Hereditary Cancer in Clinical Practice最新文献

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Possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients. 甲状腺癌患者的癌症家族易感性与氧化应激水平之间可能存在联系。
IF 2 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-08-23 DOI: 10.1186/s13053-024-00287-3
Ivane Javakhishvili, Kote Mardaleishvili, Maka Buleishvili, Maia Mantskava, Irakli Chkhikvishvili, Sophio Kalmakhelidze, Nina Kipiani, Tamar Sanikidze
{"title":"Possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients.","authors":"Ivane Javakhishvili, Kote Mardaleishvili, Maka Buleishvili, Maia Mantskava, Irakli Chkhikvishvili, Sophio Kalmakhelidze, Nina Kipiani, Tamar Sanikidze","doi":"10.1186/s13053-024-00287-3","DOIUrl":"10.1186/s13053-024-00287-3","url":null,"abstract":"<p><strong>Background: </strong>Hereditary cancer is estimated to account for up to 10% of the worldwide cancer burden; 5% of all thyroid cancers are thought to be genetic. Inheritance of a deleterious mutation in genes associated with a high lifetime risk of developing cancer. Cancer-predisposing genes can promote the initiation and progression of thyroid cancer by enhancing the activation of major signaling pathways through oxidative stress mechanisms.</p><p><strong>Aim: </strong>Identification of the possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients.</p><p><strong>Methods: </strong>Patients with thyroid cancer (with and without genetic predisposition) were investigated. Study participants were treated in Limited Liability Company (LLC) \"Oncology Scientific Research Center\" (Tbilisi, Georgia). The study group was collected between 2020 and 2021. In patients' blood, the thyroid hormones content (free Triiodothyronine (fFT3), free Thyroxine (fFT4), bound Triiodothyronine (FT3), bound Thyroxine (FT4), Thyroid-stimulating hormone (TSH)), and oxidative stress intensity (total activity of non-enzymatic antioxidant system (TAA) and the lipid peroxidation product, malondialdehyde (MDA), content) were investigated.</p><p><strong>Results: </strong>The difference in free and bound forms of T3 and T4 levels in the blood serum between patients with thyroid cancer (Group 2 and Group 3) and the control group (Group 1) was not statistically significant (F<sub>1,2</sub>=0.5, p<sub>1,2</sub>=0.8, F<sub>1,3</sub>=2.31, p<sub>1,3</sub>=0.16). In patients with thyroid cancer the TSH level significantly increased compared to the control group (Group 1) (TSH (mean ± Std error): Group 1- 1.21 ± 0.12, Group 2-2.45 ± 0.11 (F<sub>1,2</sub>=107, p<sub>1,2</sub><0.001), Group 3-2.47 ± 0.17 (F<sub>1,3</sub>=150, p<sub>1,3</sub><0.001)) and the MDA levels increased by 4-5 fold. In patients with thyroid cancer from families with cancer aggregation(Group 2), the level of TAA statistically significantly decreased (F<sub>1 - 2</sub>=200; p<sub>1 - 2</sub><0.001), in patients without genetic predisposition to cancer(Group 3), the level of TAA did not change compared to the control (F<sub>1 - 3</sub>= 2.13; p<sub>1 - 3</sub>=0.15), CONCLUSIONS: Oxidative stress plays a critical role in tumorigenesis, and antioxidant/oxidant imbalance may contribute to the malignant transformation of normal tissue. In patients with familial susceptibility to cancer mutations of several genes, which are involved in the regulation of oxidative metabolism, may contribute to the disruption of the redox balance, increase the level of oxidative stress, and contribute to the development of thyroid cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"15"},"PeriodicalIF":2.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Universal testing in endometrial cancer in Sweden. 瑞典子宫内膜癌的普遍检测。
IF 2 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-08-22 DOI: 10.1186/s13053-024-00288-2
Emil Andersson, Anne Keränen, Kristina Lagerstedt-Robinson, Sam Ghazi, Annika Lindblom, Emma Tham, Miriam Mints
{"title":"Universal testing in endometrial cancer in Sweden.","authors":"Emil Andersson, Anne Keränen, Kristina Lagerstedt-Robinson, Sam Ghazi, Annika Lindblom, Emma Tham, Miriam Mints","doi":"10.1186/s13053-024-00288-2","DOIUrl":"10.1186/s13053-024-00288-2","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes.</p><p><strong>Methods: </strong>IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those.</p><p><strong>Results: </strong>In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS.</p><p><strong>Conclusions: </strong>Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"14"},"PeriodicalIF":2.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Benefits of osimertinib treat a lung adenocarcinoma patient with germline EGFR T790M, somatic EGFR 19-Del, TP53 and PIK3CA mutations. 奥西美替尼治疗患有胚系表皮生长因子受体 T790M、体细胞表皮生长因子受体 19-Del、TP53 和 PIK3CA 突变的肺腺癌患者的疗效。
IF 2 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-08-19 DOI: 10.1186/s13053-024-00286-4
Yingxue Li, Guangqi Li, Zheng Zheng, Wenjuan Wen, Haihui Zhao, Xia Liu, Jiaping Xie, Lin Han
{"title":"Benefits of osimertinib treat a lung adenocarcinoma patient with germline EGFR T790M, somatic EGFR 19-Del, TP53 and PIK3CA mutations.","authors":"Yingxue Li, Guangqi Li, Zheng Zheng, Wenjuan Wen, Haihui Zhao, Xia Liu, Jiaping Xie, Lin Han","doi":"10.1186/s13053-024-00286-4","DOIUrl":"10.1186/s13053-024-00286-4","url":null,"abstract":"<p><strong>Background: </strong>Somatic mutations in the EGFR gene occur in about 50% of non-small cell lung cancers, with the T790M mutation significantly contributing to secondary resistance against EGFR-TKI drugs. However, EGFR T790M germline mutations rarely occur.</p><p><strong>Case presentation: </strong>In this study, we report a case of a lung adenocarcinoma family lineage linked to a germline EGFR T790M mutation. The main subject was diagnosed with stage IV lung adenocarcinoma and experienced a 19-month period without disease progression while treated with Osimertinib. We collected both clinicopathological and familial data from a patient with lung adenocarcinoma. Next-generation sequencing of 40 key genes was performed on the proband's tumor tissue. To detect EGFR germline mutations, Sanger sequencing was conducted on peripheral blood mononuclear cells from the proband and his two daughters. Mutations such as EGFR T790M, EGFR 19-Del, TP53, and PIK3CA were identified in the proband's lung cancer tissue. Additionally, germline EGFR T790M mutations were confirmed in the proband and his daughters through sequencing of their peripheral blood samples. CT scans revealed multiple pulmonary nodules in both daughters.</p><p><strong>Conclusions: </strong>These observations suggest that germline mutations in EGFR T790M could be strongly linked to a familial predisposition to lung cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"13"},"PeriodicalIF":2.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastrointestinal manifestations in patients with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a systematic review with analysis of individual patient data 胃腺癌和胃近端息肉病(GAPPS)患者的胃肠道表现:系统回顾与患者个体数据分析
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-07-22 DOI: 10.1186/s13053-024-00284-6
PA Skat-Rørdam, Y Kaya, N Qvist, TvO Hansen, TD Jensen, JG Karstensen, AM Jelsig
{"title":"Gastrointestinal manifestations in patients with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a systematic review with analysis of individual patient data","authors":"PA Skat-Rørdam, Y Kaya, N Qvist, TvO Hansen, TD Jensen, JG Karstensen, AM Jelsig","doi":"10.1186/s13053-024-00284-6","DOIUrl":"https://doi.org/10.1186/s13053-024-00284-6","url":null,"abstract":"Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant syndrome characterized by fundic gland polyps (FGP) as well as an increased risk of gastric cancer. The syndrome has been recognized as a clinical entity for less than a decade. A clinical suspicion may be complex and can vary from incidental findings of FGPs at gastroscopy to obstructive symptoms with dyspepsia and vomiting. The diagnosis is established by genetic detection of a pathogenic variant in the promotor 1B region of the APC gene. As of yet there are no established clinical criteria for the diagnosis. To increase knowledge of the condition and to discuss possible genetic testing and surveillance strategies, we performed a systematic review of all reported patients with GAPPS. This review was organized according to PRISMA guidelines. The search, which was conducted on September 7th, 2023, was applied to MEDLINE and restricted to only humans and papers in the English language. Only the studies on patients/families with GAPPS verified by identification of a pathogenic variant in the APC promoter 1B were included. Twelve publications with a total of 113 patients were identified. In all instances the diagnosis was genetically verified with reports of four different variants within the APC promotor 1B region. Eighty-eight patients (90.1%) had gastric polyps, of these seven patients had low-grade dysplasia and five patients had both low- and high-grade dysplasia. Thirty-seven patients (45.7%) underwent gastrectomy. There were no reports of duodenal polyps (0%). Gastric cancer was found in 31 patients (30.1%) with a median age of 48 years (range 19–75). Twenty-six patients died (23.2%) of which 19 had developed gastric cancer (73.1%). One patient was diagnosed with metastatic colorectal cancer (2.2%) and died at 73 years of age. Nineteen patients had colorectal manifestations with < 20 polyps (41.3%). Patients with a pathogenic variant in the APC promoter 1B region have an increased risk of gastric polyposis and early-onset gastric cancer. However, there is considerable variation in clinical expression and penetrance, which makes decisions on surveillance and the timing of prophylactic gastrectomy challenging.","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"35 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141741335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report. 两个日本家族性胰腺癌患者疑似 CDKN2A 致病变体:病例报告。
IF 2 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-07-03 DOI: 10.1186/s13053-024-00283-7
Yoshimi Kiyozumi, Hiroyuki Matsubayashi, Akiko Todaka, Ryo Ashida, Seiichiro Nishimura, Nobuhiro Kado, Satomi Higashigawa, Rina Harada, Eiko Ishihara, Yasue Horiuchi, Goichi Honda, Hirotsugu Kenmotsu, Masakuni Serizawa, Kenichi Urakami
{"title":"Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report.","authors":"Yoshimi Kiyozumi, Hiroyuki Matsubayashi, Akiko Todaka, Ryo Ashida, Seiichiro Nishimura, Nobuhiro Kado, Satomi Higashigawa, Rina Harada, Eiko Ishihara, Yasue Horiuchi, Goichi Honda, Hirotsugu Kenmotsu, Masakuni Serizawa, Kenichi Urakami","doi":"10.1186/s13053-024-00283-7","DOIUrl":"10.1186/s13053-024-00283-7","url":null,"abstract":"<p><strong>Background: </strong>Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.</p><p><strong>Case presentation: </strong>The first case is a 74-year-old woman with a diagnosis of pancreatic carcinoma with multiple liver metastases. She had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. Whole exon sequencing detected a germline CDKN2A variant evaluated as likely pathogenic. The results were disclosed to her daughters after she died, and the same CDKN2A variant was detected in one of the daughter. The daughter was referred to a nearby hospital for her clinical management. The second case is a 65-year-old man with pancreatic ductal adenocarcinoma. He had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. He underwent a comprehensive genomic profiling test using pancreatic cancer tissue, and detected a presumed germline pathogenic variant of CDKN2A. Germline testing confirmed the same CDKN2A variant. Genetic analysis of his relatives produced negative results. Other blood relatives are scheduled for genetic analysis in the future. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.</p><p><strong>Conclusions: </strong>In current Japanese precision medicine, comprehensive genetic analysis can reveal rare genetic syndromes and offer us the opportunity to provide health management for patients and their relatives. However, gene-specific issues are raised in terms of the evaluation of a variant's pathogenicity and the extent of surveillance of the at-risk organs due to a lack of genetic and clinical data concerning CDKN2A variant carriers in Japan.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"11"},"PeriodicalIF":2.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey. 林奇综合征患者中可改变的癌症风险因素:一项国际横断面调查。
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-06-14 DOI: 10.1186/s13053-024-00280-w
Robert F Power, Damien E Doherty, Roberta Horgan, Pat Fahey, David J Gallagher, Maeve A Lowery, Karen A Cadoo
{"title":"Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey.","authors":"Robert F Power, Damien E Doherty, Roberta Horgan, Pat Fahey, David J Gallagher, Maeve A Lowery, Karen A Cadoo","doi":"10.1186/s13053-024-00280-w","DOIUrl":"10.1186/s13053-024-00280-w","url":null,"abstract":"<p><strong>Background: </strong>Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention.</p><p><strong>Methods: </strong>A cross-sectional study was carried out utilizing survey methodology. Following public and patient involvement, the survey was disseminated through patient advocacy groups and by social media. Self-reported demographic and health behaviours were collected in April 2023. Guidelines from the World Cancer Research Fund (WCRF) were used to compare percentage adherence to 9 lifestyle recommendations, including diet, physical activity, weight, and alcohol intake. Median adherence scores, as a surrogate for lifestyle risk, were calculated and compared between groups.</p><p><strong>Results: </strong>156 individuals with Lynch syndrome participated from 13 countries. The median age was 51, and 54% were cancer survivors. The mean BMI was 26.7 and the mean weekly duration of moderate to vigorous physical activity was 90 min. Median weekly consumption of ethanol was 60 g, and 3% reported current smoking. Adherence to WCRF recommendations for cancer prevention ranged from 9 to 73%, with all but one recommendation having < 50% adherence. The median adherence score was 2.5 out of 7. There was no significant association between median adherence scores and age (p = 0.27), sex (p = 0.31), or cancer history (p = 0.75).</p><p><strong>Conclusions: </strong>We have characterised the modifiable risk profile of people living with Lynch syndrome, outlining targets for intervention based on lifestyle guidelines for the general population. As evidence supporting the relevance of modifiable factors in Lynch syndrome emerges, behavioural modification may prove an impactful means of cancer prevention.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"10"},"PeriodicalIF":1.7,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A second hereditary cancer predisposition syndrome in a patient with lynch syndrome and three primary cancers. 一名患有林奇综合征和三种原发性癌症的患者出现了第二种遗传性癌症易感综合征。
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-06-12 DOI: 10.1186/s13053-024-00281-9
Annmarie Taheny, Haylie McSwaney, Julia Meade
{"title":"A second hereditary cancer predisposition syndrome in a patient with lynch syndrome and three primary cancers.","authors":"Annmarie Taheny, Haylie McSwaney, Julia Meade","doi":"10.1186/s13053-024-00281-9","DOIUrl":"10.1186/s13053-024-00281-9","url":null,"abstract":"<p><p>Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient's family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A > G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient's screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"8"},"PeriodicalIF":1.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer. 感染幽门螺杆菌的慢性胃炎、肠型胃癌和家族性胃癌患者的基因突变。
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-06-12 DOI: 10.1186/s13053-024-00282-8
Andrzej Hnatyszyn, Marlena Szalata, Aleksandra Zielińska, Karolina Wielgus, Mikołaj Danielewski, Piotr Tomasz Hnatyszyn, Andrzej Pławski, Jarosław Walkowiak, Ryszard Słomski
{"title":"Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer.","authors":"Andrzej Hnatyszyn, Marlena Szalata, Aleksandra Zielińska, Karolina Wielgus, Mikołaj Danielewski, Piotr Tomasz Hnatyszyn, Andrzej Pławski, Jarosław Walkowiak, Ryszard Słomski","doi":"10.1186/s13053-024-00282-8","DOIUrl":"10.1186/s13053-024-00282-8","url":null,"abstract":"<p><strong>Background: </strong>Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments.</p><p><strong>Methods: </strong>Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients.</p><p><strong>Results: </strong>Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene.</p><p><strong>Conclusions: </strong>The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"9"},"PeriodicalIF":1.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes. 结肠镜监测下的结直肠腺瘤和癌症发生率表明,在四种林奇综合征中,有三种会加速 "大爆炸",从而导致癌症。
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-05-13 DOI: 10.1186/s13053-024-00279-3
Pål Møller, Saskia Haupt, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Lone Sunde, Toni Seppälä, John Burn, Inge Bernstein, Gabriel Capella, D Gareth Evans, Annika Lindblom, Ingrid Winship, Finlay Macrae, Lior Katz, Ido Laish, Elez Vainer, Kevin Monahan, Elizabeth Half, Karoline Horisberger, Leandro Apolinário da Silva, Vincent Heuveline, Christina Therkildsen, Charlotte Lautrup, Louise L Klarskov, Giulia Martina Cavestro, Gabriela Möslein, Eivind Hovig, Mev Dominguez-Valentin
{"title":"Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated \"Big Bang\" pathway to CRC in three of the four Lynch syndromes.","authors":"Pål Møller, Saskia Haupt, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Lone Sunde, Toni Seppälä, John Burn, Inge Bernstein, Gabriel Capella, D Gareth Evans, Annika Lindblom, Ingrid Winship, Finlay Macrae, Lior Katz, Ido Laish, Elez Vainer, Kevin Monahan, Elizabeth Half, Karoline Horisberger, Leandro Apolinário da Silva, Vincent Heuveline, Christina Therkildsen, Charlotte Lautrup, Louise L Klarskov, Giulia Martina Cavestro, Gabriela Möslein, Eivind Hovig, Mev Dominguez-Valentin","doi":"10.1186/s13053-024-00279-3","DOIUrl":"10.1186/s13053-024-00279-3","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes.</p><p><strong>Materials and methods: </strong>We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms.</p><p><strong>Results: </strong>Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers.</p><p><strong>Conclusions: </strong>Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"6"},"PeriodicalIF":1.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations. 携带 BRCA1 或 BRCA2 基因突变的女性患皮肤癌的风险。
IF 1.7 4区 医学
Hereditary Cancer in Clinical Practice Pub Date : 2024-05-13 DOI: 10.1186/s13053-024-00277-5
Steven A Narod, Kelly Metcalfe, Amy Finch, An-Wen Chan, Susan Randall Armel, Amber Aeilts, Andrea Eisen, Beth Karlan, Louise Bordeleau, Nadine Tung, William D Foulkes, Susan L Neuhausen, Charis Eng, Olufunmilayo Olopade, Dana Zakalik, Fergus Couch, Carey Cullinane, Tuya Pal, Ping Sun, Joanne Kotsopoulos
{"title":"The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations.","authors":"Steven A Narod, Kelly Metcalfe, Amy Finch, An-Wen Chan, Susan Randall Armel, Amber Aeilts, Andrea Eisen, Beth Karlan, Louise Bordeleau, Nadine Tung, William D Foulkes, Susan L Neuhausen, Charis Eng, Olufunmilayo Olopade, Dana Zakalik, Fergus Couch, Carey Cullinane, Tuya Pal, Ping Sun, Joanne Kotsopoulos","doi":"10.1186/s13053-024-00277-5","DOIUrl":"10.1186/s13053-024-00277-5","url":null,"abstract":"<p><strong>Background: </strong>It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations.</p><p><strong>Methods: </strong>We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up.</p><p><strong>Results: </strong>During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer.</p><p><strong>Conclusion: </strong>The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"7"},"PeriodicalIF":1.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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