Meeting abstracts from the Annual Conference Clinical Genetics of Cancer 2018

A1 Search for new genomic changes associated with high risk of cancer Cybulski C, Kluźniak W, Huzarski T, Wokołorczyk D, Rusak B, Stempa K, Kashyap A, Jakubowska A, Szwiec M, Dębniak T, Gronwald J, Narod SA, Akbari MR, Lubiński J, the Polish Hereditary Breast Cancer Consortium Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland; Clinics of Oncology, University Hospital in Zielona Góra, Zielona Góra, Poland; Women’s College Research Institute, Toronto, ON, Canada Hereditary Cancer in Clinical Practice 2019, 17(Suppl 1):A1

The field of familial cancer genetics is continuously on the move. In this presentation I will highlight three topics that are of growing interest. The first topic is the use of gene panels as a means not to only test for the genes that are related to the cancer that triggered referral, i.e. diagnostic testing, but also to screen all other genes on that panel for possible mutations. A recent development in the Netherlands is to perform whole genome sequencing of both tumour and lymphocytes in cancer patients; the latter with the goal to help selecting the somatic variants. However this germline WGS would offer the possibility to screen for a wide range of genetic conditions, relevant for patients and their families. There are many pros and cons to be considered. The second topic is the mainstreaming of genetic testing, i.e. DNA testing being ordered by non-geneticist clinicians, e.g. medical oncologists and surgeons. Several models are now being tested in the field in various countries, typically for breast cancer. The third topic is the use of polygenic risk scores for cancer, as opposed to the traditional testing of genes for Mendelian, single gene, disorders. Something that was for many years regarded as being a predominantly genetic-epidemiological scientific exercise, is now being adopted for clinical application. Background Individuals with Lynch syndrome (LS), an autosomal dominant inherited cancer syndrome caused by mutations in DNA mismatch repair genes have an increased risk of developing a range of epithelial malignancies, in the absence of a pre-malignant phenotype. Common genetic variants of the TERT gene are associated with telomere length and have been linked to a wide range of cancers, including colorectal cancer (CRC) and with tumours arising in LS. Aim In this study we have genotyped 3 SNPs in TERT; rs2736108 (upstream gene variant), rs2075786 and rs7705526 (both intronic variants), previously shown to influence telomere length in tumours and in association with LS. Methods We genotyped 1895 LS patient samples for rs2075786 (G>A) and 1241 LS patient samples for rs2736108 (C>T) and rs7705526 (C>A) using TaqMan SNP assays (Applied Biosystems). The risk of cancer with each SNPs' genotype was estimated by heterozygous and homozygous odds ratio (OR) using simple logistic regression and mixed-effects logistic regression to adjust for gene, gender and country taking into account family ID (probands and relatives). Results We observed an increased risk of cancer in patients carrying pathogenic MSH2 mutations and the heterozygous genotype (GA) for rs2075786 (OR=1.84, confidence interval (CI) =1.15-2.94), p=0.01). This association is even stronger if patients <45 years of age at diagnosis were compared to cancer free patients; MSH2 and GA for rs2075786 (OR=2.53, CI=1.43-4.49, p=0.002). Conclusion Even though both MLH1 and MSH2 mutation carrier's initially have similar risks of cancer, a SNP in TERT appears to be associated with a differential risk of developing cancer for MSH2 mutation carriers. MSH2 deficiency alone has previously been shown to accelerate telomere shortening in normal human cells and can explain the increased risk in younger heterozygous MSH2 mutation carriers. By including modifier gene/loci in risk algorithms it should be possible to tailor surveillance options for individual patients. The term polyp refers to any tissue hypertrophy from the surface of mucous membranes. Intestinal polyps arise from the mucous membrane of the small and large intestines. The hyperplastic, adenomatous, hamartomatous and inflammatory polyps are main types of polyps observed in gastrointestinal tract. The adenomatous and hamartomatous polyps may occur as symptoms of susceptibility syndromes to the occurrence of neoplastic diseases. The syndromes of inherited predispositions associated with the presence of multiple intestinal polyps include: familial adenomatous polyposis (MIM 175100), Peutz-Jeghers syndrome (MIM 175200), juvenile polyposis syndrome (MIM 174900) and Cowden Syndrome(MIM 153480). The occurrence of these diseases is associated with mutations of the following genes: APC, MUTYH, STK11, BMPR1A, SMAD4 and PTEN. The spectrum of point mutations and copy number variation in genes predisposing to intestinal polyposis in the Polish population were determined. Determination of the spectrum of mutations of predisposition genes in the Polish population allows to optimize mutation detection for the Polish population. The research in part was financed by the project NCN 2013/09 / N / NZ5 / 02505.

A5
Association between mutations in genes from NGS multi-gene panels and breast and ovarian cancer risk Suszynska M 1  Background As BRCA1/2 mutations are responsible for only part of familial breast cancer (BC) and ovarian cancer (OC) cases, researchers and clinicians are looking for other BC/OC risk genes. Recent progress and decreasing cost of the next generation sequencing (NGS) has allowed to expand the range of examined genes. However, the inclusion of additional genes to the NGS multi-gene panels (MGPs), is not always supported by strong genetic or statistical evidences and most of the genes still have to be considered as "candidates". Aim of the study We aimed to estimate a reliable BC and OC risk associated with mutations in genes repeatedly employed in MGPs.

Methods
We accomplished a wide-scale meta-analysis of results from 48 MGPbased studies, that analyzed BC and OC patients. The mutation frequency of~120,000 BC/OC cases and~120,000 controls, extracted from public gnomAD database, were used to estimate BC and OC association with mutations in 37 genes.

Results
In total, 13 and 11 of the analyzed genes were significantly associated with an increased BC and OC risk, respectively. We noticed that mutations in a few genes are attributed to a high BC risk, at a level similar to that of BRCA2 mutations. Furthermore, our results revealed that CDKN2A, not often mentioned in the context of BC, can be classified as a high-risk gene. The other striking observation of our study is the substantial difference in the profile of genes contributing to either BC or OC risk. We showed that mutations in several genes much more strongly predispose to OC than BC. Extreme examples are mutations in RAD51D, RAD51C, and NBN that are specific to OC and do not predispose to BC at all. Additionally, what is equally important, the analysis indicated which genes, frequently used in MGPs, are not associated with BC/OC risk. Conclusions In summary, our results define with high confidence the role of several genes in the genetic predisposition to BC and OC. The practical implication of our results is the support that they provide for a substantively justified interpretation of diagnostic results.
Methylation of CpG islands in promoter region of genes is an epigenetic modification that causes silencing of genes and might be associated with cancer risk if it is present in peripheral blood. It has been suggested that constitutional methylation of BRCA1 promoter correlates with breast cancer risk, especially with triple-negative tumors. In this study we evaluated an association of BRCA1 methylation in peripheral blood with breast cancer risk and assessed correlation with clinical features of tumors. We examined three groups of women: 504 triple-negative breast cancer cases, 438 non-TNBC cases and 500 healthy controls. All women were negative for 13 common Polish BRCA1 germline mutations. Moreover, 274 FFPE tumor tissues were tested to estimate association between constitutional and somatic BRCA1 promoter methylation. Methylation status was assessed using methylation-sensitive high-resolution melting (MS-HRM). Additionally, we genotyped variant c.-107A>T in BRCA1 gene to assess its potential correlation with BRCA1 methylation. The results show that BRCA1 methylation detected in peripheral blood is significantly associated with the risk of TNBC (OR 5.25, p<0.001) and correlates with methylation in paired tumors. The variant c.-107A>T was not detected in tested women from Polish population.
In Poland ovarian cancer represents the second cause of cancer among gynecological malignancies and the fourth cause of cancer deaths among women. Literature data shows that more than one-fifth of ovarian cancer cases have been related to hereditary factors. It has been recognized that the most frequently germline mutation in hereditary ovarian cancer are BRCA1/2 mutations. Nevertheless, several other genes, as RAD51C, have been suggested to be associated with hereditary ovarian cancer. Mutations in other genes which are known to be associated with high breast cancer risk in Polish population, as PALB2 and CHEK2, have not been tested in ovarian cancer patients up to now. The aim of the study is to estimate the frequency of recurrent Polish germline mutations in BRCA1/2, RAD51C, PALB2 and CHEK2 genes among unselected and familial ovarian cancer patients. Additionally, an association of RAD51C, PALB2 and CHEK2 mutations with ovarian cancer risk was assessed. Molecular analyses included genotyping of recurrent mutations in BRCA1/2 (13), RAD51C (3), PALB2 (2) and CHEK2 (3) in a group of 2000 unselected OC,~250 HOC and 2000 healthy controls . The frequency of BRCA1/2 was 11.02%. We found significant association of RAD51C and PALB2 mutations, but not CHEK2 mutations, with ovarian cancer risk. The study was supported by the "Młody Badacz" grant MB-158-219/17

A8
The presence of NOD2 mutation in younger breast cancer patients single center experiences

Introduction
The population risk of breast cancer before the age of 50, associated with the NOD2 mutation, is approximately 1%. It increases 5 times the risk of DCIS <50 years. The purpose of this study was to evaluate the presence of NOD2 (c.3016_3017insC) mutation in younger breast cancer (BC) patients (<45 years) according to clinicopathological factors in comparison to control group. Material We have were analyzed prognostic factors in younger BC patients with confirmed NOD2 (c.3016_3017insC) (n=42) mutation. Control group was selected from BC patients without tested mutations (n=392). The presence of the most common mutations in BRCA1 (c.68_69delAG, c.181T>G, c.4034delA, c.5266dupC, c.3700_3704del5), BRCA2 (c.5946delT and c.9403delC), CHEK2*1100delC or I157T mutations genes were excluded. Mutation analysis was carried by a multiplex allele-specific polymerase chain reaction assay.

Conclusion
The presence of NOD2 mutations (in age <45 years) were associated with younger age of disease diagnosis and gastrointestinal cancer in family history. Breast cancer in family history was characteristic for NOD2 mutation carriers in age>45 years. Luminal A BC subtype was most characteristic for this group.

A9
Clinical and molecular aspects of hereditary breast cancer diagnosis and management: PALB2 and RECQL epidemiology in Latvia, Manchester scoring system and contralateral breast cancer risk reduction Hilz P 1 , Heinrihsone R 1 , Pätzold LA 1 , Qi Q 2 , Trofimovics G 3 , Gailite L 4 , Peteris Loza 1 , Elina Tauvena  Here we are going to present three small studies covering different aspects of hereditary breast cancer management. Large-scale case control studies revealed a number of moderate risk -low frequency breast cancer alleles of the PALB2 and RECQL genes. Some of them reported as founder variants of Central and Eastern Europe. Based on highly similar founder variant spectra of the BRCA1 in Poland and Latvia, we decided to test frequency of other common variants of moderate breast cancer risk -c.509_510delGA (rs515726124) and c.172_175delTTGT (rs180177143) of the PALB2 gene and c.1667_1667+3delAGTA variant of the RECQL gene in breast cancer case-control series from Latvia to gain better understanding of the role of genes in susceptibility to breast cancer and their clinical significance. The calculated frequency for c.509_510delGA of the PALB2 gene in the case group is 0.35% and 0.00% in the control group, with respective relative risk (RR) 7.18 (CI 95% 0.37 -138.75; p = 0.19). As for PALB2 c.172_175delTTGT variant, the frequency in the case group of our study is 0.04%. In the control group of our study non heterozygous carriers were detected, which lead to calculated RR = 1.50 (CI 95% 0.06 -36.83; p-value = 0.80). There were no carriers of the RECQL variant c.1667_1667+3delAGTA identified in our case group and 2 heterozygotes were identified in the control group. The calculated RR = 0.26 (CI 95% 0.01 -5.33; p-value = 0.38).Acquired results on the PALB2 gene variants are able to supplement evidence on the allele frequency in the breast cancer patients. Based on our results we cannot confirm contribution of the RECQL variant c.1667_1667+3delAGTA allele to the breast cancer development. Recent availability of commercial complete BRCA1/2 testing in BRCA1 founder (c.4035delA, c.5266dupC) population like Latvia and relatively high non-founder BRCA1/2 mutations frequency has raised question about the selection criteria for this service, if BRCA1 founder mutations are negative. Wide variety of reasons contributes to low diagnostic accuracy of family cancer history criteria alone in our population. Aim of the study is to evaluate the diagnostic value of Manchester scoring system (MSS). MSS was calculated in 1006 unselected breast cancer cases. 57/1006 (5.7%) MSS positive cases were identified. 24/57 MSS positive cases were BRCA1 founder positive, but 33/57negative. From the other hand there are 36/1006 (3.6%) BRCA1 founder mutation carriers in our cohort. 24/36 has positive MSS and 12/36 negative MSS. Our conclusion is that MSS has higher diagnostic accuracy in comparison to family cancer history alone and 3.3% of unselected MSS positive and BRCA1 founder mutation negative breast cancer cases should undergo complete BRCA1/2 testing as probability of finding pathogenic mutation is more than 10%. BRCA1 positive breast cancer cases has more frequently contralateral breast cancer (CBC) events. The most effective prevention strategy is contralateral risk reductive mastectomy (CRRM). Since 2009 22 CRRMs have been performed in BRCA1 positive unilateral breast cancer cases. Control group consist of 21 BRCA1 positive unilateral breast cancer case without CRRM. Median follow-up since treatment of primary breast cancer is 4.29 +/-0.78 years. There are 5/21 (24%) cases of CBC in the control group, but no CBC events 0/22 (0%) in CRRM group. Our conclusion is that BRCA1 positive breast cancer patients have high frequency of CBC events and CRRM is effective method to reduce CBC events in BRCA1 positive breast cancer cases. Partner and localizer of BRCA 2 (PALB2) was identified as a moderaterisk gene of breast and pancreas cancer .PALB2 mutations are rare. The prevalence of PALB2 mutation is now estimated to be 1,7 % in Southern Poland. The absolute risk of breast cancer in women up to 70 years of age with PALB2 mutation ranges from 33% for women without family histories of breast cancer to 58 % for women with family history. In the present study, one patient with a deleterious mutation of PALB2 (c.509-510delGA) has been identified. The proband was a 47-years old woman was admitted to Institute of Oncology because of enlargement of right breast. Contrast-enhanced MRI of the right breast showed a large high dense soft mass lesion in the outer quadrant and center of the right breast with speculated outline measured (10 x 7,5 cm). Moreover, multiple enlarged axillary lymph nodes were visible. Pathological findings were as follows: invasive ductal carcinoma (cribriform type), histological grade 3,. an estrogen receptorpositive (ER-positive), progesterone receptor-positive (PgR-positive), and human epidermal growth factor receptor 2-positive (HER2-positive) and an estrogen receptor-negative (ER-negative), progesterone receptornegative (PgR-negative), and human epidermal growth factor receptor 2-positive (HER2-positive). The proband had mother who was diagnosed with colon cancer at the age of 65 and maternal brother who was diagnosed with gastric cancer at the age of 55 years. The patient gave written informed consent for the publication of her clinical data. The study of primary-multiple tumors allows us to come closer to understanding both the differences existing between individual tumors, and their similarity, based on the unity of a significant number of risk factors. The aim of the study was to study the clinical and diagnostic features of primary-multiple tumors with ovarian involvement. In 81 patients included in the study, 174 malignant tumors were diagnosed, one of which was localized in the ovaries. Primary multiplicity of neoplasms in most cases was represented by two localizations -70 cases (86%), less often three -10 patients (12%). Often the development of ovarian cancer was combined with breast cancer -27 cases (33%), uterine malignant tumors -23 (28%) and gastrointestinal tract tumors -16 (20%). The study of family history indicates the presence of a hereditary predisposition to the development of tumors in 36 women (44%). Only in 16% of cases relatives of the first line had ovarian and / or breast cancer. Twenty BRCA1 germ-line mutation carriers (25%) were identified by the analysis of the Slavic founder alleles in BRCA1 gene. Among these were the most frequently detected mutations 5382insC (55%) and 4153delA (25%). Among women with breast and ovarian cancer, the mutation in the BRCA1 gene was confirmed in 56% of cases, which confirms the importance of genetic factors in the development of primary-multiple tumors of the female reproductive system. In this work, the characteristics of synchronous and metachronous primary-multiple tumors are presented. When studying the receptor status of BRCA1associated primary-multiple tumors of the ovaries and mammary gland, it was found that most ovarian carcinomas, unlike breast tumors, have a receptor-positive status. A burdened family history and the identification of mutations in the BRCA1 gene should be considered as an integral part of a comprehensive survey of women with malignant neoplasm of the female reproductive system to determine the genetic risk of developing new tumors of the female reproductive system and develop the principles of genetic cancer prevention. Features of the receptor status of BRCA1-related ovarian carcinomas allow each patient to be treated differently, taking into account the genetic and receptor status of a specific tumor. Background Genetic predisposition to papillary thyroid cancer (PTC) is known to be muligenetic and complex with many genes interacting with environmental factor. However, the genes responsible for this predisposition mostly are not known. Many of them were analysed, but only for some genes the association with thyroid cancer is well established. Among analysed genes was CHEK2, but with the relatively small number of 468 PTC cases included. The aim of our study was to analyse the association of c.444+1G>A (formely IVS2+1G>A) CHEK2 variant in the big number of 2279 of PTC cases and 1218 controls. c.444+1G>A variant was analysed with HRM methods and confirmed by Sanger sequencing. The second purpose of the study was to perform the meta-analysis in all available Polish data to summarize c.444+1G>A CHEK2 variant association with PTC. Results A significant association was seen for c.444+1G>A with OR=4.49. Performed meta-analysis have confirmed these results -for c.444+1G>A association was seen with OR=5.89.

Conclusions
We have confirmed the association of c.444+1G>A CHEK2 variants with PTC in Polish population. This work was supported by the National Centre for Research and Development project under the program "Prevention practices and treatment of civilization diseases" STRATEGMED (STRATEGMED2/ 267398 /4/NCBR/2015) and National Science Center, Polish, grant number N N402 193740

A13
Evaluation of the effectiveness of recruitment methods for prophylactic examinations in groups of high-risk cancer patients Galor A 1 , Cezary C, Lubiński J1, Narod SA 2 , Gronwald J 1

Introduction
Literature data indicate that the use of appropriate recruitment methods for prevention programs has an impact on the recruitment and cost effectiveness of these programs. In Poland, the effectiveness of active recruitment methods for preventive screening programs in high-risk cancer groups, which would include gene mutation carriers, has not been evaluated so far Objective The aim of the study was to assess the telephone, postal and combined (letter invitation and subsequent telephone invitation in the absence of responses to a letter invitation) method of invitations to preventive programs in groups of patients at high risk of developing malignant tumors, including recruitment and cost effectiveness.

Material and methods
The research was carried out in the following groups of patients: Group I, 93 males with a BRCA1 gene mutation; Group II, 199 women with a BRCA1 gene mutation; Group III, 1497 women with the pedigree diagnosis of HBC or HBO; Group IV, 419 women with the pedigree diagnosis of HNPCC or LOFCC.In each of the examined groups (Group I-IV), participation in preventive examinations (recruitment effectiveness) depending on the form of the invitation was determined and the economic effectiveness of the patient invitation methods was evaluated. Results 1. The telephone invitation is characterized by the highest recruitment and economic efficiency in all the examined groups (Group I-IV) in comparison to other methods of invitations. 2. Invitation by the letter method is characterized by the lowest recruitment effectiveness and indirect economic effectiveness in all examined groups (Group I-IV). 3. Invitation by the combined method is characterized by similar recruitment effectiveness to the telephone method and is associated with the highest costs incurred in all examined groups (Group I-IV). 4. In the group of women, who carry BRCA1 gene mutation, the highest economic efficiency was observed using all the tested methods and the highest recruitment efficiencyusing the telephone and letter method. 5. The lowest recruitment effectiveness is observed in the group of patients with pedigree diagnosis HNPCC or LOFCC implemented through a letter invitation. 6. The highest recruitment costs are observed in the group of males, carriers of the BRCA1 gene mutation using the combined method. Conclusions 1. The type of invitations method used affects the effectiveness of recruitment for preventive examinations. 2. The type of invitations method used has an impact on the cost effectiveness of recruitment for preventive examinations.
3. Telephone methods should be a recommended way of inviting patients from high-risk cancer groups for prophylactic examinations. 4. In groups of high-risk cancer patients, it is possible to increase economic efficiency and probably recruitment by introducing new methods of invitations using correspondence via email (e-mail) and short message service via mobile telephony (SMS). In this case, the combined method can potentially have an advantage over other methods. Further studies on the effectiveness of these methods are necessary.

A14
Long-term survival of invasive ovarian cancer associated with BRCA1-4153delA mutation in Lithuanian population Elsakov P 1 , Razumas T 3 , Luksyte A 2 , Smailyte G 2 The aim of this study was to estimate 10-year survival for women with invasive ovarian cancer associated with BRCA1-4153delA mutation in a high incidence (Lithuanian) population.

Materials and methods
The study focused on 71 ovarian cancer patients treated at Vilnius University Oncology Institute. Sixty patients (Group I) were consecutive, newly diagnosed cases, unselected for age or family history. Eleven patients (Group II) were selected by strong hereditary criteria with an aggregation of at least three breast/ovarian cancers had Hereditary Breast Ovarian Cancer Syndrome (HBOCS). The founder mutations of BRCA1 carrier status and BRCA2 of these patients were identified. The treatment of all patients was similar as per national protocols for treatment of ovarian cancer cases independent of mutation status. Only a patients alive 10 years after diagnosis were included in the study. Kaplan-Meier survival curves were constructed for the groups: Group Iunselected women with ovarian cancer and Group IIwomen with HBOCS by heredity and BRCA1/2 mutation status. The Log-Rank test was used to evaluate the statistical significance of differences. A p < 0.05 was indicative of a significant statistical difference. Cox-proportional Hazards models were used to estimate Hazard Ratios (HRs) associated with mutation status. Results Overall survival 10-years after diagnosis showed no difference (p=0.4351) with regards to the presence or absence of a BRCA1/2 mutation for patients with invasive ovarian cancer. Ten year survival of those associated with BRCA1-4153delA mutation was similar (p=0.8918) to hereditary cases. Multivariable survival analysis for histologic subtype (serous and other) was also assosiated with a similar prognosis (p=0.579) at 10 years for hereditary and non-hereditary cases [HR=1.34, 95% CI= 0.47 to 3.80].

Conclusion
The results of our study show that the long-term (10 year) survival of patients with invasive ovarian cancer with BRCA 1/2 mutation was associated with a similar (p=0.4351) prognosis to those who were not curriers. The 10-year survival of the HBOCS case patients was similar (p=0.8918) to those associated with BRCA1-4153delA mutation when identical management and treatment were received.

Introduction
There is a lot of literature data showing that metals can affect the development of cancer, including laryngeal cancer. However, their blood / serum levels have not yet been evaluated as a prognostic marker in laryngeal cancer. The aim of the study is a prospective evaluation of the correlation between results of treatment of patients with laryngeal cancer and levels of metals in the blood and serum. Material and methods Study groups: 1) 315 patients treated surgically in the period from July 2009 to February 2017 due to squamous cell carcinoma of the larynx, from whom blood was collected before the beginning of treatment in order to assess the levels of zinc, iron and copper in the serum.
2) 184 patients treated surgically in the period from January 2012 to February 2017 due to squamous cell laryngeal cancer, from whom blood was collected before the beginning of treatment to assess the levels of zinc, iron, copper, arsenic, cadmium, mercury and lead in the whole blood . Clinical information on the age of onset, sex, clinical stage, radiation therapy, chemotherapy and pack-years was collected from all patients.
To determine the levels of the indicated metals, the technique of inductively coupled mass spectroscopy (ICP-MS) was used. The results of the treatment were evaluated on the basis of the number of deaths that occurred during the prospective observation period. The test groups were divided into three parallel subgroups (tertiles) depending on the levels of individual metals. The relationship between blood / serum metal levels and survival was analyzed statistically uni and multivariate, taking into account the influence of age, sex, clinical stage, chemotherapy, radiotherapy and pack-years. Results 1. Zinc level in the serum: statistically significant increased risk of death in patients with the lowest zinc levels (<581 μg /l) in comparison with patients with the highest levels (> 688 μg /l): OR-2.04; p-0.029; HR-2.02; p <0.01. 2. Zinc level in the blood: statistically significant increased risk of death in patients with the lowest zinc levels (<5712 μg /l) in comparison with patients with medium levels (5716-6515 μg /l): OR-3.15; p-0.01; HR-2.58; p <0.01. 3. Cadmium level in the blood: statistically significant increased risk of death in patients with mean cadmium levels (0.84-1.3 μg /l) in comparison with patients with the lowest levels (<83 μg /l): OR-2, 81; p-0.039; HR-2.14; p-0.043. 4. There were no statistically significant differences between the patients' survival and the levels of copper and iron in the serum as well as copper, arsenic, lead and mercury in the blood.

Conclusions
The levels of zinc below 580 μg /l in the serum and below 5700 μg /l in the blood and the level of cadmium above 0.80 μg /l in the blood are associated with an increased risk of death of a patient with laryngeal cancer in Poland. The implementation of chemoprevention modifying the levels of the above-mentioned metals might improve the results of treatment of laryngeal cancer.

Purpose
Although the results of studies in populations with low selenium status indicate an inverse correlation between the selenium concentration in the body and the risk of the lung cancer, the effect of this microelement on survival rate with this disease has not been studied.

Material and methods
We conducted a prospective study of 302 patients diagnosed with lung cancer in Szczecin, Poland. Serum selenium was measured at the time of diagnosis, prior to treatment. Patients were followed from the date of diagnosis until death or up to 80 months. Vital status was obtained by linkage to the Polish National Death Registry.

Results
In the Cox proportional hazards analysis performed for all individuals with lung cancer, the hazard ratio (HR) for death from all causes was 1.25 (95% CI 0.86 to 1.83, P=0.99) for patients in the lowest tertile of serum selenium, compared to those in the highest tertile. Among the patients with stage I of the lung cancer this relationship was significant (HR-2.73; P = 0.01) for selenium level in the lowest tertile (<57 μg/L) compared to tertile 3 (>69 μg/L, reference). The 80 months crude survival after diagnosis was 79.5% (95% CI: 68.5 -92.4%) for individuals in the highest tertile and was 58.1% (95% CI: 45.1 -74.9%) for individuals in the lowest tertile with stage I of lung cancer. Conclusion This study suggests that in patients undergoing treatment with stage I of lung cancer, serum selenium level (>69 μg/L ) may be associated with improved survival.

Background
Zinc is a micronutrient, which is essential for human health, involved in regulation of gene expression, e.g. genes related to cell cycle, apoptosis, response to DNA damage, antioxidant defense, immune response. Literature data on zinc association with cancer risk show inconclusive results. Aim of the study The aim of the study was to evaluate the relationship between zinc blood levels and subsequent cancer risk in a large prospective cohort of persons followed for incident cases of cancer in Szczecin Poland. Material and methods The study was conducted in 3 prospective cohort consisted of persons with no cancer at that baseline: 1. 601 women with BRCA1 mutation, among them 42 cancers were identified during the follow-up 2. 1698 women without BRCA1 mutation, among them 110 cancers were identified during the follow-up 3. 1467 men, among them 42 cancers were identified during the follow-up.
Zinc level blood was measured by inductively coupled plasma mass spectrometry (ICP-MS) using Elan DRC-e ICP-Mass Spectrometer, Perkin Elmer. Odds Ratios were calculated using Fisher's exact test.

Conclusions
Results from this study suggest that blood zinc level is a strong marker of cancer risk. It might be a subject of future studies to establish whether zinc intake modifications changing Zn blood level will be an effective way of cancer prevention.

A18
Copper as marker of cancer risk in BRCA1(+) women in
In the group of women free of any pathogenic variants in DNA repair pathway we showed that higher levels of cadmium in blood might be beneficial for prospective risk of breast cancer risk. Analysis of our biggest cohort revealed that cadmium levels higher than 0,59 μg/l are associated with up to 4 times lower risk of breast cancer (OR= 4,20; p=0,0319; 95%CI:1,01-17,80). Prospective observation of men reveals that lowest quartile of cadmium concentration compared to the sum of the rest quartiles gives us 3 times lower risk for any cancer (OR=0,2974; p=0,0009; 95%CI:0,1424-7,025) Conclusions There is a pending need for cadmium removal therapy in women carrying BRCA1 founder mutation and men. Result from cohort of healthy women without genetic mutations of susceptibility for breast cancer is in opposite to current state of knowledge but it is confirmed in two independent studies. Further research on evaluating breast cancer risk in women without BRCA1 mutation is needed.

Introduction
Trace amounts of arsenic are considered as necessary for normal development of organism. Animals study shows inverse correlation between arsenic and toxic effects. Exclusion of this element from food causes in animals among others depressed growth and abnormal reproduction [1,2]. Arsenic is generally considered as a cancer risk factor (kidney [3], bladder [4], skin [5] and lung cancer [4]). Methods Four prospective groups were analyzed. The cohort of women BRCA1 carriers consists of almost 601 initially unaffected with 42 cases developed during the 4 years of follow-up. The cohort of women BRCA1 non-carriers consists of almost 1698 initially unaffected with 110 cases developed during 5 years of follow-up. The men cohort consists of almost 1467 initially unaffected with 103 cases developed the 2 years of follow-up. Blood arsenic level was measured by ICP-MS Elan DRC-e (PerkinElmer).

Conclusions
Results from this study suggests that arsenic blood level can be the strongest diet marker of cancer risk among women and men in Poland. Diet modifications changing blood arsenic level may be effective way of cancer prevention.