Research status of CHEK2 gene and breast cancer / 中国医师杂志

At present, breast cancer is one of the main causes of death for women in the world. In recent years, the incidence rate of breast cancer in China has also been rising. Existing studies have shown that the most fully studied gene for breast cancer susceptibility is breast cancer susceptibility gene 1/2 (BRCA1/2), and other genes related to the increased risk of breast cancer have also been confirmed, including cell-cycle-checkpoint kinase gene 2 (CHEK2), which is a tumor suppressor gene encoding serine/Threonine kinase CHEK2. The gene is involved in DNA repair, cell cycle regulation, apoptosis and other DNA damage response pathways. This article reviews the research status of CHEK2 gene and its important role in the prevention, diagnosis and treatment of breast cancer.

Tests genéticos brca1/2 y otros genes de predisposición al cáncer de mama: análisis retrospectivo de 106 pacientes / Genetic studies for brca1/2 and other genes related to predisposition in breast cancer: retrospective analysis of 106 patients

Introducción Si bien el cáncer de mama hereditario representa entre el 5-10% del total de los cánceres de mama, es importante la detección de pacientes portadoras de mutaciones patogénicas en genes brca1/2 y otros genes relacionados con el cáncer de mama ya que esta información permitirá tomar conductas adecuadas de prevención y/o tratamiento tanto en la paciente portadora como en sus familiares. Objetivo Llevar a cabo un análisis retrospectivo de 106 pacientes que realizaron estudios genéticos para genes brca1/2 y otros genes relacionados con el cáncer de mama. Resultados Del total de 106 pacientes, encontramos: 17 (16,03%) con mutación patogénica; 38 (35,85%) con vus (Variantes de significado incierto) informadas en el reporte original; y 51 (48,11%) con estudios negativos. De los 38 informes con vus, 7 (6,6%) fueron reclasificadas como vus verdaderas a junio de 2018. De las 17 mutaciones patogénicas encontradas, 16 correspondieron a mutaciones en los genes brca1/2 (15,09%) y 1 a mutación en el chek2 (3,77%). Conclusiones Los estudios genéticos de predisposición en cáncer de mama son, en la actualidad, una herramienta fundamental para la atención multidisciplinaria de la paciente de alto riesgo en un consultorio de patología mamaria. Es un deber del mastólogo pensar en la indicación de un estudio genético de predisposición al cáncer de mama y derivar al genetista para identificar correctamente al paciente que se va a beneficiar de esta información

Introduction Although hereditary breast cáncer represents 5-10% of all breast cancers, it is important to detect patients carrying pathogenic mutations in brca1/2 genes and other genes related to breast cáncer as this information will allow take appropriate prevention and / or treatment behaviors in both the patient carrier and their family members. Objective To make a retrospective analysis of 106 patients who carried out genetic studies for brca1/2 genes and other genes related to breast cancer. Results From 106 patients we found 17 (16.03%) with pathogenic mutations, 38 (35.85%) with vus (variant of unknown significance) in the original report, and 51 (48.11%) negatives. From 35 vus, we reclasified as true vus only 7 (6,6%) in June 2018. From 17 pathogenic mutations in 106 patients studied (16.03%), we found 16 in the brca1/2 genes (15.09%) and 1 mutation in chek2 (3.77%). Conclusions Genetic predisposition tests in breast cáncer are a fundamental tool for multidisciplinary care of the high-risk patient in a breast center query. The mastologist has to think in the first place about the indication of a genetic testing ofbreast cancer predisposition, and refer to the geneticist for a prompt consultation for patients benefit

The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland. MATERIALS AND METHODS: In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes. RESULTS: A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026). CONCLUSION: The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome.

CHEK2 gene and breast cancer / 国际肿瘤学杂志

CHEK2 is an important susceptibility gene of breast cancer. CHEK2 gene mutations are related to pathologic features and prognosis of breast cancer. So the test of CHEK2 gene mutations may be has certain indication role in the treatment of breast cancer. However, the role of CHEK2 gene mutations in Chinese population still needs further research.

Frequency of the CHEK2 1100delC Mutation in Korean Women with Early Onset Breast Cancer / 한국유방암학회지

PURPOSE: Sequence variants in the cell cycle checkpoint kinase 2 (CHEK2 1100delC) are associated with an increased risk for breast cancer in women carrying this mutation. It is a lowpenetrance breast cancer susceptibility allele, frequently observed in patients with a family history of breast cancer and/or young age, with the frequency varying according to race or ethnicity. In this study, we evaluated the significance of CHEK2 1100delC in predisposition to breast cancer by assessing its frequency in material from 101 Korean women patients with early-onset breast cancer. METHODS: One hundred and one Korean patients with earlyonset breast cancer (40 yr old or younger) were selected for this study. All the patients had been screened for BRCA1 and BRCA2 mutations and 14 patients had deleterious mutations. Of the 101 patients entered for this study, 14 had family history of breast cancer and 7 had bilateral breast cancers. Mutation detection of CHEK2 1100delC was based on analysis of primer extension products generated from previously-amplified genomic DNA using a chip based MALDI-TOP mass spectrometry platform (Sequenom, Inc., San Diego, CA, USA). RESULTS: None of the 101 Korean patients with a family history of breast cancer and early-onset breast cancer who were candidates for the BRCA1 and BRCA2 test carried the 1100 delC mutation, which is observed in Caucasians with limited frequency. CONCLUSION: We previously observed higher or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasians. However, the CHEK2 1100delC mutation is absent or infrequent in Korean patients with breast cancer who have a high risk of BRCA1 and BRCA2 mutations, making its screening irrelevant.