Epidemiologic, clinical, and molecular characteristics of hereditary prostate cancer in Latvia

Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background and Objective. Prostate cancer is one of the most commonly diagnosed malignancy affecting men in Latvia. The aim of this study was to evaluate the epidemiological features and molecular basis of hereditary prostate cancer in Latvia. Material and Methods. A total of 1217 newly diagnosed prostate cancer patients were recruited in our study. Data were analyzed according to clinical diagnostic criteria for hereditary prostate cancer. Molecular testing for the founder mutation 657del5 of the NBS1 gene was performed for the first 280 prostate cancer patients and 173 control cases, and for the founder mutations 300T/G, 4153delA, and 5382insC of the BRCA1 gene for 112 prostate cancer patients with a history of breast or ovarian cancer in their families. Results. Of the 1217 families, 14 (1.2%; 95% CI, 0.7%-1.9%) matched clinical diagnostic criteria for definitive hereditary prostate cancer, and of the 1217 families, 196 (16.1%; 95% CI, 14.1%-18.3%) for suspected hereditary prostate cancer. The founder mutation of the NBS1 gene was detected in 1 (0.4%, 95% CI, 0.1%-2.0%) of the 280 cases in the prostate cancer group and in 1 (0.6%; 95% CI, 0.1%-3.2%) of the 173 cases in the control group. The mutation 5382insC of the BRCA1 gene was detected in 2 (1.8%; 95% CI, 0.5%-6.3%) of the 112 cases analyzed in the prostate cancer group. No other BRCA1 founder mutations were detected. Conclusions. Our study did not reveal predisposition genes for hereditary prostate cancer as the founder mutations of the BRCA1 and NBS1 genes are rarely detected in Latvia, but showed the importance of evaluation risk individually as a positive family history of cancer was associated with the earlier onset of prostate cancer.publishersversionPeer reviewe

The first evidence of hereditary and familial gastric cancer in Latvia : Implications for prevention

Background and Objective: Gastric cancer is a frequent cause of cancer mortality. The prognosis of established tumor is unfavorable due to the propensity to spread and limited treatment efficiency. Therefore, prevention has a high significance. We tested a population screening approach in order to identify families with an increased gastric cancer load for further surveillance. Material and Methods: Population screening was performed by questionnaire reaching 76.6% of the population. Hereditary gastric cancer (HGC) syndrome was diagnosed if 3 mutually first-degree relatives with gastric cancer were reported in the kindred. Additional group (HGC2) of families with 2 first-degree relatives affected by gastric cancer was identified. Results: The HGC syndrome was diagnosed in 0.11%, but HGC2 syndrome, in 0.4% probands. The gastric cancer frequency among blood relatives was 25.2% (95% CI, 20.6%-30.4%) in HGC, but 16.0% (95% CI, 13.8%-18.5%) in HGC2 families. The mean age at diagnosis of cancer was 56.9 years (95% CI, 53.4-60.3) in HGC and 62.5 years (95% CI, 60.1-64.8) in HGC2. The mean survival was 2.6 years (95% CI, 1.2-4.0). Conclusions: Population screening identifies reasonable number of families with a high frequency of gastric cancer. The frequency of gastric cancer and an unfavorable course characterized by low survival justify surveillance in families with 2 or 3 first-degree relatives affected by gastric cancer. Population screening provides the age characteristics of the respective tumors in order to adjust the surveillance schedule.publishersversionPeer reviewe

Population screening for hereditary and familial cancer syndromes in Valka district of Latvia

<p>Abstract</p> <p>Background</p> <p>The growing possibilities of cancer prevention and treatment as well as the increasing knowledge about hereditary cancers require proper identification of the persons at risk. The aim of this study was to test the outcome of population screening in the scientific and practical evaluation of hereditary cancer.</p> <p>Methods</p> <p>Population screening for hereditary cancer was carried out retrospectively in a geographic area of Latvia. Family cancer histories were collected from 18642 adults representing 76.6% of the population of this area. Hereditary cancer syndromes were diagnosed clinically. Molecular testing for <it>BRCA1 </it>founder mutations 300 T/G, 4153delA and 5382insC was conducted in 588 persons who reported at least one case of breast or ovary cancer among blood relatives.</p> <p>Results</p> <p>Clinically, 74 (0.40%; 95% confidence interval (CI): 0.32 - 0.50%) high-risk and 548 (2.94%, 95% CI: 2.71 - 3.19) moderate-risk hereditary cancer syndromes were detected covering wide cancer spectrum. All syndromes were characterised by high cancer frequency among blood relatives ranging 8.6 - 46.2% in contrast to spouse correlation of 2.5 - 3.6%. The mean age of cancer onset ranged 38.0 - 72.0 years in different syndromes. The <it>BRCA1 </it>gene mutations were identified in 10 (1.7%; 95% CI: 0.9 - 3.1%) probands. Families with established BRCA1 gene founder mutations were identified with the frequency 1:2663 clinically screened persons.</p> <p>Conclusions</p> <p>Population screening is a useful practical tool for the identification of persons belonging to families with high frequency of malignant tumours. The whole hereditary and familial cancer spectrum along with the age structure was identified adjusting follow-up guidelines. Another benefit of the population screening is the possibility to identify oncologically healthy persons belonging to hereditary and familial cancer families so that appropriate surveillance can be offered. Clinical diagnostics is appropriate for population screening purposes; molecular investigation provides additional information. In collaboration with family doctors, the screening is technically manageable as characterised by high compliance.</p

Effectiveness of Secondary Risk–Reducing Strategies in Patients with Unilateral Breast Cancer with Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery : Evidence-Based Simulation Study

Funding Information: JM, DP, and MJC conceptualized this study. JM curated the data. PRP performed formal analysis of the study data. JG and FC were responsible for funding acquisition and project administration. JM and PRP proposed the study methodology and wrote the manuscript. MJC, EM, and GT were responsible for acquisition of resources and study supervision. PRP performed software/statistical analysis. JM, PRP, MN-M, MJC, and FC validated the study. JM, MN-M, MJC, EM, and GT performed data visualization. JM, MN-M, MJC, EM, and FC reviewed and edited the manuscript. Publisher Copyright: ©Jelena Maksimenko, Pedro Pereira Rodrigues, Miki Nakazawa-Miklaševiča, David Pinto, Edvins Miklaševičs, Genadijs Trofimovičs, Jānis Gardovskis, Fatima Cardoso, Maria João Cardoso.Background: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. Objective: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. Methods: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk–reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Results: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk–reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Conclusions: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.publishersversionPeer reviewe

Allelic variants of breast cancer susceptibility genes PALB2 and RECQL in the Latvian population

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Role of percutaneous needle biopsy of axillary lymph nodes to evaluate node positive breast cancer after neoadjuvant chemotherapy

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