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Adrenal tumours in patients with pathogenic APC mutations: a retrospective study. 致病性 APC 基因突变患者的肾上腺肿瘤:一项回顾性研究。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-09-03 DOI: 10.1186/s13053-024-00289-1
Lyman Lin, Victoria Beshay, Finlay Macrae

Background: Adrenal tumours are associated with familial adenomatous polyposis (FAP). In the literature, most studies use the clinical definition of FAP (more than 100 adenomatous polyps found in endoscopic studies). However, not all patients that meet clinical criteria for FAP carry pathogenic mutations in the adenomatous polyposis coli (APC) gene, as there is genetic heterogeneity responsible for FAP with the polyposis sometimes explained by genetic and environmental factors other than pathogenic APC mutations. Reciprocally, not all the patients with pathogenic APC variants will fulfil the classic criteria of FAP.

Objective: This study aims to investigate the characteristics of adrenal tumours in patients with pathogenic or likely pathogenic APC variants and explore the hormonal function of these patients.

Method: This is a retrospective cohort study. Patients with pathogenic or likely pathogenic APC variants were recruited and their radiological assessments were reviewed. Patient demographic data, APC variants, adrenal mass characteristics and hormonal testing results were collected.

Result: The prevalence of adrenal mass was 26.7% (24/90) among patients with pathogenic or likely pathogenic APC variants. Using the classic definition, the prevalence was 32.4% (22/68). Four patients had adrenal hormone testing, two of which had Conn's syndrome and two had nonspecific subclinical results.

Conclusion: In our cohort, the prevalence of adrenal tumours among patients with pathogenic and likely pathogenic APC mutations is at least twice to three times higher than the general population prevalence reported from international population-based studies. The hormonal functions of patients with pathogenic APC variants and adrenal tumours can be investigated with routine testing in further research.

背景:肾上腺肿瘤与家族性腺瘤性息肉病(FAP)有关:肾上腺肿瘤与家族性腺瘤性息肉病(FAP)有关。在文献中,大多数研究都采用了 FAP 的临床定义(在内窥镜检查中发现超过 100 个腺瘤性息肉)。然而,并非所有符合 FAP 临床标准的患者都携带大肠腺瘤性息肉病(APC)基因的致病突变,因为 FAP 存在遗传异质性,息肉病有时可由 APC 致病突变以外的遗传和环境因素解释。反过来说,并非所有具有致病性 APC 变异的患者都符合 FAP 的典型标准:本研究旨在调查具有致病性或可能具有致病性 APC 变异的患者肾上腺肿瘤的特征,并探讨这些患者的激素功能:这是一项回顾性队列研究。方法:这是一项回顾性队列研究,研究人员招募了具有致病性或可能具有致病性 APC 变异的患者,并对他们的放射学评估进行了回顾。收集了患者的人口统计学数据、APC变体、肾上腺肿块特征和激素检测结果:结果:在具有致病性或可能致病的 APC 变体的患者中,肾上腺肿块的患病率为 26.7%(24/90)。根据经典定义,发病率为 32.4%(22/68)。四名患者进行了肾上腺激素检测,其中两人患有康恩综合征,两人有非特异性亚临床结果:结论:在我们的队列中,致病性和可能致病性APC突变患者的肾上腺肿瘤发病率比国际人群研究报告的普通人群发病率至少高出两到三倍。在进一步的研究中,可以通过常规检测来调查致病性APC变异和肾上腺肿瘤患者的激素功能。
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引用次数: 0
Fear of cancer recurrence in breast cancer survivors carrying a BRCA1 or 2 genetic mutation : a cross-sectional study. 携带 BRCA1 或 2 基因突变的乳腺癌幸存者对癌症复发的恐惧:一项横断面研究。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-27 DOI: 10.1186/s13053-024-00285-5
Alexandra Michel, Michel Dorval, Jocelyne Chiquette, Josée Savard

Background: Fear of cancer recurrence (FCR) affects virtually all patients who have been treated for cancer, to varying degrees. Breast cancer survivors who carry a BRCA1 or BRCA2 gene mutation are at high risk of cancer recurrence. No study has yet assessed FCR specifically in this population.

Objectives: This cross-sectional study, conducted in women who were treated for breast cancer and carrying a BRCA1/2 mutation, aimed to: (1) assess the mean level of FCR and estimate the proportion of patients with clinical levels of FCR; (2) examine the relationships between FCR and selected psychological variables (e.g., avoidance, intolerance to uncertainty) and quality of life; (3) explore whether FCR levels vary as a function of the past preventive treatment received; and (4) to assess the associations between FCR and the presence of decisional conflict or regret regarding the various preventive options.

Method: Participants were recruited through an e-mail sent to an oncogenetic network mailing list (Réseau ROSE). Participants were asked to complete a battery of questionnaires online assessing FCR and other psychological and quality of life variables.

Results: A total of 89 women completed the survey. Most participants had undergone a preventive mastectomy (62.9%) and a preventive salpingo-oophorectomy (75.3%) at the time of the study. The mean Fear of Cancer Recurrence Inventory-severity score was 16.8, which exceeds the clinical cut-off score of 13, and 70.8% of the participants showed a clinical level of FCR. FCR was significantly associated with higher levels of anxiety and depression, and higher avoidance and intolerance of uncertainty, but not with quality of life. No significant difference was observed on the total FCR score between women who had received preventive surgery (mastectomy and/or salpingo-oophorectomy) and those considering it, and those not considering it. The association was significant between higher FRC scores and greater decisional conflicts and regrets about choosing to undergo preventive surgery.

Conclusion: These data suggest that FCR is a significant problem for breast cancer survivors carrying a BRCA1/2 genetic mutation, even after undergoing a prophylactic surgery. This highlights the importance of providing these women with specific psychological intervention focusing on FCR.

背景:对癌症复发的恐惧(FCR)在不同程度上影响着几乎所有接受过癌症治疗的患者。携带 BRCA1 或 BRCA2 基因突变的乳腺癌幸存者是癌症复发的高危人群。目前还没有研究专门对这一人群的 FCR 进行评估:这项横断面研究以接受过乳腺癌治疗且携带 BRCA1/2 基因突变的女性为对象,旨在(目的:这项横断面研究的对象是接受过乳腺癌治疗且携带 BRCA1/2 基因突变的女性,旨在:(1)评估 FCR 的平均水平,并估计临床水平 FCR 患者的比例;(2)研究 FCR 与选定的心理变量(如回避、不耐受不确定性)和生活质量之间的关系;(3)探讨 FCR 水平是否随过去接受的预防性治疗而变化;以及(4)评估 FCR 与在各种预防性选择中是否存在决策冲突或遗憾之间的关联:通过向肿瘤基因网络邮件列表(Réseau ROSE)发送电子邮件的方式招募参与者。参与者需在线完成一系列问卷,评估FCR及其他心理和生活质量变量:共有 89 名妇女完成了调查。大多数参与者在调查时已接受了预防性乳房切除术(62.9%)和预防性输卵管切除术(75.3%)。对癌症复发的恐惧清单-严重程度的平均得分为 16.8 分,超过了 13 分的临床临界值,70.8% 的参与者显示出了 FCR 的临床水平。FCR 与较高程度的焦虑和抑郁、较高程度的回避和对不确定性的不容忍明显相关,但与生活质量无关。接受过预防性手术(乳房切除术和/或输卵管切除术)的妇女、考虑接受手术的妇女和未考虑接受手术的妇女在 FCR 总分上没有明显差异。FCR得分越高,选择接受预防性手术时的决策冲突和后悔程度就越大,两者之间存在明显关联:这些数据表明,对于携带 BRCA1/2 基因突变的乳腺癌幸存者来说,即使接受了预防性手术,FCR 仍是一个重要问题。这凸显了为这些妇女提供以 FCR 为重点的特定心理干预的重要性。
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引用次数: 0
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 Q3 ONCOLOGY 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

Background: 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.

Aim: Identification of the possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients.

Methods: 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.

Results: 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 (F1,2=0.5, p1,2=0.8, F1,3=2.31, p1,3=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 (F1,2=107, p1,2<0.001), Group 3-2.47 ± 0.17 (F1,3=150, p1,3<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 (F1 - 2=200; p1 - 2<0.001), in patients without genetic predisposition to cancer(Group 3), the level of TAA did not change compared to the control (F1 - 3= 2.13; p1 - 3=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.

背景:据估计,遗传性癌症占全球癌症发病率的 10%;据认为,5% 的甲状腺癌是遗传性的。基因中有害突变的遗传与终生罹患癌症的高风险有关。癌症易感基因可通过氧化应激机制加强主要信号通路的激活,从而促进甲状腺癌的发生和发展。目的:确定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的联系:方法:对甲状腺癌患者(有遗传倾向和无遗传倾向)进行调查。研究参与者在有限责任公司(LLC)"肿瘤科学研究中心"(格鲁吉亚,第比利斯)接受治疗。研究小组在 2020 年至 2021 年期间收集数据。研究人员对患者血液中的甲状腺激素含量(游离三碘甲状腺原氨酸(fFT3)、游离甲状腺素(fFT4)、结合三碘甲状腺原氨酸(FT3)、结合甲状腺素(FT4)、促甲状腺激素(TSH))和氧化应激强度(非酶抗氧化系统(TAA)总活性和脂质过氧化产物丙二醛(MDA)含量)进行了调查:甲状腺癌患者(第 2 组和第 3 组)与对照组(第 1 组)血清中游离型和结合型 T3 和 T4 水平的差异无统计学意义(F1,2=0.5,P1,2=0.8;F1,3=2.31,P1,3=0.16)。与对照组(第 1 组)相比,甲状腺癌患者的促甲状腺激素水平明显升高(促甲状腺激素(平均值 ± 标准误差):组 1- 1.21 ± 0.12,组 2-2.45 ± 0.11(F1,2=107,P1,21,3=150,P1,31 - 2=200;P1 - 21 - 3= 2.13;P1 - 3=0.15),结论:氧化应激在甲状腺癌患者中起着至关重要的作用:氧化应激在肿瘤发生过程中起着关键作用,抗氧化剂/氧化剂失衡可能导致正常组织恶性转化。在具有癌症家族易感性的患者中,参与氧化代谢调控的多个基因的突变可能会导致氧化还原平衡的破坏,增加氧化应激水平,并导致甲状腺癌的发生。
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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 Q3 ONCOLOGY 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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

研究背景该研究的目的是测试子宫内膜癌的普遍筛查策略,以评估其根据两个既定临床标准发现林奇综合征(LS)病例的有效性:阿姆斯特丹 II 标准和修订后的贝塞斯达标准,选择病例进行免疫组化(IHC)预检。随后对病例进行 DNA 错配修复(MMR)基因种系致病变异筛查:使用针对 DNA 错配修复蛋白 MLH1、PMS2、MSH2 和 MSH6 的抗体对 221 例子宫内膜癌(EC)病例进行了 IHC 检测。54例患者发现了MMR缺失,其中52例进行了基因突变筛查:结果:在这组患者中,使用阿姆斯特丹II标准发现了2例(0.9%)LS,贝塞斯达标准发现了2例(0.9%),普遍检测发现了5例(2.3%)。将普遍检测和家族史标准结合使用,结果发现了5例(2.3%)LS患者:根据我们的研究结果和迄今为止的其他类似研究,我们提出了EC肿瘤LS的筛查方案,即对所有70岁以前确诊的EC新病例使用IHC对四种MMR蛋白进行预筛查,然后对所有缺失MSH2和/或MSH6或仅缺失PMS2的肿瘤进行突变筛查,并考虑对符合阿姆斯特丹II临床标准的病例进行所有LS基因的突变筛查,无论IHC上的MMR状态如何。
{"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 Q3 ONCOLOGY 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

Background: 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.

Case presentation: 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.

Conclusions: These observations suggest that germline mutations in EGFR T790M could be strongly linked to a familial predisposition to lung cancer.

背景:约50%的非小细胞肺癌会发生表皮生长因子受体基因的体细胞突变,其中T790M突变是导致表皮生长因子受体-TKI药物继发性耐药的重要原因。然而,EGFR T790M 基因突变很少发生:在本研究中,我们报告了一例与表皮生长因子受体(EGFR)T790M 基因突变相关的肺腺癌家族性病例。主要研究对象被诊断为肺腺癌 IV 期,在接受奥希替尼治疗的 19 个月期间疾病未见进展。我们收集了一名肺腺癌患者的临床病理和家族数据。我们对该患者的肿瘤组织进行了 40 个关键基因的新一代测序。为了检测表皮生长因子受体种系突变,对该患者及其两个女儿的外周血单核细胞进行了桑格测序。在原告的肺癌组织中发现了表皮生长因子受体 T790M、表皮生长因子受体 19-Del、TP53 和 PIK3CA 等突变。此外,通过对该患者及其女儿的外周血样本进行测序,确认了他们的种系表皮生长因子受体(EGFR)T790M突变。CT 扫描显示,两个女儿都有多发性肺结节:这些观察结果表明,表皮生长因子受体 T790M 的种系突变可能与肺癌的家族易感性密切相关。
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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 Q3 ONCOLOGY 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
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.
胃腺癌和胃近端息肉病(GAPPS)是一种常染色体显性遗传综合征,以胃底腺息肉(FGP)和胃癌风险增加为特征。该综合征被确认为临床实体还不到十年。临床怀疑可能很复杂,从胃镜检查偶然发现胃底腺息肉到出现消化不良和呕吐的梗阻性症状都有可能。通过基因检测 APC 基因启动子 1B 区的致病变体可确定诊断。到目前为止,还没有确定的临床诊断标准。为了增加对该疾病的了解,并讨论可能的基因检测和监控策略,我们对所有报道的 GAPPS 患者进行了系统性回顾。本综述按照 PRISMA 指南进行组织。检索于 2023 年 9 月 7 日在 MEDLINE 上进行,仅限于人类和英文论文。仅纳入了通过鉴定 APC 启动子 1B 中的致病变异而验证的 GAPPS 患者/家属的研究。共发现 12 篇论文,涉及 113 名患者。在所有情况下,诊断都是通过 APC 启动子 1B 区域内四种不同变体的报告进行基因验证的。88名患者(90.1%)患有胃息肉,其中7名患者患有低度发育不良,5名患者同时患有低度和高度发育不良。37名患者(45.7%)接受了胃切除术。没有十二指肠息肉的报告(0%)。31名患者(30.1%)发现胃癌,中位年龄为48岁(19-75岁不等)。26 名患者死亡(23.2%),其中 19 人罹患胃癌(73.1%)。一名患者被诊断为转移性结直肠癌(2.2%),享年 73 岁。19名患者的结直肠表现为息肉小于20个(41.3%)。APC 启动子 1B 区致病变异患者罹患胃息肉病和早发胃癌的风险增加。然而,该病的临床表现和渗透性差异很大,这使得有关监测和预防性胃切除术时机的决策具有挑战性。
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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 Q3 ONCOLOGY 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

Background: 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.

Case presentation: 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.

Conclusions: 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.

背景:CDKN2A 基因突变会导致家族性非典型多痣黑色素瘤综合征(FAMMM)(OMIM #155,601),该病与胰腺导管腺癌和黑色素瘤风险增加有关。FAMMM 在全球都有报道,但在日本相当罕见。我们报告了两个家族性胰腺癌患者家庭,他们通过全面的基因组分析偶然发现了 CDKN2A 的疑似致病变体:第一个病例是一名 74 岁的女性,诊断为胰腺癌并多发性肝转移。她有胰腺癌家族史,但没有恶性黑色素瘤个人或家族史。全外显子测序检测出一个种系 CDKN2A 变异,经评估可能是致病的。她去世后,她的女儿们得知了这一结果,其中一个女儿体内也检测到了相同的 CDKN2A 变异。女儿被转诊到附近的医院接受临床治疗。第二个病例是一名胰腺导管腺癌患者,65 岁。他有胰腺癌家族史,但没有恶性黑色素瘤个人或家族史。他利用胰腺癌组织进行了全面的基因组分析测试,检测出 CDKN2A 的推测种系致病变体。种系检测证实了相同的 CDKN2A 变异。对其亲属的基因分析结果为阴性。其他血缘亲属计划在未来进行基因分析。我们报告了两个家族性胰腺癌家庭,他们通过全面基因组分析偶然发现了疑似 CDKN2A 致病变体:在当前的日本精准医疗中,综合基因分析可以揭示罕见的遗传综合征,并为我们提供为患者及其亲属提供健康管理的机会。然而,由于日本缺乏 CDKN2A 变异基因携带者的基因和临床数据,在评估变异基因的致病性和对高危器官的监控程度方面,还存在一些特定基因的问题。
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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 Q3 ONCOLOGY 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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

背景:林奇综合征是遗传性结直肠癌和子宫内膜癌最常见的病因。改变生活方式可为辅助预防癌症提供机会。在这项研究中,我们旨在了解林奇综合征患者的可改变风险因素,并将其与国际癌症预防指南进行比较:方法:我们采用调查方法开展了一项横断面研究。在公众和患者的参与下,调查通过患者权益团体和社交媒体进行传播。于 2023 年 4 月收集了自我报告的人口统计和健康行为。调查采用了世界癌症研究基金会(WCRF)的指南,比较了9种生活方式建议(包括饮食、体育锻炼、体重和酒精摄入量)的遵守比例。作为生活方式风险的替代指标,计算并比较了各组的坚持率中位数:结果:来自 13 个国家的 156 名林奇综合征患者参与了研究。中位年龄为 51 岁,54% 为癌症幸存者。平均体重指数为 26.7,每周中等强度至剧烈运动的平均持续时间为 90 分钟。每周乙醇摄入量的中位数为 60 克,3% 的人表示目前正在吸烟。世界癌症研究基金会提出的癌症预防建议的采纳率从 9% 到 73% 不等,除一项建议外,其他建议均有结论:我们描述了林奇综合征患者的可改变风险特征,并根据普通人群的生活方式指南概述了干预目标。随着支持林奇综合征可改变因素相关性的证据的出现,行为改变可能会被证明是一种有效的癌症预防手段。
{"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 Q3 ONCOLOGY Pub Date : 2024-06-12 DOI: 10.1186/s13053-024-00281-9
Annmarie Taheny, Haylie McSwaney, Julia Meade

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.

美国国家综合癌症网络(National Comprehensive Cancer Network ®,NCCN ®)目前的结直肠遗传/家族高风险评估指南为已确诊遗传性癌症患者的基因检测提供了有限的指导。我们将介绍一位 36 岁女性的病例,她在 23 岁时接受了 MLH1 基因家族变异(c.283del)的基因检测,之后被诊断为林奇综合征。在进行家族变异检测时,患者曾患有霍奇金淋巴瘤,后来在 33 岁时罹患 IIIa 期盲肠腺癌,35 岁时罹患转移性甲状腺乳头状癌。患者的家族史包括 39 岁时被诊断出患有结直肠癌的一级亲属,患有结直肠癌、子宫内膜癌和胃癌的多个二级亲属,以及患有乳腺癌的三级和四级亲属。鉴于她的个人和家族病史,医生建议她进行一次全面的癌症检查。这项检查发现了第二种遗传性癌症易感综合征:CHEK2 基因中的一个可能致病的变体(c. 349 A > G)。最近有报告称,CHEK2 基因的这一特定变异会中度增加罹患乳腺癌的风险。第二种癌症易感综合征的发现对患者的筛查和风险管理具有重要意义。虽然不常见,但在评估遗传性癌症患者和家庭时,即使已经发现了一个家族性变异,也要考虑到个人有多种癌症易感综合征的可能性。
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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 Q3 ONCOLOGY 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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

背景:导致胃癌的粘液序列变化和家族性肠型胃癌病例的发生与幽门螺杆菌感染有广泛联系。在这项研究中,我们分析了幽门螺杆菌感染者肠道中涉及癌症发生和炎症过程的基因变异。我们的目的是检测这些基因的突变是否会导致胃癌的发生,以及是否有遗传因素使幽门螺杆菌感染更有可能导致胃癌。由于幽门螺杆菌感染比较常见,发现这种遗传倾向可用于建立风险群体和制定治疗计划:我们的研究涵盖了对癌症发生相关基因变异的分析:方法:我们的研究涵盖了与癌症发生有关的基因变异分析:TP53(rs11540652、rs587782329、COSM10771)、MSH2(rs193922376)、MLH1(rs63750217),以及肠道炎症过程:结果发现,幽门螺杆菌感染患者的NOD2(rs2066847、rs2066842)、IL1A(rs1800587)和IL1B(rs1143634)基因突变更常见:与慢性胃炎、慢性萎缩性胃炎、肠化生、发育不良或胃癌患者相比,肠型胃癌和家族性胃癌患者中的突变更为常见(p值=0.00824),家族性胃癌患者与其他粘膜病变患者相比,p53突变的发生率更高(p值=0.000049)。此外,胃癌患者的 NOD2 基因 rs2066842 变体的基因型主要为 TT 或 CT:结论:参与炎症过程的其他白细胞介素基因未发生有统计学意义的变化,这可能表明幽门螺杆菌感染是胃黏膜炎症过程发展的潜在诱因,并通过微生物群失调导致肠胃癌的发生。所分析基因的突变与更严重的粘膜变化相关,TP53 基因突变更为常见,而其他基因突变在胃癌家族史中出现的频率有限。
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引用次数: 0
期刊
Hereditary Cancer in Clinical Practice
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