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Progression of duodenal neoplasia to advanced adenoma in patients with familial adenomatous polyposis. 家族性腺瘤性息肉病患者的十二指肠肿瘤进展到晚期腺瘤。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-27 DOI: 10.1186/s13053-023-00264-2
Hiroko Nakahira, Yoji Takeuchi, Yusaku Shimamoto, Shingo Ishiguro, Hiroshi Yunokizaki, Yasumasa Ezoe, Fumie Fujisawa, Ryu Ishihara, Tetsuji Takayama, Teruhiko Yoshida, Michihiro Mutoh, Hideki Ishikawa

Background: Patients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP.

Methods: Of 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV.

Results: During the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3' side mutation in their adenomatous polyposis coli gene.

Conclusions: NADAs in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.

背景:家族性腺瘤性息肉病(familial adenomatous polyposis, FAP)患者一生中发生十二指肠腺瘤的风险接近100%,与一般人群相比,其发生十二指肠癌的相对风险较高。我们进行了一项回顾性研究,探讨FAP患者非壶腹十二指肠腺瘤(NADAs)的进展和晚期病变的危险因素。方法:在2个研究所的248例139个家系患者中,我们评估了151例100个家系的大肠腺瘤性息肉病基因致病种系变异患者,不包括马赛克变异。我们评估了FAP患者中NADAs的患病率,这些腺瘤在观察期间向晚期腺瘤的进展情况,以及终生发展为高级别不典型增生(HGD)、大(≥10 mm)十二指肠腺瘤和Spiegelman iv期的危险因素。在中位7年的观察期内,NADAs、息肉≥20个、息肉≥10 mm、HGD和末次食管胃十二指肠镜检查ⅳ期患者的发生率分别增加了1.6倍、1.7倍、5倍、22倍和9倍。3例(2%)患者发生了粘膜内癌,但由于我们对晚期腺瘤进行了内镜干预,在观察期间没有患者发生浸润性癌。113例患者中有71%出现分期进展。IV期更常见于女性、结肠切除术史患者和腺瘤性大肠息肉病基因3′侧突变患者。结论:FAP患者的nada经常加重。我们的研究结果提示,发生十二指肠腺瘤的FAP患者应进行调查,以防止发生十二指肠癌。
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引用次数: 0
"Go ahead and screen" - advice to healthcare systems for routine lynch syndrome screening from interviews with newly diagnosed colorectal cancer patients. “继续进行筛查”-对新诊断的结直肠癌患者进行常规lynch综合征筛查的医疗保健系统的建议。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-17 DOI: 10.1186/s13053-023-00270-4
Jennifer L Schneider, Alison J Firemark, Sara Gille, James Davis, Pamala A Pawloski, Su-Ying Liang, Mara M Epstein, Jan Lowery, Christine Y Lu, Ravi N Sharaf, Andrea N Burnett-Hartman, Victoria Schlieder, Zachary M Salvati, Deborah Cragun, Alanna Kulchak Rahm, Jessica Ezzell Hunter

Background: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities.

Methods: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives.

Conclusion: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes.

Trial registration: Not available: not a clinical trial.

背景:Lynch综合征(LS)是遗传性结直肠癌(CRC)最常见的病因。建议对新诊断的CRC病例进行普遍肿瘤筛查(UTS),以帮助诊断LS并降低癌症相关的发病率和死亡率。然而,并非所有卫生系统都采用了UTS流程,由于系统和患者层面的复杂性,实施可能不一致。方法:为了从患者的角度确定障碍、促进因素和改进UTS过程的建议,我们对最近诊断为CRC但未筛查或未意识到LS的患者进行了深入的半结构化访谈。患者从美国8个不同地区的卫生系统中招募。访谈以电话方式进行,时长60分钟,录音并抄写。采用归纳的、恒定的比较分析方法。结果:我们在8个系统中完成了75次访谈。大多数参与者是白人(79%),大约一半(52%)是男性,平均年龄为60岁。大多数自我报告没有(60%)或很少(40%)事先意识到LS。总体而言,96%的患者表示UTS应成为结直肠癌肿瘤的常规护理标准,并一直引用四个主要动机来了解他们的LS状态并参与LS识别过程:“知识就是力量”;“家庭知识”;“预防和发现”;以及“治疗和监视”。与筛查和识别LS过程有关的常见问题包括:为患者带来预期的担忧,潜在的成本和基因测试的准确性,以及可能因LS诊断而影响个人的健康保险范围。患者建议卫生系统亲自或通过训练有素的LS专家电话通报LS结果;提供主动的口头和书面教育,关于LS的筛查步骤,以及任何后续监测建议;并支持患者与任何血亲沟通他们的LS筛查。结论:我们的定性研究结果表明,CRC患者强烈希望医疗保健系统定期实施和提供UTS。患者为卫生系统提供了关键的见解,以指导未来实施和优化UTS和其他LS筛查项目,最大限度地诊断LS患者,改善癌症相关的监测和结果。试验注册:Not available:不是临床试验。
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引用次数: 0
Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience. 日本brca2阳性非侵袭性乳腺癌同时双侧乳房切除术和RRSO: 1例报告和初步经验分析
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-13 DOI: 10.1186/s13053-023-00268-y
Aya Tanaka, Megumi Matsumoto, Mami Takao, Shoko Miura, Yuri Hasegawa, Ryota Otsubo, Hiroko Hayashi, Ichiro Isomoto, Kiyonori Miura, Takeshi Nagayasu

Background: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer.

Case presentation: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment.

Conclusions: We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

背景:在日本,自2020年4月以来,遗传性乳腺癌和卵巢癌(HBOC)综合征的基因检测、监测和降低风险的手术已被纳入日本国民保险体系。另一方面,目前的情况是,即使是HBOC患者,医疗保健,包括对未确诊(无癌症)患者的监测,也是自费的。我们报告了一个病例,在无癌HBOC监测期间,患者自费在早期诊断出乳腺癌,并在乳腺癌治疗的同时进行了降低风险的手术。病例介绍:患者为63岁女性。她的妹妹在30多岁时有乳腺癌病史,通过基因检测发现是BRCA2致病变异携带者。因此,患者来到我院遗传科进行基因检测(自费)。在同一位点发现了一种致病变异。在患者自费的年度乳腺和卵巢监测中,一位在乳腺磁共振造影(MRI)方面有足够专业知识的医生注意到乳房MRI造影增强模式的变化,并进行了穿刺活检,发现导管原位癌。在患者的要求下,除乳腺癌治疗外,她同时接受了对侧降低风险的乳房切除术和降低风险的输卵管卵巢切除术。结论:我们遇到了一个病例,在癌症治疗和降低风险的手术同时进行致病变异携带者,他非常担心患癌症。对无癌BRCA1/2突变携带者的监测和扩大手术保险范围是未来重要的问题。
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引用次数: 0
Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan. 巴基斯坦一个未选择的胰腺癌患者队列中BRCA1和BRCA2种系变异的患病率
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-11 DOI: 10.1186/s13053-023-00269-x
Noor Muhammad, Ayesha Azeem, Shumaila Arif, Humaira Naeemi, Iqra Masood, Usman Hassan, Bushra Ijaz, Faisal Hanif, Aamir Ali Syed, Muhammed Aasim Yusuf, Muhammad Usman Rashid

Background: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.

Methods: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls.

Results: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers.

Conclusions: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.

背景:BRCA1和BRCA2 (BRCA1/2)是白种人胰腺癌患者中最常研究的基因,而亚洲人的报道有限。我们的目的是调查BRCA1/2种系变异在巴基斯坦胰腺癌患者中的患病率。方法:采用变性高效液相色谱和高分辨率熔解分析对150例未入选和前瞻性入选的胰腺癌患者进行BRCA1/2种系变异的全面筛选,然后对变异片段进行DNA测序。利用计算机工具分析了这些新变异的致病作用。在200名无癌对照中进一步筛选了潜在的功能性变异。结果:仅在BRCA2中检测到蛋白截断变异,患病率为0.7%(1/150)。在一名有腹部癌症家族史的71岁帕坦族男性患者中发现移码BRCA2变异(p.Asp946Ilefs*14)。此外,我们在BRCA2中发现了一个新的变异(p.Glu2650Gln),在BRCA1中发现了两个先前报道的变异(p.g thr293ser)和BRCA2中发现了两个变异(p.g ile2296leu),在BRCA2中发现了一个复发的无义变异(p.g lys3326ter)。这些变异被归类为不确定意义变异(VUS)。值得注意的是,这些VUS携带者都没有胰腺癌或其他癌症的家族史。结论:在第一项研究中,BRCA1/2致病性变异在巴基斯坦胰腺癌患者中发现频率较低。建议在巴基斯坦胰腺癌患者中进行全面的多基因面板检测,以加强对该人群的遗传理解。
{"title":"Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan.","authors":"Noor Muhammad, Ayesha Azeem, Shumaila Arif, Humaira Naeemi, Iqra Masood, Usman Hassan, Bushra Ijaz, Faisal Hanif, Aamir Ali Syed, Muhammed Aasim Yusuf, Muhammad Usman Rashid","doi":"10.1186/s13053-023-00269-x","DOIUrl":"https://doi.org/10.1186/s13053-023-00269-x","url":null,"abstract":"<p><strong>Background: </strong>BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.</p><p><strong>Methods: </strong>One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls.</p><p><strong>Results: </strong>Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers.</p><p><strong>Conclusions: </strong>In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"22"},"PeriodicalIF":1.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720683","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
Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria. 缺乏Amsterdam II或Bethesda标准的林奇综合征患者的诊断。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-10-20 DOI: 10.1186/s13053-023-00266-0
Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Melva Gutiérrez-Angulo, Anahí González-Mercado, José Miguel Moreno-Ortiz

Background: Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history.

Main body: Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis.

Conclusion: Universal screening could be an option to address the problem of underdiagnosis.

背景:林奇综合征(Lynch Syndrome,LS)是一种常染色体显性遗传疾病,其特征是由于错配修复系统基因的致病性变异而导致的癌症遗传易感性。根据家族史,通过实施阿姆斯特丹II和修订后的贝塞斯达标准来发现病例。主体:符合标准的患者接受后验,如种系DNA测序,以确认诊断。然而,这些标准的敏感性较差,因为超过四分之一的LS患者不符合标准。标准缺乏敏感性很可能是由于该综合征的外显率不完全所致。发生特定类型癌症的外显率和风险高度依赖于受影响的基因和可能的变体。低渗透基因变异的患者患与LS相关的癌症的风险较低,导致家庭的几代人未受影响,显示出较少的明确模式。本研究的重点是描述LS病例的遗传方面,这些遗传方面是用于诊断LS的临床标准缺乏敏感性的原因。结论:普遍筛查可能是解决诊断不足问题的一种选择。
{"title":"Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria.","authors":"Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Melva Gutiérrez-Angulo, Anahí González-Mercado, José Miguel Moreno-Ortiz","doi":"10.1186/s13053-023-00266-0","DOIUrl":"10.1186/s13053-023-00266-0","url":null,"abstract":"<p><strong>Background: </strong>Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history.</p><p><strong>Main body: </strong>Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis.</p><p><strong>Conclusion: </strong>Universal screening could be an option to address the problem of underdiagnosis.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"21"},"PeriodicalIF":1.7,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685252","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 prevalence of lynch syndrome (DNA mismatch repair protein deficiency) in patients with primary localized prostate cancer using immunohistochemistry screening. 应用免疫组化筛查原发性局限性前列腺癌症患者的林奇综合征(DNA错配修复蛋白缺乏)的患病率。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-10-12 DOI: 10.1186/s13053-023-00265-1
Suguru Oka, Shinji Urakami, Kiichi Hagiwara, Michikata Hayashida, Kazushige Sakaguchi, Yuji Miura, Naoko Inoshita, Masami Arai

Background: Prostate cancer is one of the most heritable human cancers. Lynch syndrome is an autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes, which are also associated with an increased incidence of prostate cancer. However, prostate cancer has not been defined as a Lynch syndrome-associated cancer. The proportion of Lynch syndrome patients in primary prostate cancers is unclear. In this study, we investigated MMR protein loss using universal immunohistochemical screening to determine the prevalence of Lynch syndrome in patients with localized prostate cancer who underwent radical prostatectomy.

Methods: One hundred twenty-nine surgical specimens from radical prostatectomy performed at Toranomon Hospital between 2012 and 2015 were retrospectively tested using universal screening with immunohistochemistry staining for expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. For all suspected MMR-deficient patients, germline genetic tests focusing on MMR genes were performed.

Results: MMR protein loss was found in only one patient (0.8%) who showed dual MSH2/MSH6 loss. This patient showed a single nucleotide pathogenic germline mutation from c.1129 C to T (p.Gln377*) at exon 7 in the MSH2 gene. He was diagnosed with a primary prostate cancer at 66 years of age. He had a documented history of Lynch syndrome (Muir-Torre syndrome) with previous colon cancer, sebaceous tumor, and keratoacanthoma as well as subsequent bladder cancer, all of which also showed dual MSH2/MSH6 loss. He also had a strong family history of colorectal and other Lynch syndrome-associated cancers. The pathological stage was pT3aN0M0, and the pathological grade was Gleason 7(4 + 3) with tertiary pattern 5.

Conclusions: In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

背景:癌症是人类最易遗传的癌症之一。林奇综合征是一种由DNA错配修复(MMR)基因种系突变引起的常染色体显性遗传,也与癌症发病率增加有关。然而,前列腺癌症尚未被定义为林奇综合征相关的癌症。林奇综合征患者在原发性前列腺癌中的比例尚不清楚。在这项研究中,我们使用通用免疫组织化学筛查来研究MMR蛋白损失,以确定接受根治性前列腺切除术的局限性前列腺癌症患者林奇综合征的患病率。方法:使用免疫组织化学染色的通用筛查方法,对2012年至2015年间在Toranomon医院进行的129例根治性前列腺切除术的手术标本进行MMR蛋白MLH1、PMS2、MSH2和MSH6表达的回顾性检测。对于所有疑似MMR缺乏的患者,进行了以MMR基因为重点的种系遗传测试。结果:只有一名患者(0.8%)出现MSH2/MSH6双重缺失,MMR蛋白缺失。该患者在MSH2基因的外显子7处表现出从c.1129C到T(p.Gln377*)的单核苷酸致病性种系突变。他在66岁时被诊断为原发性前列腺癌癌症。他有林奇综合征(Muir-Torre综合征)病史,既往结肠癌癌症、皮脂腺肿瘤、角质棘皮瘤以及随后的癌症,所有这些都显示MSH2/MSH6双重缺失。他还有结直肠癌和其他林奇综合征相关癌症的家族史。病理分期为pT3aN0M0,病理分级为Gleason 7级(4 + 3) 结论:本研究对一系列前列腺癌症患者进行了林奇综合征MMR蛋白的免疫组化筛查。林奇综合征在局限性前列腺癌症中的患病率为0.8%,与其他林奇综合症相关癌症相比,这是较低的。
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引用次数: 0
Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement. 显性遗传微小卫星不稳定癌症-林奇综合征-EHTG,PLSD位置说明。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-10-11 DOI: 10.1186/s13053-023-00263-3
Pal Møller, Toni T Seppälä, Aysel Ahadova, Emma J Crosbie, Elke Holinski-Feder, Rodney Scott, Saskia Haupt, Gabriela Möslein, Ingrid Winship, Sanne W Bajwa-Ten Broeke, Kelly E Kohut, Neil Ryan, Peter Bauerfeind, Laura E Thomas, D Gareth Evans, Stefan Aretz, Rolf H Sijmons, Elizabeth Half, Karl Heinimann, Karoline Horisberger, Kevin Monahan, Christoph Engel, Giulia Martina Cavestro, Robert Fruscio, Naim Abu-Freha, Levi Zohar, Luigi Laghi, Lucio Bertario, Bernardo Bonanni, Maria Grazia Tibiletti, Leonardo S Lino-Silva, Carlos Vaccaro, Adriana Della Valle, Benedito Mauro Rossi, Leandro Apolinário da Silva, Ivana Lucia de Oliveira Nascimento, Norma Teresa Rossi, Tadeusz Dębniak, Jukka-Pekka Mecklin, Inge Bernstein, Annika Lindblom, Lone Sunde, Sigve Nakken, Vincent Heuveline, John Burn, Eivind Hovig, Matthias Kloor, Julian R Sampson, Mev Dominguez-Valentin

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

对由四个错配修复(MMR)基因之一MSH2、MLH1、MSH6和PMS2的致病性变体引起的显性遗传微卫星不稳定(MSI)癌症的识别改变了我们对致癌作用的理解。这些MMR基因的遗传性功能缺失变异导致四种显性遗传癌症综合征,具有不同的外显率和表达率:四种林奇综合征。没有人具有“平均性别”或“平均林奇综合征基因”的致病性变体,不按基因和性别分层的结果对任何人都无效。癌发生可能是从细胞分裂增加到癌症局部转移的线性过程。此外,在林奇综合征(LS)中,我们现在认识到两个随机过程之间的动态平衡:MSI产生的异常细胞和宿主的适应性免疫系统清除它们的能力。后者可以解释为什么结肠镜检查监测不能降低LS中结直肠癌癌症的发病率,但可以改善预后。LS中大多数早发结肠癌、子宫内膜癌和卵巢癌现已治愈,大多数与癌症相关的死亡发生在其他器官的后续癌症之后。阿司匹林降低了LS中结直肠癌和其他癌症的发病率。免疫治疗增加了宿主免疫系统摧毁MSI癌症的能力。结肠镜监测、阿司匹林预防和免疫疗法是个性化精准医学预防和治疗遗传性MSI癌症的重要进步。
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引用次数: 0
Periampullary tumors in a patient with pancreatic divisum and neurofibromatosis type 1: a case report. 1型胰腺分裂和神经纤维瘤病患者的壶腹周围肿瘤:一例报告。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-09-29 DOI: 10.1186/s13053-023-00262-4
Bin-Bin Li, Hui Zheng, Yi-Dan Lou, Wen-Wei Zhang, Song Zheng

Introduction: We present a case of a male patient with neurofibromatosis type 1 diagnosed with pancreatic divisum and several gastrointestinal tumors. A 55-year-old man was admitted to the hospital with recurrent chronic pancreatitis, indicating a large mass in the ampulla. In addition, genetic testing revealed two unique germline mutations in the neurofibromin (NF1) gene, and their potential interaction in promoting cancer was further investigated.

Conclusion: The first similar case was reported in 2020. The current case was distinct from other cases since an additional two NF1 mutations were found in the patient. In conjunction with prior case reports, our findings imply that genetic testing in patients diagnosed with neurofibromatosis type 1 could be helpful in the development of effective treatments.

引言:我们报告一例男性1型神经纤维瘤病患者,诊断为胰腺分裂和几种胃肠道肿瘤。一名55岁的男子因复发性慢性胰腺炎入院,表明壶腹有一个大肿块。此外,基因检测揭示了神经纤维蛋白(NF1)基因中两种独特的种系突变,并进一步研究了它们在促进癌症方面的潜在相互作用。结论:2020年报告了首例类似病例。目前的病例与其他病例不同,因为在患者中发现了另外两个NF1突变。结合先前的病例报告,我们的研究结果表明,对诊断为1型神经纤维瘤病的患者进行基因检测可能有助于开发有效的治疗方法。
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引用次数: 0
Familial pancreatic cancer: a case study and review of the psychosocial effects of diagnoses on families. 家族性胰腺癌:诊断对家庭的心理社会影响的个案研究和回顾。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-09-08 DOI: 10.1186/s13053-023-00261-5
Tracy Lowe, Jane DeLuca, Ludovico Abenavoli, Luigi Boccuto

Background: Familial pancreatic cancer touches families through a genetic susceptibility to developing this neoplasia. Genetic susceptibility is assessed via family history, genetic testing, or both. Individuals with two or more first-degree relatives or three or more relatives of any degree diagnosed with pancreatic cancer are considered at elevated risk. Following a diagnosis of familial pancreatic cancer, patients and families face uncertainty and anxiety about the future. Psychosocial effects of a pancreatic cancer diagnosis on families include fear, concerns about personal health, and how lifestyle may impact the risk of developing pancreatic cancer.

Case presentation: A 66-year-old male was diagnosed with pancreatic ductal adenocarcinoma stage IIB, T3, N1, M0. A genetic referral was made due to a history of multiple cases of pancreatic cancer within the patient's family. Genetic testing revealed the patient had a pathogenic variant in the ATM gene that is associated with an increased risk for pancreatic cancer development. The patient's one adult child was offered testing due to the autosomal dominant pattern of inheritance for this variant. The adult child was found to have the same pathogenic variant. She expressed fear for her future and her child's future health and longevity. Discussing a case study allows us to capture the multi-faceted relationship between the disease, the affected individuals, and their families. Examining the psychosocial stresses and concerns when there is a pancreatic cancer diagnosis in the family is essential to provide holistic care to patients and families.

Conclusions: The psychosocial effects of FPC may be overwhelming for patients and families. Healthcare providers can offer education, support, and referrals to appropriate services to help families cope through stages of evaluation, diagnosis, and treatment of FPC.

背景:家族性胰腺癌通过发生这种肿瘤的遗传易感性接触家族。遗传易感性通过家族史、基因检测或两者同时评估。有两个或两个以上一级亲属或三个或三个以上亲属被诊断患有胰腺癌的人被认为是高危人群。在被诊断为家族性胰腺癌后,患者及其家人面临着对未来的不确定性和焦虑。胰腺癌诊断对家庭的心理社会影响包括恐惧、对个人健康的担忧以及生活方式如何影响患胰腺癌的风险。病例介绍:66岁男性,诊断为胰管腺癌IIB, T3, N1, M0期。由于患者家族中有多例胰腺癌的病史,因此进行了遗传转诊。基因检测显示,患者的ATM基因有致病变异,这与胰腺癌发展的风险增加有关。由于该变异的常染色体显性遗传模式,患者的一个成年子女接受了检测。发现成年儿童具有相同的致病变异。她表达了对自己和孩子未来健康和长寿的担忧。讨论一个案例研究可以让我们捕捉到疾病、受影响的个人和他们的家庭之间的多方面关系。当家庭中有胰腺癌诊断时,检查心理社会压力和担忧对于向患者和家庭提供全面护理至关重要。结论:FPC对患者和家属的心理社会影响可能是压倒性的。医疗保健提供者可以提供教育、支持和转介到适当的服务,以帮助家庭应对FPC的评估、诊断和治疗阶段。
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引用次数: 0
A novel pathogenic frameshift variant in AXIN2 in a man with polyposis and hypodontia. 一种新的致病移码变异的AXIN2在男子息肉病和下颌畸形。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-08-25 DOI: 10.1186/s13053-023-00260-6
M F Broekema, E J W Redeker, M T Uiterwaal, L P van Hest

Background: WNT signaling is pivotal in embryogenesis and tissue homeostasis. Aberrant WNT signaling, due to mutations in components of this pathway, contributes to the development and progression of human cancers, including colorectal cancer. AXIN2, encoded by the AXIN2 gene, is a key negative regulator and target of the canonical WNT signaling pathway. Germline mutations in AXIN2 are associated with absence of permanent teeth (hypo- and oligodontia) and predisposition to gastrointestinal polyps and cancer. The limited number of patients makes an accurate genotype-phenotype analysis currently challenging.

Case presentation: We present the case of a 55-year-old male with colorectal polyposis and hypodontia. Genetic testing confirmed a novel frameshift germline mutation in exon 8 of the AXIN2 gene. In addition, we provide an updated overview of germline AXIN2 mutations reported in literature.

Conclusions: Although the number of missing teeth is less severe in our patient than in some previously reported cases, our findings provide additional evidence that missing teeth and gastrointestinal neoplasia are associated with rare pathogenic AXIN2 germline mutations.

背景:WNT信号在胚胎发生和组织稳态中起关键作用。异常的WNT信号,由于该通路组分的突变,有助于人类癌症的发生和进展,包括结直肠癌。AXIN2由AXIN2基因编码,是典型WNT信号通路的关键负调控因子和靶点。AXIN2的种系突变与恒牙缺失(缺牙和少牙)以及胃肠道息肉和癌症的易感性有关。数量有限的患者使得准确的基因型-表型分析目前具有挑战性。病例介绍:我们报告一个55岁男性结直肠息肉病和下颌畸形的病例。基因检测证实在AXIN2基因的外显子8上有一个新的移码种系突变。此外,我们提供了文献报道的生殖系AXIN2突变的最新概述。结论:虽然我们的患者缺牙的数量没有以前报道的病例严重,但我们的研究结果提供了额外的证据,证明缺牙和胃肠道肿瘤与罕见的致病性AXIN2种系突变有关。
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引用次数: 0
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Hereditary Cancer in Clinical Practice
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