Familial Cancer最新文献_第7页

Cascade genetic counseling and testing in hereditary syndromes: inherited cardiovascular disease as a model: a narrative review. 遗传综合征的级联遗传咨询和检测：以遗传性心血管疾病为模型：综述。

IF 1.8 4区医学

Familial Cancer Pub Date : 2024-06-01 Epub Date: 2024-01-06 DOI: 10.1007/s10689-023-00356-x

Laura A Grutters, Imke Christiaans

{"title":"Cascade genetic counseling and testing in hereditary syndromes: inherited cardiovascular disease as a model: a narrative review.","authors":"Laura A Grutters, Imke Christiaans","doi":"10.1007/s10689-023-00356-x","DOIUrl":"10.1007/s10689-023-00356-x","url":null,"abstract":"Inherited cardiovascular diseases cover the inherited cardiovascular disease familial hypercholesterolemia and inherited cardiac diseases, like inherited cardiomyopathies and inherited arrhythmia syndromes. Cascade genetic counseling and testing in inherited cardiovascular diseases have had three decades of academic attention. Inherited cardiovascular diseases affect around 1-2% of the population worldwide and cascade genetic counseling and testing are considered valuable since preventive measures and/or treatments are available. Cascade genetic counseling via a family-mediated approach leads to an uptake of genetic counseling and testing among at-risk relatives of around 40% one year after identification of the causal variant in the proband, with uptake remaining far from complete on the long-term. These findings align with uptake rates among relatives at-risk for other late onset medically actionable hereditary diseases, like hereditary cancer syndromes. Previous interventions to increase uptake have focused on optimizing the process of informing relatives through the proband and on contacting relatives directly. However, despite successful information dissemination to at-risk relatives, these approaches had little or no effect on uptake. The limited research into the barriers that impede at-risk relatives from seeking counseling has revealed knowledge, attitudinal, social and practical barriers but it remains unknown how these factors contribute to the decision-making process for seeking counseling in at-risk relatives. A significant effect on uptake of genetic testing has only been reached in the setting of familial hypercholesterolemia, where active information provision was accompanied by a reduction of health-system-related barriers. We propose that more research is needed on barriers -including health-system-related barriers- and how they hinder counseling and testing in at-risk relatives, so that uptake can be optimized by (adjusted) interventions.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"155-164"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110931","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

Cascade testing in Italian Hereditary Breast Ovarian Cancer families: a missed opportunity for cancer prevention? 意大利遗传性乳腺癌家族级联检测:错过了预防癌症的机会吗?

IF 1.8 4区医学

Familial Cancer Pub Date : 2024-06-01 Epub Date: 2023-11-16 DOI: 10.1007/s10689-023-00349-w

Lucia Trevisan, Lea Godino, Linda Battistuzzi, Giovanni Innella, Elena Luppi, Giulia Buzzatti, Viviana Gismondi, Eva Blondeaux, Luigina Ada Bonelli, Daniela Turchetti, Liliana Varesco

{"title":"Cascade testing in Italian Hereditary Breast Ovarian Cancer families: a missed opportunity for cancer prevention?","authors":"Lucia Trevisan, Lea Godino, Linda Battistuzzi, Giovanni Innella, Elena Luppi, Giulia Buzzatti, Viviana Gismondi, Eva Blondeaux, Luigina Ada Bonelli, Daniela Turchetti, Liliana Varesco","doi":"10.1007/s10689-023-00349-w","DOIUrl":"10.1007/s10689-023-00349-w","url":null,"abstract":"Healthy carriers of BRCA1/2 pathogenic variants (PVs) may benefit from risk-reducing measures of proven efficacy. The main approach to identify these individuals is cascade testing, and strategies to support this complex process are under investigation. In Italy, cascade testing has received little attention; therefore, we analyzed the uptake and characteristics of BRCA1/2 cascade testing in families diagnosed with HBOC between 2017 and 2019 at two Italian genetics centers. All blood relatives aged 18 years or older at September 2022 and who could be involved in the first step of cascade testing (i.e., all the living relatives closest to the proband) were included. In addition to first-degree relatives, individuals who were second-, third- or fourth-degree relatives were included if the closest relative(s) was/were deceased. Overall, 213 families were included (103, Genoa; 110, Bologna). Most probands were women affected by breast and/or ovarian cancer (86.4%, Genoa; 84.5%, Bologna), and the branch segregating the PV was known/suspected in 62% of families (62.1%, Genoa; 60.9%, Bologna). Overall, the uptake of cascade testing was 22.8% (25.8%, Genoa; 19.9%, Bologna; OR = 0.59: 95%CI 0.43-0.82). It was strongly associated with female gender (OR = 3.31, 95%CI 2.38-4.59), age ≤ 70 years (< 30 years OR = 3.48, 95%CI 1.85-6.56; 30-70 years OR = 3.08, 95%CI 2.01-4.71), first-degree relationship with the proband (OR = 16.61, 95%CI 10.50-26.28) and segregation of the PV in both the maternal (OR = 2.54, 95%CI 1.72-3.75) and the paternal branch (OR = 4.62, 95%CI 3.09-6.91). These real-world data may be important to inform the design and implementation of strategies aimed at improving the uptake of HBOC cascade testing in Italy.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"197-207"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648759","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

Cascade genetic testing: an underutilized pathway to equitable cancer care? 级联基因检测：未得到充分利用的公平癌症治疗途径？

IF 1.8 4区医学

Familial Cancer Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s10689-024-00367-2

Roni Nitecki Wilke, Erica M Bednar, Sara Pirzadeh-Miller, Sayoni Lahiri, Isabel C Scarinci, Charles A Leath Iii, Melissa K Frey, Karen H Lu, J Alejandro Rauh-Hain

{"title":"Cascade genetic testing: an underutilized pathway to equitable cancer care?","authors":"Roni Nitecki Wilke, Erica M Bednar, Sara Pirzadeh-Miller, Sayoni Lahiri, Isabel C Scarinci, Charles A Leath Iii, Melissa K Frey, Karen H Lu, J Alejandro Rauh-Hain","doi":"10.1007/s10689-024-00367-2","DOIUrl":"10.1007/s10689-024-00367-2","url":null,"abstract":"The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the \"cascade\" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"141-145"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921500","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

Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes: disclosure of genetic test results to relatives. 携带乳腺癌基因致病种系变异的转移性前列腺癌男性患者：向亲属披露基因检测结果。

IF 1.8 4区医学

Familial Cancer Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1007/s10689-024-00377-0

Michiel Vlaming, Margreet G E M Ausems, Gina Schijven, Inge M van Oort, C Marleen Kets, Fenne L Komdeur, Lizet E van der Kolk, Rogier A Oldenburg, Rolf H Sijmons, Lambertus A L M Kiemeney, Eveline M A Bleiker

{"title":"Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes: disclosure of genetic test results to relatives.","authors":"Michiel Vlaming, Margreet G E M Ausems, Gina Schijven, Inge M van Oort, C Marleen Kets, Fenne L Komdeur, Lizet E van der Kolk, Rogier A Oldenburg, Rolf H Sijmons, Lambertus A L M Kiemeney, Eveline M A Bleiker","doi":"10.1007/s10689-024-00377-0","DOIUrl":"10.1007/s10689-024-00377-0","url":null,"abstract":"Some patients with metastatic prostate cancer carry a pathogenic germline variant (PV) in a gene, that is mainly associated with an increased risk of breast cancer in women. If they test positive for such a PV, prostate cancer patients are encouraged to disclose the genetic test result to relatives who are at risk in case the carrier status changes the relatives' medical care. Our study aimed to investigate how men who learned they carry a PV in BRCA1, BRCA2, PALB2, CHEK2 or ATM disclosed their carrier status to at-risk relatives and to assess the possible psychological burden for the carrier and their perception of the burden for relatives. In total, 23 men with metastatic prostate cancer carrying a PV completed the IRI questionnaire about family communication; 14 also participated in a semi-structured interview. Patients felt highly confident in discussing the genetic test result with relatives. The diagnosis of prostate cancer was experienced as a burden, whereas being informed about genetic testing results did in most cases not add to this burden. Two patients encountered negative experiences with family communication, as they considered the genetic test result to be more urgent than their relatives. This mixed-methods study shows that metastatic prostate cancer patients with a PV in genes mainly associated with increased risk of breast cancer feel well-equipped to communicate about this predisposition in their families. Carriers felt motivated to disclose their genetic test result to relatives. Most of them indicated that the disclosure was not experienced as a psychological burden.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"165-175"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897981","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

Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study 激素避孕对林奇综合征患者子宫内膜组织学的影响，一项回顾性试点研究

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-30 DOI: 10.1007/s10689-024-00387-y

Marie Mawet, Clémence Evrevin, Antoine Dardenne, Frédéric Kridelka, Axelle Pintiaux, Nathalie Chabbert-Buffet

{"title":"Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study","authors":"Marie Mawet, Clémence Evrevin, Antoine Dardenne, Frédéric Kridelka, Axelle Pintiaux, Nathalie Chabbert-Buffet","doi":"10.1007/s10689-024-00387-y","DOIUrl":"https://doi.org/10.1007/s10689-024-00387-y","url":null,"abstract":"Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"28 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839490","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

A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America 拉丁美洲 MUTYH 基因致病变体谱系的全面特征描述

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-30 DOI: 10.1007/s10689-024-00382-3

Patricia Esperon, Florencia Neffa, Walter Pavicic, Florencia Spirandelli, Karin Alvarez, María José Mullins, Benedito Mauro Rossi, Rodrigo Felipe Góngora e Silva, Carlos Vaccaro, Francisco Lopéz-Köstner, Jorge Rugeles, Adriana Della Valle, Mev Dominguez-Valentin

{"title":"A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America","authors":"Patricia Esperon, Florencia Neffa, Walter Pavicic, Florencia Spirandelli, Karin Alvarez, María José Mullins, Benedito Mauro Rossi, Rodrigo Felipe Góngora e Silva, Carlos Vaccaro, Francisco Lopéz-Köstner, Jorge Rugeles, Adriana Della Valle, Mev Dominguez-Valentin","doi":"10.1007/s10689-024-00382-3","DOIUrl":"https://doi.org/10.1007/s10689-024-00382-3","url":null,"abstract":"MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31–71) and 49.90 years (range 27–87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"28 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839491","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

Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family 低资源国家的 CMMRD 诊断和管理策略：一个突尼斯家庭的报告

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-30 DOI: 10.1007/s10689-024-00386-z

Rania Abdelmaksoud-Dammak, Nihel Ammous-Boukhris, Dorra BenAyed-Guerfali, Yassine Gdoura, Imen Boujelben, Souhir Guidara, Slim Charfi, Wiem Boudabbous, Saloua Ammar, Wiem Rhaiem, Mohamed Zaher Boudawara, Hassen Kamoun, Tahya Sallemi-Boudawara, Riadh Mhiri, Raja Mokdad-Gargouri

{"title":"Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family","authors":"Rania Abdelmaksoud-Dammak, Nihel Ammous-Boukhris, Dorra BenAyed-Guerfali, Yassine Gdoura, Imen Boujelben, Souhir Guidara, Slim Charfi, Wiem Boudabbous, Saloua Ammar, Wiem Rhaiem, Mohamed Zaher Boudawara, Hassen Kamoun, Tahya Sallemi-Boudawara, Riadh Mhiri, Raja Mokdad-Gargouri","doi":"10.1007/s10689-024-00386-z","DOIUrl":"https://doi.org/10.1007/s10689-024-00386-z","url":null,"abstract":"Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"11 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839524","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

Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer 对胰腺癌高危人群进行监测的方面和结果

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-15 DOI: 10.1007/s10689-024-00368-1

Aleksander M. Bogdanski, Jeanin E. van Hooft, Bas Boekestijn, Bert A. Bonsing, Martin N. J. M. Wasser, Derk C. F. Klatte, Monique E. van Leerdam

引用次数: 0

Clinical features of prostate cancer by polygenic risk score 多基因风险评分显示的前列腺癌临床特征

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-15 DOI: 10.1007/s10689-024-00369-0

Christina Spears, Menglin Xu, Abigail Shoben, Shawn Dason, Amanda Ewart Toland, Lindsey Byrne

{"title":"Clinical features of prostate cancer by polygenic risk score","authors":"Christina Spears, Menglin Xu, Abigail Shoben, Shawn Dason, Amanda Ewart Toland, Lindsey Byrne","doi":"10.1007/s10689-024-00369-0","DOIUrl":"https://doi.org/10.1007/s10689-024-00369-0","url":null,"abstract":"Genome-wide association studies have identified more than 290 single nucleotide variants (SNVs) associated with prostate cancer. These SNVs can be combined to generate a Polygenic Risk Score (PRS), which estimates an individual’s risk to develop prostate cancer. Identifying individuals at higher risk for prostate cancer using PRS could allow for personalized screening recommendations, improve current screening tools, and potentially result in improved survival rates, but more research is needed before incorporating them into clinical use. Our study aimed to investigate associations between PRS and clinical factors in affected individuals, including age of diagnosis, metastases, histology, International Society of Urological Pathology (ISUP) Grade Group (GG) and family history of prostate cancer, while taking into account germline genetic testing in known prostate cancer related genes. To evaluate the relationship between these clinical factors and PRS, a quantitative retrospective chart review of 250 individuals of European ancestry diagnosed with prostate cancer who received genetic counseling services at The Ohio State University’s Genitourinary Cancer Genetics Clinic and a 72-SNV PRS through Ambry Genetics, was performed. We found significant associations between higher PRS and younger age of diagnosis (p = 0.002), lower frequency of metastases (p = 0.006), and having a first-degree relative diagnosed with prostate cancer (p = 0.024). We did not observe significant associations between PRS and ISUP GG, histology or a having a second-degree relative with prostate cancer. These findings provide insights into features associated with higher PRS, but larger multi-ancestral studies using PRS that are informative across populations are needed to understand its clinical utility.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575228","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

Evaluation of EGFR and COX pathway inhibition in human colon organoids of serrated polyposis and other hereditary cancer syndromes 评估锯齿状息肉病和其他遗传性癌症综合征人结肠器官组织中表皮生长因子受体和 COX 通路的抑制作用

IF 2.2 4区医学

Familial Cancer Pub Date : 2024-04-12 DOI: 10.1007/s10689-024-00370-7

Priyanka Kanth, Mark W. Hazel, John C. Schell, Jared Rutter, Ruoxin Yao, Alyssa P. Mills, Don A. Delker

{"title":"Evaluation of EGFR and COX pathway inhibition in human colon organoids of serrated polyposis and other hereditary cancer syndromes","authors":"Priyanka Kanth, Mark W. Hazel, John C. Schell, Jared Rutter, Ruoxin Yao, Alyssa P. Mills, Don A. Delker","doi":"10.1007/s10689-024-00370-7","DOIUrl":"https://doi.org/10.1007/s10689-024-00370-7","url":null,"abstract":"Serrated polyposis syndrome (SPS) presents with multiple sessile serrated lesions (SSL) in the large intestine and confers increased colorectal cancer (CRC) risk. However, the etiology of SPS is not known. SSL-derived organoids have not been previously studied but may help provide insights into SPS pathogenesis and identify novel biomarkers and chemopreventive strategies. This study examined effects of EGFR and COX pathway inhibition in organoid cultures derived from uninvolved colon and polyps of SPS patients. We also compared with organoids representing the hereditary gastrointestinal syndromes, Familial Adenomatous Polyposis (FAP) and Lynch syndrome (LS). Eighteen total organoid colon cultures were generated from uninvolved colon and polyps in SPS, FAP, LS, and non-syndromic screening colonoscopy patients. BRAF and KRAS mutation status was determined for each culture. Erlotinib (EGFR inhibitor) and sulindac (COX inhibitor) were applied individually and in combination. A 44-target gene custom mRNA panel (including WNT and COX pathway genes) and a 798-gene microRNA gene panel were used to quantitate organoid RNA expression by NanoString analysis. Erlotinib treatment significantly decreased levels of mRNAs associated with WNT and MAPK kinase signaling in organoids from uninvolved colon from all four patient categories and from all SSL and adenomatous polyps. Sulindac did not change the mRNA profile in any culture. Our findings suggest that EGFR inhibitors may contribute to the chemopreventive treatment of SSLs. These findings may also facilitate clinical trial design using these agents in SPS patients. Differentially expressed genes identified in our study (MYC, FOSL1, EGR1, IL33, LGR5 and FOXQ1) may be used to identify other new molecular targets for chemoprevention of SSLs.","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"214 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590035","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