首页 > 最新文献

Hereditary Cancer in Clinical Practice最新文献

英文 中文
COVID-19 vaccination uptake and safety profile among germline BRCA1 and BRCA2 pathogenic variant carriers in Singapore. 新加坡种系BRCA1和BRCA2致病变异携带者的COVID-19疫苗接种情况和安全性
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-04-12 DOI: 10.1186/s13053-023-00248-2
Zewen Zhang, Nur Diana Binte Ishak, Frances Victoria Fajardo Que, Zi Yang Chua, Sock Hoai Chan, Jianbang Chiang, Joanne Ngeow Yuen Yie

Background: Although Singapore is one of the highest vaccinated countries in the world, vaccine hesitancy remains in a subpopulation, including individuals with cancer predisposition syndromes. At the Cancer Genetics Service National Cancer Centre Singapore, we see patients with germline genetic alterations, most being BRCA1/2 pathogenic/likely pathogenic variant (PV/LPV) carriers. While reported safe for cancer patients, there are limited studies addressing the safety profile and outcomes of COVID-19 vaccination among individuals with germline PV/LPV in cancer predisposition genes such as BRCA1/2. This study aims to evaluate the outcomes of COVID-19 vaccination among germline PV/LPV carriers in BRCA1/2.

Methods: We conducted a phone call survey of COVID-19 vaccination uptake and toxicity in a prospective cohort of 189 participants with germline BRCA1/2 PV/LPV between 1st Sept 2021 and 30th Sept 2021. We collected demographics data including gender, race, age, history of cancer, types of cancer, and number of cancers. Statistical difference in baseline demographics between responders with history of cancer and those without were assessed using Chi-square, Fisher's exact and independent t-test analysis. Logistic regression was used to evaluate effect of demographics on the occurrence of post-vaccination side effects.

Results: Among 189 BRCA1/2 PV/LPV carriers responded, 97 carried PV/LPV in BRCA1 and 92 in BRCA2. Majority were vaccinated (89.5%) and had completed the two-dose vaccine schedule, with 7 (4.1%) received only one dose. The most common post-vaccination side effects was myalgia (56.5%) followed by fever (40.2%), headache (16.3%) and fatigue (11.2%). There were no major severe side events. Evaluation by logistic regression showed that the occurrence of side effects was not affected by PV/LPV gene (BRCA1 or BRCA2), gender, race, age or history of cancer.

Conclusion: The post-vaccination side effects profile among individuals with germline PV/LPV in BRCA1/2 is consistent with the Singaporean general population, hence recommendations for COVID-19 vaccination for these individuals should not differ from non-carriers and should be encouraged by their healthcare providers.

背景:虽然新加坡是世界上疫苗接种率最高的国家之一,但在一个亚人群中,包括有癌症易感综合征的个体,仍然存在疫苗犹豫。在新加坡国家癌症中心癌症遗传服务中心,我们看到有生殖系遗传改变的患者,大多数是BRCA1/2致病性/可能致病性变异(PV/LPV)携带者。虽然有报道称对癌症患者是安全的,但在BRCA1/2等癌症易感基因中携带种系PV/LPV的个体中,关于COVID-19疫苗接种的安全性和结果的研究有限。本研究旨在评估BRCA1/2种系PV/LPV携带者接种COVID-19疫苗的结果。方法:我们在2021年9月1日至2021年9月30日期间,对189名生殖系BRCA1/2 PV/LPV患者进行了COVID-19疫苗接种摄取和毒性的电话调查。我们收集了人口统计数据,包括性别、种族、年龄、癌症病史、癌症类型和癌症数量。有癌症病史和没有癌症病史的应答者的基线人口统计学差异使用卡方、Fisher精确和独立t检验分析进行评估。采用Logistic回归评价人口统计学因素对疫苗接种后副反应发生的影响。结果:189名BRCA1/2 PV/LPV携带者中,97名BRCA1携带者和92名BRCA2携带者携带PV/LPV。大多数(89.5%)接种了两剂疫苗,7人(4.1%)只接种了一剂疫苗。接种疫苗后最常见的副作用是肌痛(56.5%),其次是发热(40.2%)、头痛(16.3%)和疲劳(11.2%)。没有严重的副反应。经logistic回归评估,副作用的发生与PV/LPV基因(BRCA1或BRCA2)、性别、种族、年龄或癌症史无关。结论:BRCA1/2种系PV/LPV个体的疫苗接种后副作用与新加坡普通人群一致,因此对这些个体的COVID-19疫苗接种建议不应与非携带者不同,应得到其医疗保健提供者的鼓励。
{"title":"COVID-19 vaccination uptake and safety profile among germline BRCA1 and BRCA2 pathogenic variant carriers in Singapore.","authors":"Zewen Zhang,&nbsp;Nur Diana Binte Ishak,&nbsp;Frances Victoria Fajardo Que,&nbsp;Zi Yang Chua,&nbsp;Sock Hoai Chan,&nbsp;Jianbang Chiang,&nbsp;Joanne Ngeow Yuen Yie","doi":"10.1186/s13053-023-00248-2","DOIUrl":"https://doi.org/10.1186/s13053-023-00248-2","url":null,"abstract":"<p><strong>Background: </strong>Although Singapore is one of the highest vaccinated countries in the world, vaccine hesitancy remains in a subpopulation, including individuals with cancer predisposition syndromes. At the Cancer Genetics Service National Cancer Centre Singapore, we see patients with germline genetic alterations, most being BRCA1/2 pathogenic/likely pathogenic variant (PV/LPV) carriers. While reported safe for cancer patients, there are limited studies addressing the safety profile and outcomes of COVID-19 vaccination among individuals with germline PV/LPV in cancer predisposition genes such as BRCA1/2. This study aims to evaluate the outcomes of COVID-19 vaccination among germline PV/LPV carriers in BRCA1/2.</p><p><strong>Methods: </strong>We conducted a phone call survey of COVID-19 vaccination uptake and toxicity in a prospective cohort of 189 participants with germline BRCA1/2 PV/LPV between 1st Sept 2021 and 30th Sept 2021. We collected demographics data including gender, race, age, history of cancer, types of cancer, and number of cancers. Statistical difference in baseline demographics between responders with history of cancer and those without were assessed using Chi-square, Fisher's exact and independent t-test analysis. Logistic regression was used to evaluate effect of demographics on the occurrence of post-vaccination side effects.</p><p><strong>Results: </strong>Among 189 BRCA1/2 PV/LPV carriers responded, 97 carried PV/LPV in BRCA1 and 92 in BRCA2. Majority were vaccinated (89.5%) and had completed the two-dose vaccine schedule, with 7 (4.1%) received only one dose. The most common post-vaccination side effects was myalgia (56.5%) followed by fever (40.2%), headache (16.3%) and fatigue (11.2%). There were no major severe side events. Evaluation by logistic regression showed that the occurrence of side effects was not affected by PV/LPV gene (BRCA1 or BRCA2), gender, race, age or history of cancer.</p><p><strong>Conclusion: </strong>The post-vaccination side effects profile among individuals with germline PV/LPV in BRCA1/2 is consistent with the Singaporean general population, hence recommendations for COVID-19 vaccination for these individuals should not differ from non-carriers and should be encouraged by their healthcare providers.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"5"},"PeriodicalIF":1.7,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9306045","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
Pathological complete response to neoadjuvant chemotherapy in triple negative breast cancer - single hospital experience. 三阴性乳腺癌新辅助化疗的病理完全缓解-单一医院经验。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-03-16 DOI: 10.1186/s13053-023-00249-1
Elina Sivina, Lubova Blumberga, Gunta Purkalne, Arvids Irmejs

Background: Triple-negative breast cancer is a heterogeneous molecular subtype of BC. Pathological complete response (pCR) is an important surrogate marker for recurrence-free and overall survival.

Aim of study: The aim of this study was to evaluate clinical and pathological factors that are associated with complete pathological response status in triple-negative breast cancer patients receiving neoadjuvant chemotherapy.

Materials and methods: Eighty triple-negative breast cancer patients who underwent neoadjuvant chemotherapy followed by surgery at Pauls Stradins Clinical University Hospital between January 2018 and January 2020 were retrospectively analysed. Twenty-six patients (32.5%) were BRCA1/2 pathogenic variant carriers.

Results: A total of 32.5% (n = 26) of patients in all study groups and 57.7% (n = 15) of patients with BRCA1/2 pathogenic variants achieved pCR. Forty-seven patients received platinum-based neoadjuvant chemotherapy, and 19 patients (40.4%) achieved complete pathological response. Patients in the pCR group presented with significantly higher Ki-67 scores (p = 0.007), BRCA1/2 pathogenic variants (p = 0.001) and younger age (p = 0.02) than those in the non-pCR group. pCR did not significantly impact recurrence-free survival (RFS) or overall survival (OS). Multivariate analysis revealed that pretreatment N stage (clinical nodal status) was an independent prognostic factor for RFS and OS.

Conclusions: BRCA1 pathogenic variants, high Ki67 score and young age were predictors of pathological complete response, while clinical nodal status predicted survival outcomes in triple-negative breast cancer.

背景:三阴性乳腺癌是BC的异质性分子亚型。病理完全缓解(pCR)是衡量无复发和总生存期的重要替代指标。研究目的:本研究的目的是评估三阴性乳腺癌患者接受新辅助化疗后完全病理反应状态的相关临床和病理因素。材料与方法:回顾性分析2018年1月至2020年1月在paul Stradins临床大学医院接受新辅助化疗后手术的80例三阴性乳腺癌患者。26例(32.5%)为BRCA1/2致病变异携带者。结果:在所有研究组中,共有32.5% (n = 26)的患者和57.7% (n = 15)的BRCA1/2致病变异患者实现了pCR。47例患者接受以铂为主的新辅助化疗,19例患者(40.4%)达到完全病理缓解。pCR组患者Ki-67评分(p = 0.007)、BRCA1/2致病变异(p = 0.001)和年龄(p = 0.02)均明显高于非pCR组。pCR对无复发生存期(RFS)或总生存期(OS)没有显著影响。多因素分析显示,预处理N分期(临床淋巴结状态)是RFS和OS的独立预后因素。结论:BRCA1致病变异、高Ki67评分和年轻是三阴性乳腺癌病理完全缓解的预测因素,而临床淋巴结状态预测生存结果。
{"title":"Pathological complete response to neoadjuvant chemotherapy in triple negative breast cancer - single hospital experience.","authors":"Elina Sivina,&nbsp;Lubova Blumberga,&nbsp;Gunta Purkalne,&nbsp;Arvids Irmejs","doi":"10.1186/s13053-023-00249-1","DOIUrl":"https://doi.org/10.1186/s13053-023-00249-1","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer is a heterogeneous molecular subtype of BC. Pathological complete response (pCR) is an important surrogate marker for recurrence-free and overall survival.</p><p><strong>Aim of study: </strong>The aim of this study was to evaluate clinical and pathological factors that are associated with complete pathological response status in triple-negative breast cancer patients receiving neoadjuvant chemotherapy.</p><p><strong>Materials and methods: </strong>Eighty triple-negative breast cancer patients who underwent neoadjuvant chemotherapy followed by surgery at Pauls Stradins Clinical University Hospital between January 2018 and January 2020 were retrospectively analysed. Twenty-six patients (32.5%) were BRCA1/2 pathogenic variant carriers.</p><p><strong>Results: </strong>A total of 32.5% (n = 26) of patients in all study groups and 57.7% (n = 15) of patients with BRCA1/2 pathogenic variants achieved pCR. Forty-seven patients received platinum-based neoadjuvant chemotherapy, and 19 patients (40.4%) achieved complete pathological response. Patients in the pCR group presented with significantly higher Ki-67 scores (p = 0.007), BRCA1/2 pathogenic variants (p = 0.001) and younger age (p = 0.02) than those in the non-pCR group. pCR did not significantly impact recurrence-free survival (RFS) or overall survival (OS). Multivariate analysis revealed that pretreatment N stage (clinical nodal status) was an independent prognostic factor for RFS and OS.</p><p><strong>Conclusions: </strong>BRCA1 pathogenic variants, high Ki67 score and young age were predictors of pathological complete response, while clinical nodal status predicted survival outcomes in triple-negative breast cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"4"},"PeriodicalIF":1.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9187584","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: 2
Are population level familial risks and germline genetics meeting each other? 群体水平的家族性风险和种系遗传学是否相互吻合?
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-03-08 DOI: 10.1186/s13053-023-00247-3
Kari Hemminki, Xinjun Li, Asta Försti, Charis Eng

Large amounts of germline sequencing data have recently become available and we sought to compare these results with population-based family history data. Family studies are able to describe aggregation of any defined cancers in families. The Swedish Family-Cancer Database is the largest of its kind in the world, covering the Swedish families through nearly a century with all cancers in family members since the start of national cancer registration in 1958. The database allows estimation of familial risks, ages of cancer onset and the proportion of familial cancer in different family constellations. Here, we review the proportion of familial cancer for all common cancers and specify them based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40-50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate cancer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to high-risk proportions and age of onset.

大量的种系测序数据最近变得可用,我们试图将这些结果与基于人群的家族史数据进行比较。家族研究能够描述家族中任何特定癌症的聚集性。瑞典家庭癌症数据库是世界上同类数据库中最大的,涵盖了自1958年开始全国癌症登记以来近一个世纪以来瑞典家庭的所有癌症家庭成员。该数据库允许估计家族风险、癌症发病年龄以及家族癌症在不同家族中的比例。在这里,我们回顾了家族性癌症在所有常见癌症中的比例,并根据受影响个体的数量来指定它们。除少数癌症外,家族性癌症的发病年龄与所有癌症的发病年龄并无不同。家族性癌症的比例最高的是前列腺癌(26.4%)、乳腺癌(17.5%)和结直肠癌(15.7%),但有多人患病的高危家庭比例分别仅为2.8%、1%和0.9%。一项针对女性乳腺癌的大型测序研究发现,BRCA1和BRCA2突变可能占病例的2%(减去健康个体的比例),所有种系突变占病例的5.6%。早期发病是BRCA突变的一个明显特征。在遗传性结直肠癌中,Lynch综合征基因占主导地位。Lynch综合征外显率的大型研究表明,从40-50岁到80岁,其风险近似线性增加。有趣的新数据揭示了未知因素对家族风险的强烈影响。前列腺癌的高危种系遗传学以BRCA和其他DNA修复基因为特征。HOXB13编码一种转录因子,这种转录因子有助于前列腺癌的生殖系风险。与CIP2A基因多态性存在强交互作用。关于这些癌症的高危比例和发病年龄的家庭数据可以合理地适应新出现的常见癌症的生殖系景观。
{"title":"Are population level familial risks and germline genetics meeting each other?","authors":"Kari Hemminki,&nbsp;Xinjun Li,&nbsp;Asta Försti,&nbsp;Charis Eng","doi":"10.1186/s13053-023-00247-3","DOIUrl":"https://doi.org/10.1186/s13053-023-00247-3","url":null,"abstract":"<p><p>Large amounts of germline sequencing data have recently become available and we sought to compare these results with population-based family history data. Family studies are able to describe aggregation of any defined cancers in families. The Swedish Family-Cancer Database is the largest of its kind in the world, covering the Swedish families through nearly a century with all cancers in family members since the start of national cancer registration in 1958. The database allows estimation of familial risks, ages of cancer onset and the proportion of familial cancer in different family constellations. Here, we review the proportion of familial cancer for all common cancers and specify them based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40-50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate cancer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to high-risk proportions and age of onset.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"3"},"PeriodicalIF":1.7,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9136727","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: 1
The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer. 全基因组方法在鉴定结直肠癌遗传风险相关基因中的互补作用。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-01-28 DOI: 10.1186/s13053-023-00245-5
Olfat Ahmad, Asta Försti

The current understanding of the inherited risk of colorectal cancer (CRC) started with an observational clinical era in the late 19th century, which was followed by a genetic era starting in the late 20th century. Genome-wide linkage analysis allowed mapping several high-risk genes, which marked the beginning of the genetic era. The current high-throughput genomic phase includes genome-wide association study (GWAS) and genome-wide sequencing approaches which have revolutionized the conception of the inherited risk of CRC. On the one hand, GWAS has allowed the identification of multiple low risk loci correlated with CRC. On the other, genome-wide sequencing has led to the discovery of a second batch of high-to-moderate-risk genes that correlate to atypical familial CRC and polyposis syndromes. In contrast to other common cancers, which are usually dominated by a polygenic background, CRC risk is believed to be equally explained by monogenic and polygenic architectures, which jointly contribute to a quarter of familial clustering. Despite the fact that genome-wide approaches have allowed the identification of a continuum of responsible high-to-moderate-to-low-risk variants, much of the predisposition and familial clustering of CRC has not yet been explained. Other genetic, epigenetic and environmental factors might be playing important roles as well. In this review we aim to provide insights on the complementary roles played by different genomic approaches in allowing the current understanding of the genetic architecture of inherited CRC.

目前对结直肠癌(CRC)遗传风险的认识始于19世纪末的观察性临床时代,随后是20世纪末的遗传学时代。全基因组连锁分析可以绘制出几个高风险基因,这标志着遗传时代的开始。目前的高通量基因组阶段包括全基因组关联研究(GWAS)和全基因组测序方法,它们彻底改变了CRC遗传风险的概念。一方面,GWAS允许识别多个与CRC相关的低风险基因座。另一方面,全基因组测序已经发现了第二批与非典型家族性结直肠癌和息肉病综合征相关的高至中度风险基因。与其他通常由多基因背景主导的常见癌症不同,CRC的风险被认为同样可以由单基因和多基因结构来解释,它们共同促成了四分之一的家族聚类。尽管事实上,全基因组方法已经允许识别一系列负责任的高、中、低风险变异,但许多CRC的易感性和家族聚集性尚未得到解释。其他遗传、表观遗传和环境因素可能也起着重要作用。在这篇综述中,我们的目的是提供关于不同基因组方法在允许当前对遗传性CRC遗传结构的理解中所起的互补作用的见解。
{"title":"The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer.","authors":"Olfat Ahmad,&nbsp;Asta Försti","doi":"10.1186/s13053-023-00245-5","DOIUrl":"https://doi.org/10.1186/s13053-023-00245-5","url":null,"abstract":"<p><p>The current understanding of the inherited risk of colorectal cancer (CRC) started with an observational clinical era in the late 19<sup>th</sup> century, which was followed by a genetic era starting in the late 20<sup>th</sup> century. Genome-wide linkage analysis allowed mapping several high-risk genes, which marked the beginning of the genetic era. The current high-throughput genomic phase includes genome-wide association study (GWAS) and genome-wide sequencing approaches which have revolutionized the conception of the inherited risk of CRC. On the one hand, GWAS has allowed the identification of multiple low risk loci correlated with CRC. On the other, genome-wide sequencing has led to the discovery of a second batch of high-to-moderate-risk genes that correlate to atypical familial CRC and polyposis syndromes. In contrast to other common cancers, which are usually dominated by a polygenic background, CRC risk is believed to be equally explained by monogenic and polygenic architectures, which jointly contribute to a quarter of familial clustering. Despite the fact that genome-wide approaches have allowed the identification of a continuum of responsible high-to-moderate-to-low-risk variants, much of the predisposition and familial clustering of CRC has not yet been explained. Other genetic, epigenetic and environmental factors might be playing important roles as well. In this review we aim to provide insights on the complementary roles played by different genomic approaches in allowing the current understanding of the genetic architecture of inherited CRC.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2023-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10632258","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: 1
Germline heterozygous exons 8-11 pathogenic BARD1 gene deletion reported for the first time in a family with suspicion of a hereditary colorectal cancer syndrome: more than an incidental finding? 在一个怀疑遗传性结直肠癌综合征的家族中首次报道了种系杂合外显子8-11致病性BARD1基因缺失:不仅仅是偶然发现?
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2023-01-28 DOI: 10.1186/s13053-023-00246-4
Sergio Carrera, Ana Belén Rodríguez-Martínez, Intza Garin, Esther Sarasola, Cristina Martínez, Hiart Maortua, Almudena Callejo, Abigail Ruiz de Lobera, Alberto Muñoz, Nagore Miñambres, Pablo Jiménez-Labaig

Background: Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear.

Case presentation: We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease.

Conclusions: To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.

背景:结直肠癌(CRC)在发达国家是一种高度流行的疾病。遗传性孟德尔病因约占CRC病例的5%,其中Lynch综合征和家族性腺瘤性息肉病是最常见的形式。科学努力的重点是发现与结直肠癌相关的新的候选基因以及与已建立的癌症相关基因的表型的新关联。brca1相关环结构域(BARD1)基因有害种系变异与乳腺癌相对风险的适度增加有关,但它们与其他肿瘤(如CRC)的关系尚不清楚。病例介绍:我们提出的情况下,49岁的男性诊断为直肠腺癌,其母系符合阿姆斯特丹林奇综合征临床标准。基因检测证实在杂合中存在BARD1基因外显子8-11的种系致病性缺失。该家族的预测性遗传研究显示,该致病性变异存在于其已故的癌症患者亲属中,证实了该缺失与该疾病的共分离。结论:据我们所知,这是首次在家族性结直肠癌X型(FCCTX)综合征家族中检测到这种BARD1缺失的已发表的研究,该研究符合Lynch综合征的临床标准,但DNA错配修复(MMR)系统没有改变。这种偶然的生殖系发现是否是家族性结直肠聚集的原因仍有待科学论坛的阐明。患者应在特定的癌症遗传咨询单位仔细评估,以解释其他基因的假设偶然发现,原则上与最初的临床怀疑无关,但对其健康有潜在影响。
{"title":"Germline heterozygous exons 8-11 pathogenic BARD1 gene deletion reported for the first time in a family with suspicion of a hereditary colorectal cancer syndrome: more than an incidental finding?","authors":"Sergio Carrera,&nbsp;Ana Belén Rodríguez-Martínez,&nbsp;Intza Garin,&nbsp;Esther Sarasola,&nbsp;Cristina Martínez,&nbsp;Hiart Maortua,&nbsp;Almudena Callejo,&nbsp;Abigail Ruiz de Lobera,&nbsp;Alberto Muñoz,&nbsp;Nagore Miñambres,&nbsp;Pablo Jiménez-Labaig","doi":"10.1186/s13053-023-00246-4","DOIUrl":"https://doi.org/10.1186/s13053-023-00246-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear.</p><p><strong>Case presentation: </strong>We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"21 1","pages":"2"},"PeriodicalIF":1.7,"publicationDate":"2023-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149747","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
Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: results of a prospective cohort study. BRCA1/2致病变异携带者的心理因素和预防措施:一项前瞻性队列研究的结果
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2022-12-19 DOI: 10.1186/s13053-022-00244-y
Julia Dick, Anja Tüchler, Anne Brédart, Frank Vitinius, Kirsten Wassermann, Kerstin Rhiem, Rita K Schmutzler

Background: Women carrying BRCA1/2 pathogenic variants are exposed to elevated risks of developing breast cancer (BC) and are faced by a complex decision-making process on preventative measures, i.e., risk-reducing mastectomy (RRM), and intensified breast surveillance (IBS). In this prospective cohort study we investigated the effect of anxiety, personality factors and coping styles on the decision-making process on risk management options in women with pathogenic variants in BRCA1/2.

Methods: Breast cancer unaffected and affected women with a pathogenic variant in the BRCA1 or BRCA2 gene were psychologically evaluated immediately before (T0), 6 to 8 weeks (T1) and 6 to 8 months (T2) after the disclosure of their genetic test results. Uptake of RRM and IBS was assessed at T2. Psychological data were gathered using questionnaires on risk perception, personality factors, coping styles, decisional conflict, depression and anxiety, including the Hospital Anxiety and Depression Scale (HADS). We performed tests on statistical significance and fitted a logistic regression based on significance level.

Results: A total of 98 women were included in the analysis. Baseline anxiety levels in women opting for RRM were high but decreased over time, while they increased in women opting for intensified breast surveillance (IBS). Elevated levels of anxiety after genetic test result disclosure (T1) were associated with the decision to undergo RRM (p < 0.01; OR = 1.2, 95% CI = 1.05-1.42), while personal BC history and personality factors seemed to be less relevant.

Conclusions: Considering psychosocial factors influencing the decision-making process of women with pathogenic variants in BRCA1/2 may help improving their genetic and psychological counselling. When opting for IBS they may profit from additional medical and psychological counselling.

Trial registration: Retrospectively registered at the German Clinical Trials Register under DRKS00027566 on January 13, 2022.

背景:携带BRCA1/2致病变异的女性患乳腺癌(BC)的风险升高,并且面临着一个复杂的预防措施决策过程,即降低风险的乳房切除术(RRM)和加强乳房监测(IBS)。在这项前瞻性队列研究中,我们调查了焦虑、人格因素和应对方式对BRCA1/2致病变异女性风险管理选择决策过程的影响。方法:对BRCA1或BRCA2基因致病性变异的未受影响和未受影响的乳腺癌患者在基因检测结果披露前(T0)、6 ~ 8周(T1)和6 ~ 8个月(T2)进行心理评估。在T2时评估RRM和IBS的摄取情况。心理数据采用风险感知、人格因素、应对方式、决策冲突、抑郁和焦虑问卷,包括医院焦虑和抑郁量表(HADS)。我们进行了统计显著性检验,并根据显著性水平拟合了逻辑回归。结果:共有98名女性被纳入分析。选择RRM的妇女的基线焦虑水平很高,但随着时间的推移而下降,而选择强化乳房监测(IBS)的妇女的基线焦虑水平则有所增加。基因检测结果披露(T1)后焦虑水平升高与接受RRM的决定相关(p)结论:考虑影响BRCA1/2致病变异女性决策过程的社会心理因素可能有助于改善其遗传和心理咨询。当选择肠易激综合症时,他们可能会从额外的医疗和心理咨询中获益。试验注册:于2022年1月13日根据DRKS00027566在德国临床试验注册中心回顾性注册。
{"title":"Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: results of a prospective cohort study.","authors":"Julia Dick,&nbsp;Anja Tüchler,&nbsp;Anne Brédart,&nbsp;Frank Vitinius,&nbsp;Kirsten Wassermann,&nbsp;Kerstin Rhiem,&nbsp;Rita K Schmutzler","doi":"10.1186/s13053-022-00244-y","DOIUrl":"https://doi.org/10.1186/s13053-022-00244-y","url":null,"abstract":"<p><strong>Background: </strong>Women carrying BRCA1/2 pathogenic variants are exposed to elevated risks of developing breast cancer (BC) and are faced by a complex decision-making process on preventative measures, i.e., risk-reducing mastectomy (RRM), and intensified breast surveillance (IBS). In this prospective cohort study we investigated the effect of anxiety, personality factors and coping styles on the decision-making process on risk management options in women with pathogenic variants in BRCA1/2.</p><p><strong>Methods: </strong>Breast cancer unaffected and affected women with a pathogenic variant in the BRCA1 or BRCA2 gene were psychologically evaluated immediately before (T0), 6 to 8 weeks (T1) and 6 to 8 months (T2) after the disclosure of their genetic test results. Uptake of RRM and IBS was assessed at T2. Psychological data were gathered using questionnaires on risk perception, personality factors, coping styles, decisional conflict, depression and anxiety, including the Hospital Anxiety and Depression Scale (HADS). We performed tests on statistical significance and fitted a logistic regression based on significance level.</p><p><strong>Results: </strong>A total of 98 women were included in the analysis. Baseline anxiety levels in women opting for RRM were high but decreased over time, while they increased in women opting for intensified breast surveillance (IBS). Elevated levels of anxiety after genetic test result disclosure (T1) were associated with the decision to undergo RRM (p < 0.01; OR = 1.2, 95% CI = 1.05-1.42), while personal BC history and personality factors seemed to be less relevant.</p><p><strong>Conclusions: </strong>Considering psychosocial factors influencing the decision-making process of women with pathogenic variants in BRCA1/2 may help improving their genetic and psychological counselling. When opting for IBS they may profit from additional medical and psychological counselling.</p><p><strong>Trial registration: </strong>Retrospectively registered at the German Clinical Trials Register under DRKS00027566 on January 13, 2022.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"20 1","pages":"38"},"PeriodicalIF":1.7,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10410625","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: 1
The Prospective Lynch Syndrome Database: background, design, main results and complete MySQL code. 前瞻性Lynch综合征数据库:背景、设计、主要结果和完整的MySQL代码。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2022-11-21 DOI: 10.1186/s13053-022-00243-z
Pål Møller

A brief description of why and for which purposes the Prospective Lynch Syndrome Database was established, the principles and design, and the main classes of results are given. Data input is assumption-free input enabling validation of paradigms used to explain the results. The design is considering cancer/age as discrete events to occur or not in a time dimension in a closed room compliant with population genetic paradigms and last centuries developing paradigms of interpreting discrete events reflecting conditional and/or co-occurring stochastic probabilities. Which may be in contrast to the paradigm that any observed event has a cause. The results may indicate that some current paradigms on carcinogenesis should be reconsidered. The complete analytic code in MySQL© syntax together with a flowchart illustrating how the different pieces of codes interrelate are included as supplementary files, enabling third parties to use or modify the code to examine prospectively observed events in their own activities when referring to this report as the source.

简要介绍了建立前瞻性Lynch综合征数据库的原因和目的,原则和设计,以及结果的主要类别。数据输入是无假设的输入,可以验证用于解释结果的范式。该设计将癌症/年龄视为离散事件,在一个封闭的房间里,在一个时间维度上发生或不发生,符合人口遗传范式和上个世纪发展的范式,这些范式解释了反映条件和/或共同发生的随机概率的离散事件。这可能与任何观察到的事件都有原因的范式相反。这一结果可能表明,目前的一些关于癌变的范式应该重新考虑。MySQL©语法中的完整分析代码与说明不同代码片段如何相互关联的流程图一起作为补充文件包含,使第三方能够使用或修改代码,以便在引用此报告作为源时检查自己活动中的前瞻性观察事件。
{"title":"The Prospective Lynch Syndrome Database: background, design, main results and complete MySQL code.","authors":"Pål Møller","doi":"10.1186/s13053-022-00243-z","DOIUrl":"https://doi.org/10.1186/s13053-022-00243-z","url":null,"abstract":"<p><p>A brief description of why and for which purposes the Prospective Lynch Syndrome Database was established, the principles and design, and the main classes of results are given. Data input is assumption-free input enabling validation of paradigms used to explain the results. The design is considering cancer/age as discrete events to occur or not in a time dimension in a closed room compliant with population genetic paradigms and last centuries developing paradigms of interpreting discrete events reflecting conditional and/or co-occurring stochastic probabilities. Which may be in contrast to the paradigm that any observed event has a cause. The results may indicate that some current paradigms on carcinogenesis should be reconsidered. The complete analytic code in MySQL© syntax together with a flowchart illustrating how the different pieces of codes interrelate are included as supplementary files, enabling third parties to use or modify the code to examine prospectively observed events in their own activities when referring to this report as the source.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"20 1","pages":"37"},"PeriodicalIF":1.7,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10327892","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: 3
Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium. 林奇综合征的结直肠癌发病率:前瞻性林奇综合征数据库与国际错配修复联盟的结果比较。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2022-10-01 DOI: 10.1186/s13053-022-00241-1
Pål Møller, Toni Seppälä, James G Dowty, Saskia Haupt, Mev Dominguez-Valentin, Lone Sunde, Inge Bernstein, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Elizabeth Half, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Rodney J Scott, Lior Katz, Ido Laish, Elez Vainer, Carlos Alberto Vaccaro, Dirce Maria Carraro, Nathan Gluck, Naim Abu-Freha, Aine Stakelum, Rory Kennelly, Des Winter, Benedito Mauro Rossi, Marc Greenblatt, Mabel Bohorquez, Harsh Sheth, Maria Grazia Tibiletti, Leonardo S Lino-Silva, Karoline Horisberger, Carmen Portenkirchner, Ivana Nascimento, Norma Teresa Rossi, Leandro Apolinário da Silva, Huw Thomas, Attila Zaránd, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepisto, Päivi Peltomäki, Christina Therkildsen, Lars Joachim Lindberg, Ole Thorlacius-Ussing, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Aída Falcón de Vargas, Andrew Latchford, Anne-Marie Gerdes, Ann-Sofie Backman, Carmen Guillén-Ponce, Carrie Snyder, Charlotte K Lautrup, David Amor, Edenir Palmero, Elena Stoffel, Floor Duijkers, Michael J Hall, Heather Hampel, Heinric Williams, Henrik Okkels, Jan Lubiński, Jeanette Reece, Joanne Ngeow, Jose G Guillem, Julie Arnold, Karin Wadt, Kevin Monahan, Leigha Senter, Lene J Rasmussen, Liselotte P van Hest, Luigi Ricciardiello, Maija R J Kohonen-Corish, Marjolijn J L Ligtenberg, Melissa Southey, Melyssa Aronson, Mohd N Zahary, N Jewel Samadder, Nicola Poplawski, Nicoline Hoogerbrugge, Patrick J Morrison, Paul James, Grant Lee, Rakefet Chen-Shtoyerman, Ravindran Ankathil, Rish Pai, Robyn Ward, Susan Parry, Tadeusz Dębniak, Thomas John, Thomas van Overeem Hansen, Trinidad Caldés, Tatsuro Yamaguchi, Verónica Barca-Tierno, Pilar Garre, Giulia Martina Cavestro, Jürgen Weitz, Silke Redler, Reinhard Büttner, Vincent Heuveline, John L Hopper, Aung Ko Win, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A Newcomb, Jane Figueiredo, Daniel D Buchanan, Stephen N Thibodeau, Sanne W Ten Broeke, Eivind Hovig, Sigve Nakken, Marta Pineda, Nuria Dueñas, Joan Brunet, Kate Green, Fiona Lalloo, Katie Newton, Emma J Crosbie, Miriam Mints, Douglas Tjandra, Florencia Neffa, Patricia Esperon, Revital Kariv, Guy Rosner, Walter Hernán Pavicic, Pablo Kalfayan, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Martin, Gabriela Moslein, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Mark A Jenkins

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants.

Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands.

Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups.

Conclusions: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

目的:比较 PLSD 和 IMRC 队列中 MMR 基因致病性变异携带者的结直肠癌(CRC)发病率,其中只有前者对所有参与者进行了强制性结肠镜监测:在干预组中计算了癌症发病率,该干预组由错配修复基因(path_MMR)致病性或可能致病性变异的确诊携带者组成,由前瞻性林奇综合征数据库(PLSD)进行前瞻性跟踪。所有患者都接受了结肠镜检查,并在发现息肉时进行了息肉切除术。与国际错配修复联盟(IMRC)报告的回顾性队列进行了比较。该队列由林奇综合征疑似患者的一级或二级亲属中经证实和推断的路径_MMR携带者组成:结果:在 PLSD 中,8153 名受试者接受了共计 67604 年的结肠镜随访监测,其中 578 名携带者确诊为 CRC。路径_MLH1携带者在70岁时的平均累积癌症发病率为:男性52%,女性41%;路径_MSH2为50%,女性39%;路径_MSH6为13%,男性17%;路径_PMS2为11%,女性8%。相比之下,在IMRC队列中,相应的累积发病率分别为40%和27%;34%和23%;16%和8%以及7%和6%。仅比较这两个系列中的欧洲带原者,也得出了类似的结果。PLSD 系列中的数字无法单独比较其他大洲携带者的情况。在所有回顾性研究组中,25年的累积发病率均小于1%:接受结肠镜监测和息肉切除术的路径_MLH1和路径_MSH2携带者的前瞻性观察CRC发病率(PLSD)高于回顾性系列(IMRC),而路径_MSH6携带者的发病率并未降低。这些结果与预期相反。接受结肠镜检查的 path_PMS2 携带者 50 岁前的 CRC 点发病率有所降低,但并不明显。
{"title":"Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.","authors":"Pål Møller, Toni Seppälä, James G Dowty, Saskia Haupt, Mev Dominguez-Valentin, Lone Sunde, Inge Bernstein, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Elizabeth Half, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Rodney J Scott, Lior Katz, Ido Laish, Elez Vainer, Carlos Alberto Vaccaro, Dirce Maria Carraro, Nathan Gluck, Naim Abu-Freha, Aine Stakelum, Rory Kennelly, Des Winter, Benedito Mauro Rossi, Marc Greenblatt, Mabel Bohorquez, Harsh Sheth, Maria Grazia Tibiletti, Leonardo S Lino-Silva, Karoline Horisberger, Carmen Portenkirchner, Ivana Nascimento, Norma Teresa Rossi, Leandro Apolinário da Silva, Huw Thomas, Attila Zaránd, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepisto, Päivi Peltomäki, Christina Therkildsen, Lars Joachim Lindberg, Ole Thorlacius-Ussing, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Aída Falcón de Vargas, Andrew Latchford, Anne-Marie Gerdes, Ann-Sofie Backman, Carmen Guillén-Ponce, Carrie Snyder, Charlotte K Lautrup, David Amor, Edenir Palmero, Elena Stoffel, Floor Duijkers, Michael J Hall, Heather Hampel, Heinric Williams, Henrik Okkels, Jan Lubiński, Jeanette Reece, Joanne Ngeow, Jose G Guillem, Julie Arnold, Karin Wadt, Kevin Monahan, Leigha Senter, Lene J Rasmussen, Liselotte P van Hest, Luigi Ricciardiello, Maija R J Kohonen-Corish, Marjolijn J L Ligtenberg, Melissa Southey, Melyssa Aronson, Mohd N Zahary, N Jewel Samadder, Nicola Poplawski, Nicoline Hoogerbrugge, Patrick J Morrison, Paul James, Grant Lee, Rakefet Chen-Shtoyerman, Ravindran Ankathil, Rish Pai, Robyn Ward, Susan Parry, Tadeusz Dębniak, Thomas John, Thomas van Overeem Hansen, Trinidad Caldés, Tatsuro Yamaguchi, Verónica Barca-Tierno, Pilar Garre, Giulia Martina Cavestro, Jürgen Weitz, Silke Redler, Reinhard Büttner, Vincent Heuveline, John L Hopper, Aung Ko Win, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A Newcomb, Jane Figueiredo, Daniel D Buchanan, Stephen N Thibodeau, Sanne W Ten Broeke, Eivind Hovig, Sigve Nakken, Marta Pineda, Nuria Dueñas, Joan Brunet, Kate Green, Fiona Lalloo, Katie Newton, Emma J Crosbie, Miriam Mints, Douglas Tjandra, Florencia Neffa, Patricia Esperon, Revital Kariv, Guy Rosner, Walter Hernán Pavicic, Pablo Kalfayan, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Martin, Gabriela Moslein, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Mark A Jenkins","doi":"10.1186/s13053-022-00241-1","DOIUrl":"10.1186/s13053-022-00241-1","url":null,"abstract":"<p><strong>Objective: </strong>To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants.</p><p><strong>Methods: </strong>CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands.</p><p><strong>Results: </strong>In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups.</p><p><strong>Conclusions: </strong>Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"20 1","pages":"36"},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918770","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
Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan 在巴基斯坦的一个学术医疗中心,在疑似遗传性乳腺癌患者中使用靶向下一代测序小组和基因型-表型相关性的种系致病变异谱
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2022-06-16 DOI: 10.1186/s13053-022-00232-2
Akbar, Fizza, Siddiqui, Zahraa, Waheed, Muhammad Talha, Ehsan, Lubaina, Ali, Syed Ibaad, Wiquar, Hajra, Valimohammed, Azmina Tajuddin, Khan, Shaista, Vohra, Lubna, Zeeshan, Sana, Rashid, Yasmin, Moosajee, Munira, Jabbar, Adnan Abdul, Zahir, Muhammad Nauman, Zahid, Naila, Soomro, Rufina, Ullah, Najeeb Niamat, Ahmad, Imran, Haider, Ghulam, Ansari, Uzair, Rizvi, Arjumand, Mehboobali, Arif, Sattar, Abida, Kirmani, Salman
Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5–10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher’s exact, Pearson’s chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5–48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42–5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.
乳腺癌是妇女中最常见的恶性肿瘤,每年影响150多万妇女,是全球妇女与癌症有关的死亡人数最多的。遗传性乳腺癌(HBC)是乳腺癌的一个重要亚型,占总病例的5-10%。然而,在中低收入国家(LMICs),不同种族的人群特异性HBC风险及其与某些临床特征的相关性仍未得到研究。2017年5月至2020年4月到HBC诊所就诊并进行多基因面板检测的患者回顾性图表回顾。采用描述性统计和推断性统计分析患者的临床特征。分类变量采用Fisher精确检验、Pearson卡方检验和Logistic回归分析,定量变量采用Wilcoxon秩和检验。两独立组间比较采用Mann-Whitney检验。p值< 0.05时认为结果显著。在273名患者中,22%的检测结果呈阳性,37%的人患有VUS, 41%的人基因检测结果为阴性。55%的阳性患者有BRCA1或BRCA2的致病变异,而其余的阳性结果归因于其他基因。与VUS阳性结果的患者相比,VUS阳性结果的患者在诊断时年龄更小;中位年龄37.5岁,IQR(四分位数间距)(31.5-48)。此外,三阴性乳腺癌(TNBC)患者的阳性结果几乎是三倍(OR = 2.79, CI = 1.42-5.48 p = 0.003)。在所有阳性结果的患者中,25%的患者有乳腺癌和/或相关癌症的阴性家族史。在我们的HBC诊所中,我们观察到我们的阳性结果率是相当的,但在其他人群中报道的范围的高端。事实上,几乎一半的患者在BRCA1/2以外的基因中具有致病性或可能致病性变异,并且如果只进行BRCA1/2检测,我们的检测阳性率仅为12.8%,这突出了扩展的多基因面板检测的重要性。随着数据库的扩展和协议驱动的转诊在全国范围内进行,我们对人群中HBC遗传结构的了解将继续增加。
{"title":"Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan","authors":"Akbar, Fizza, Siddiqui, Zahraa, Waheed, Muhammad Talha, Ehsan, Lubaina, Ali, Syed Ibaad, Wiquar, Hajra, Valimohammed, Azmina Tajuddin, Khan, Shaista, Vohra, Lubna, Zeeshan, Sana, Rashid, Yasmin, Moosajee, Munira, Jabbar, Adnan Abdul, Zahir, Muhammad Nauman, Zahid, Naila, Soomro, Rufina, Ullah, Najeeb Niamat, Ahmad, Imran, Haider, Ghulam, Ansari, Uzair, Rizvi, Arjumand, Mehboobali, Arif, Sattar, Abida, Kirmani, Salman","doi":"10.1186/s13053-022-00232-2","DOIUrl":"https://doi.org/10.1186/s13053-022-00232-2","url":null,"abstract":"Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5–10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher’s exact, Pearson’s chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5–48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42–5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"243 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138529474","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: 5
Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore 临床特征和基因检测结果怀疑遗传性周围神经鞘肿瘤在新加坡三级癌症机构
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2022-06-13 DOI: 10.1186/s13053-022-00230-4
J. Loh, P. Ong, D. Goh, M. Puhaindran, B. Vellayappan, S. Ow, Gloria Chan, Soo-Chin Lee
{"title":"Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore","authors":"J. Loh, P. Ong, D. Goh, M. Puhaindran, B. Vellayappan, S. Ow, Gloria Chan, Soo-Chin Lee","doi":"10.1186/s13053-022-00230-4","DOIUrl":"https://doi.org/10.1186/s13053-022-00230-4","url":null,"abstract":"","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"20 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65767050","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
期刊
Hereditary Cancer in Clinical Practice
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1