer. Any one a CRC did not diagnosed in stage-I (TNM). The results of this study suggest that early CRC detection by once testing Haemoccult is impossible. In 2009 Lithuania started a national Program for CRC screening by fecal immunochemical testing (FIT) and colonoscopy. The screening program was implemented in June 2009 using the FIT (OC-Sensor test, Eiken,Tokyo Japan) with automated reading techniques in one of the biggest Vilnius city Centro Polyclinic. The target population according to criteria in age 50-74 years for potential screening was 45 330 subjects: female 27 909(61.6%) and 17 421(38.4%) male. Patients whose samples revealed an FIT value Hb>100 -ng/ml of buffer underwent colonoscopy. The rate participation we calculated every 2 years because the patents after initial testing with negative FIT test necessary performed regular every 2 year repeating test. Overall 35 689 -13 904(39%) male and 21 785 (61%) female subject from a potential target population were accepted for screening. The participation rate for least once screening over the 7 years (every 2 years) was 78.7%. The participation rate in screening calculated every 2 years 1-4 round was 33.6%, 35.1%, 402%, 23.7% respectively for female and male. Estimated that from 35 689 participated in screening patients in 176(0.98%) was diagnosed CRC cases and from 9 641 non-participated patients was diagnosed 94(0.98%) CRC cases. After calculation of comparative efficacy for diagnosis of CRC by stage I-IV and ten years survival of screened and non-screened patients were not significantly different P=0.128908 and P=0.3898 respectively. Screening of average risk population is limited because the criteria of age are 50-74 years and potential young (below 50 years) subjects with high risk to hereditary cancer including Lynch Syndrome are not accepted in screening. In Lithuania in same period with population screening in 2009 was introduced in medical practice a screen first colon cancer tumour by MSI and IHC staining according to histological criteria and young age below 50 years. We study to estimate the efficacy of cancer diagnoses in young patients below 50 years who had tumour failed to express MLH1, MSH2 and MSH6 use staining MSI and IHC. For period 2009-2019 were diagnosed 54 suspected for Lynch syndrome patients (32 man and 22 women). Any one a CRC did not diagnosed in stage-I (TNM). The distribution of diagnosed CRC stage in each stage were: Stage I-0, II-19(35.2%) III-21(38.8%), IV-10(18.5%), unknown-4(7.5%). Early CRC detection by once testing is impossible. The participation rate for at least once screening over the 7 years of the study was 78.7% with participation rate in each round (1-4) was less than EU guideline set minimum 45% and did not improve a detection of CRC by stage P=0.13 and ten years survival of screened and non-screened of CRC patients is not significantly different P=0.39. Farther research is needed to help to determinate and stratify various risks, such as LS for the development of CRC in low incidence population. Lynch syndrome (LS) is a common hereditary cancer predisposition syndrome. It is caused by mutation in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2 or deletion of last exons in EPCAM gene. Mutation carriers are at high risk of developing colorectal cancer (CRC) and endometrial cancer (EC). They have also increased risk of some extra-colonic cancers such as ovarian, small bowel, urinary, biliary tract, gastric, and brain tumors. Ovarian cancer (OC) is third most commmon cancer in Polish LS women constitutes about 5% of all LS cancer. There is no consensus guidelines for OC prevention in LS women. The aim of this study was to evaluate and compare ovarian cancer risk in our series of 289 families with identified pathogenic mutations (referred as Lynch syndrome families) to the general population. We observed increased risk of OC in Polish LS families in copmarision to the general polulation. Moreover, high risk of ovarian cancer was found for LS women under 50 years of age. Furthermore 6 out of 17 (35%) early-onset patients from LS families died from ovarian cancer within 2 years of diagnosis. Due to the increased risk of ovarian cancer in LS women and low efficiency of the gynecological screening, for female carriers of a pathogenic variant in MLH1 and MSH2 genes prophylactic adnexectomy should be recommended after 35year of age. Additionally because of the small number of cases of pathogenic mutations in the MSH6, PMS2 and EPCAM gene, the validity of prophylactic adnexectomy cannot be demonstrated. Recently, PARP inhibitors have been introduced as a promising treatment option for pancreatic cancer patients with mutations in the BRCA1/2 genes.

Aim
The purpose of this study is to review the spectrum of detected mutations in BRCA1/2 genes in patients referred for molecular diagnosis due to consideration of PARPi treatment.

Material and Methods
Between 2020 and 2022, 143 patients with stage III and IV pancreatic cancer were tested for BRCA1/2 genes by NGS in DNA isolated from 116 (82%) blood samples and 28 (18%) cancer tissue samples.

Results
In 3/28 (11%) tissue samples showed DNA degradation and no test result was obtained. No mutations in BRCA1/2 were detected in any of the tissue samples tested. All 8 pathogenic mutations were detected in blood samples. Two mutations were detected in the BRCA1 gene and six in BRCA2. In total, mutations were detected in 5.7% (8/140) of the patients studied. Conclusions BRCA1/2 diagnosis for pancreatic cancer should be carried out by NGS because the mutations are mostly confined to the BRCA2 gene and additionally scattered throughout the gene. In one case, founder mutations were detected in the BRCA1 gene. Breast cancer is the most common cancer in women and in majority it is thought to be sporadic. 10-15% of breast cancer cases is considered to be hereditary. The most common genetic susceptibility is caused by mutation in BRCA1 and BRACA2 gene mutations which are responsible for 5-10 % of all familial cases. Cybulski et al. and Erkko et al. described the mutation in PALB2 and RECQL genes mutations increasing risk of breast cancer. In Europe the recurrent mutation of this gene are c.1667_1667+3delAGTA in the RECQL gene and c.509_510delGA and c.172_175delTTGT in the PALB2 gene. In our region also frequent is deletion of exon 9 of the PALB2. We developed the method for fast and easy identification of those 4 mutation. The method is based on C-HRM technique developed by our team few years ago which let to detect the point mutations and copy number variations in the same time. The Patent Office of the Republic of Poland granted the patent (official number P.436028) to the Institute of Human Genetics PAS for the invention entitled: "Method and diagnostic kit for detecting RECQL and PALB2 gene variants in Polish patients with breast cancer". Authors of the invention are: Andrzej Pławski, Jan Lubiński, Cezary Cybulski, Zdenek Kleibl, Emilia Lis-Tanaś, Paweł Boruń. a post-transcriptional increase in gene expression. The final effect of miRNA's influence on mRNA and the resulting increase in expression seems to be dependent on specific cell conditions, mRNA sequence and other cofactors. There are numerous mechanisms responsible for the miRNA-dependent reduction of gene expression, which include both translation initiation as well as post-initiation mechanisms. In both types of interactions, miRNPs play a key role in reducing gene expression. The literature suggests that there are several microRNAs (miRNAs, miRs) that exhibit either increase or decrease of expression in liquid-biopsy samples during early onset of several malignancies including breast and ovarian cancer. It is important to mention that scientific literature suggests ethnic-related changes in the expression of microRNA molecules, which requires tailoring of the assays to local requirements. By selecting proper miR molecules, it is possible to develop highly specific and sensitive test for cancer detection, prognosis or even selecting tailored therapy. In this presentation we are demonstrating preliminary results covering four patients assessed in two different timepoints over the span of monitoring and therapy period as a part of National Prevention Programme of BRACA1/BRACA2 positive patients. Testing was performed on freshly collected serum samples that undergo microRNA extraction process and expression assessment utilising gold standard for miR detection -Real-Time RT-PCR with TaqMan ® Array Card: TaqMan ™ Advanced miRNA Human Serum/ Plasma Cards able to detect 188 distinctive microRNAs. Obtained results are promising, exhibiting the ability to differentiate expression profiles for two different timepoints when compared to healthy individuals. This might enable differentiation between early onset of disease and progression in the future. In order to fully evaluate the preliminary results, in the next step we plan to evaluate additional samples of BRCA1/BRCA2 positive patients both not exhibiting symptoms of malignancies as well as on different stages of active cancer therapy out of over 140 currently banked with array screening together with additional healthy patients which will allow exclusion of both individual and environmental factors.

Introduction
PTEN hamartoma tumor syndrome (PTEN-HTS or PHTS, OMIM 158350, ORPHA:306498) is the collective term for a group of syndromes, including Cowden syndrome, adult Lhermitte-Duclos disease, Bannayan-Riley-Ruvalcaba syndrome, and Proteus -like syndrome, caused by germline mutations in the PTEN gene, located on 10q23.3. Inheritance of PHTS is autosomal dominant. The syndrome is rare, with an incidence of 1 in 200000, however it is very likely to be underestimated. Hamartomas are a common manifestation of the PHTS. The lifetime risk (LTR) of developing breast cancer for women is about 77-85%, for endometrial cancer 19 -28%. LTR for thyroid cancer for the carriers is approximately 21-38%, for renal cell cancer 15-34%, for colorectal cancer 9%-16%, for melanoma up to 6%. Affected individuals usually have macrocephaly and frequently present with rare benign mucocutaneous lesions. Diagnostic criteria for PHTS are regularly updated by the National Comprehensive Cancer Network.

Material and methods
In our Institution NGS sequencing has been made available for clinical use since 2018 year. Our multigene panel includes PTEN gene. During the last 4 years at our Genetic Counselling Unit we identified 6 unrelated patients with symptoms prompting PHTS diagnosis. The probability of finding PTEN mutation was calculated for each individual using The Cleveland Clinic Adult Clinical Scoring System. All the patients were evaluated by the same clinical geneticist before and after the test. Written informed consent for the genetic testing had been obtained by the same medical doctor. After establishing diagnosis all the patients received detailed genetic counsel and were included into surveillance programme, according to the guidelines (ERN-Genturis/ NCCN -combined). DNA was extracted from the peripheral blood leukocytes using QIASymphony QIAGEN technique. For the first group we used Illumina Platform NextSeq500, for the last 3 patients we used Ion AmpliSeq On-Demand DNA Panel by Thermo Fisher. The pathogenicity of the variants/ mutations was assessed according to the Recommendations from the ClinGen PTEN Expert Panel and checked in ClinVar database. Results PTEN -HTS (PHTS) diagnosis has been confirmed in 6 patients (4 women, 2 men) carrying 6 different germline pathogenic PTEN mutations: one in the 1 st exon, one in exon 3/9, two different in exon 5/9, one in exon 6/9, one in intron 7, one also intronic -after exon 8. All the patients had OFC ≥ 60 cm. Both men presented with benign only tumours -mainly skin lesions and gastrointestinal polyps and both of them had established diagnosis of autism spectrum disorder. Two of 4 women presented with multiple cancer ( breast, endometrial, ovarian in one and breast and rectal cancer in the second one). Unexpected diagnoses in our group of patients were: thyroid cancer at the age of 5 years, schwannoma and neurofibroma.

Conclusions
This is the first Polish study of the genotype -phenotype correlations among patients with PHTS. We were not able to prove any founder/ recurrent mutations in this group. We found 6 different pathogenic mutations in our unrelated 6 patients. Our study confirms value of the established clinical criteria and online tools for identifying PTEN-HTS/Cowden syndrome in Polish patients. The routine measuring of head circumference in hereditary cancer clinics seems to be a good recommendation. In general terms epigenetic mechanisms of gene expression regulation alter gene expression without changing primary gene sequence. There is a number of epigenetic mechanisms that orchestrate gene expression and render cell phenotype. Malfunctioning of those mechanisms leads to disease such as neoplastic transformation. In principle each of those mechanisms can be targeted by treatment or a become source of biomarkers. However, currently only assays targeting DNA methylation changes are finding significantly increasing use in clinical disease management. DNA methylation is a covalent addition of the methyl groups to cytosines within CpG dinucleotide and methylation of the promoter sequences interferes with gene transcription. There is already substantial evidence that biomarker assays targeting disease related methylation changes can effectively be utilized as biomarkers at all stages of the clinical disease management: from risk assessment through early diagnosis and treatment personalization to post treatment surveillance. Specifically, one of the largest clinical trials have recently shown that methylation biomarker-based cancer detection in liquid biopsy allows to detect cancer in patients with remarkable specificity and sensitivity. Moreover, detectable in blood methylation of BRCA1 gene has been proposed as biomarker of predisposition to breast and ovarian cancers. The methylation of MGMT gene has long been used to guide treatment of glioblastoma multiforme patients. And recently, the genome wide profiling methylation has been suggested as alternative to standard histopathology method for the classification of brain tumours by the World Health Organization. With those developments methylation biomarkers can significantly contribute and change cancer management as well as play a significant part in personalized medicine. In my talk I will review current applications of the methylation biomarkers in clinical disease management.

Introduction
According to the International Agency for Research on Cancer (IARC) 19 million new cases of cancer are diagnosed every year worldwide. In Poland above 171 000 new cases of cancer are diagnosed each year. Due to a large number of cancers, it is important to try to identify new early detection markers. For many years, elements' effects on human life and health, including the occurrence of cancer, have been widely studied. In this research we want to find whether selected elements (Se, Cu, Cd) levels in serum/blood could be related to the cancer occurrence. Methods For analysis, 10 mL of peripheral blood was collected for elements levels in serum/blood and were determined at the time of diagnosis of cancer, before the start of treatment. Elements levels were quantified by inductively coupled mass spectrometry (ICP-MS). We assigned patients to one of four categories of elements levels based on the distribution of selected element levels in the entire study group. All statistical calculations were performed using: R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria (R version 4.04). The studies was conducted in accordance with the Helsinki Declaration and with the consent of the Ethics Committee of Pomeranian Medical University under the number KB-0012/73/10. All participants provided written consent to be enrolled in the herein studies. Findings Low selenium level was associated with an odds ratio of 5.81 (95% CI: 2.18 to 16.52; p = 0.0001) for lung cancer, 5.44 (95% CI: 2.14 to 14.62; p < 0.001) for laryngeal cancer and 13.78 (95% CI 6.31 to 29.82; p < 0.001) for colorectal cancer. Moreover, odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98 to 32.3; p < 0.001). In research on blood cadmium level as a marker for early lung cancer detection -odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold higher (OR = 4.41, 95% CI: 2.01 to 9.67; p < 0.01). The association was present in former smokers (OR = 16.8, 95% CI: 3.96 to 71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34 to 4.38) or in never smokers (OR not defined).

Conclusion
Low selenium level (<60 μg/l; serum) may be a marker for early detection of the lung, larynx and colorectal cancers. High copper level (>930 μg/l; blood) may be a marker for early detection of colorectal cancer. High level of cadmium (>0.47 μg/l; blood) may be a marker for early detection of lung cancer, especially in former smokers. It seems that determining the level of Se, Cd and Cu could be a marker for selection for control examinations in surveillance as a valuable complement to existing diagnostic procedures.
Since the data from prospective studies are available, one of the critical challenges in oncology is to reverse carcinogenic effect of elements. One of major concerns in Polish women population is arsenic. Marciniak et. al. shown that arsenic is one of risk factors for breast cancer for carriers and non-carrier of deleterious variants in BRCA1 gene. Most of arsenic is ingested with food. Therefore the diet became the first trial of blood arsenic lowering study. After 30 months of low arsenic diet, 55% of participants showed blood arsenic decreased by 55%. Selenium has antagonistic effect on arsenic, both in absorption and metabolism. We have conducted an analysis of selenium to arsenic ratio. There is an optimal range of Se/As ratio which is correlated with significantly lower cancer incidence. Some papers suggest also that vitamin C may be beneficial in lowering blood arsenic levels. We have performed a pilot study with orally administered vitamin C supplement. After 30 days of daily intake of 1g of vit C, arsenic level was significantly decreased in 95% participants. In men, blood lead level is associated with 7 times increased risk of cancer. In a pilot study we found a substance that is capable to reduce blood lead level to background level. In conclusion, blood arsenic, selenium and lead are strong cancer risk factors. It seems that we are able to reverse the adverse effect of these element by simple diet modification or vitamin C supplementation. Grant: INNOMED/I/16/NCBR/2014 SELINA is a clinical study on influence of selenium blood levels optimization on cancer occurrence and all cause mortality in females from families with increased risk of hereditary breast cancers. 7456 women at the age of at least 40 years have been recruited from centers in Poland. According to planned protocol, 40 months after recruitment, decoding for safety reason was performed. Compliance rate was 81%. Intervention did not cause undesired effects in any arm. By contrast, in some sub-groups very promissive correlations have been found. The strongest positive effects were noted in subgroups of BRCA1(-) (without occurrence of Polish founder constitutional mutations): Selenium deficiency (blood level <98μg/l) on supplement Sel-BRCA1 ® (ethanol solution of sodium selenite), placebo or diet and selenium excess (blood level >108μg/l) on diet. In all above subgroups combined, all cause mortality was decreased more than 3 times in females who achieved blood Selenium level 98-108 μg/l 5 and 1162 vs 35 and 2509; p=0.0154, OR=3. for obtaining population results for the defined health contribution. Implementation takes place through the spontaneous involvement of interested medics or medical organizations and entities. The material discusses proposals for a smooth and effective transition and improvement of care for the population under care. Solutions have been proposed that allow for higher population propagation, using existing resources by coordinating care and integrating cooperation with primary health care, outpatient care and gynecology, oncological surgery and clinical oncology departments and areas. Efforts should focus on: 1-education of medical, non-medical and managerial and coordination staff in the field of new competences, 2-building care plans and organizing e-consultations 3-intensification of systemic cooperation with the National Health Fund-(NFZ) and E-Health Center-(CEZ), mainly through IT integration using the P1 platform and through the use of integrated office and hospital peripheral systems and systematic modification of the components of the National Health Fund's contracts. 4-using the implementation of care coordination in Primary Care (POZ) and creation of an electronic national cancer registry-(eKRN) to build new effective cooperation in the field of oncological prevention programs, especially in the field of surveying.
Proper implementation of care for high-risk families according new program NFZ in the population may make it possible to achieve an improvement in the results of treatment of the above-mentioned cancers as well as other cancers in Poland in the coming years.

Introduction
Coincidence of breast cancer with thyroid cancer has been demonstrated in literature previously. It has been recognized that breast cancer survivors have almost twofold increased risk of developing thyroid cancer and the risk is higher than the risk of breast cancer in thyroid cancer survivors. Several factors have been indicated to be involved in both thyroid and breast cancer development. Two genes were identified to be connected with coexisting breast and thyroid cancer: CHEK2 and PARP4. To our knowledge, no study has examined the risk of developing metachronous thyroid cancer in breast cancer patients with mutation in CHEK2 or other genes.

The aim of study
The aim of this study is to identify the genes of high risk of thyroid cancer among breast cancer patients.

Patients
We recruited 10 869 breast cancer patients. The available information included the age of breast cancer diagnosis, deaths, year of breast cancer surgery, the treatment oncology center, lymph node status, tumor size, histopathology, estrogen-receptor status, progesterone-receptor status, HER2 status, multicentricity, bilaterality, previous treatment (chemotherapy, radiotherapy, hormonotherapy), adnexectomy, other