Pub Date : 2024-04-04DOI: 10.1007/s10689-024-00372-5
Michelle F. Jacobs, Elena M. Stoffel
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.
{"title":"Genetic and other risk factors for pancreatic ductal adenocarcinoma (PDAC)","authors":"Michelle F. Jacobs, Elena M. Stoffel","doi":"10.1007/s10689-024-00372-5","DOIUrl":"https://doi.org/10.1007/s10689-024-00372-5","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590020","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}
Pub Date : 2024-04-04DOI: 10.1007/s10689-024-00380-5
Kasper A. Overbeek, Djuna L. Cahen, Marco J. Bruno
Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals.
{"title":"The role of endoscopic ultrasound in the detection of pancreatic lesions in high-risk individuals","authors":"Kasper A. Overbeek, Djuna L. Cahen, Marco J. Bruno","doi":"10.1007/s10689-024-00380-5","DOIUrl":"https://doi.org/10.1007/s10689-024-00380-5","url":null,"abstract":"<p>Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590132","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}
Pub Date : 2024-03-16DOI: 10.1007/s10689-024-00362-7
Anne Marie Jelsig, John Gásdal Karstensen, Thomas V Overeem Hansen
Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.
{"title":"Progress report: Peutz-Jeghers syndrome.","authors":"Anne Marie Jelsig, John Gásdal Karstensen, Thomas V Overeem Hansen","doi":"10.1007/s10689-024-00362-7","DOIUrl":"https://doi.org/10.1007/s10689-024-00362-7","url":null,"abstract":"<p><p>Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140104","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}
Pub Date : 2024-03-13DOI: 10.1007/s10689-024-00358-3
Hans F A Vasen
{"title":"In Memoriam: Steffen Bülow (1943-2023).","authors":"Hans F A Vasen","doi":"10.1007/s10689-024-00358-3","DOIUrl":"https://doi.org/10.1007/s10689-024-00358-3","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119229","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}
Pub Date : 2024-03-01Epub Date: 2024-01-11DOI: 10.1007/s10689-023-00353-0
Douglas Tjandra, Alex Boussioutas
Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.
李-弗劳米尼综合征(LFS)是由 TP53 的种系致病变异引起的,容易导致多种年轻发病的恶性肿瘤,尤其是肉瘤、乳腺癌和脑癌。最近,人们认识到胃腺癌的风险增加,但对上消化道内窥镜的监测还不清楚。我们对65名LFS患者进行了回顾性研究,其中53.8%的患者接受了内镜检查,结果发现4名患者(6.2%)患有胃食管交界处(GEJ)腺癌。其中两例是在无症状筛查中发现的,属于早期病变。没有病例有胃肠道恶性肿瘤家族史。通过审查癌症基因组图谱计划(The Cancer Genome Atlas Program)的基因组数据,76.4%的散发性食管腺癌携带体细胞TP53致病变异,而非心源性胃癌的这一比例为39.9%。在种系和散发性病例中观察到的这种相似模式值得进一步研究。我们建议对所有LFS患者进行上消化道内镜检查,重点是对GEJ进行适当的监测。
{"title":"Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours.","authors":"Douglas Tjandra, Alex Boussioutas","doi":"10.1007/s10689-023-00353-0","DOIUrl":"10.1007/s10689-023-00353-0","url":null,"abstract":"<p><p>Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416779","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}
Pub Date : 2024-03-01Epub Date: 2023-11-14DOI: 10.1007/s10689-023-00350-3
Dylan Pelletier, Abhijit Rath, Nelly Sabbaghian, Manuela Pelmus, Catherine Hudon, Karine Jacob, Leora Witowski, Avi Saskin, Christopher D Heinen, William D Foulkes
Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.
{"title":"Functional and phenotypic consequences of an unusual inversion in MSH2.","authors":"Dylan Pelletier, Abhijit Rath, Nelly Sabbaghian, Manuela Pelmus, Catherine Hudon, Karine Jacob, Leora Witowski, Avi Saskin, Christopher D Heinen, William D Foulkes","doi":"10.1007/s10689-023-00350-3","DOIUrl":"10.1007/s10689-023-00350-3","url":null,"abstract":"<p><p>Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153425","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}
Pub Date : 2024-03-01Epub Date: 2024-01-31DOI: 10.1007/s10689-023-00354-z
Marya Pulaski, Michaela Dungan, Marina Weber, Gillain Constantino, Bryson W Katona
Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsied individuals with LS had GIM and/or HP (5.5% GIM, 3.6% HP). Biopsies of the gastric body did not increase rates of GIM/HP identification compared to antral biopsies alone. GIM was detected on subsequent surveillance in 2.2% of individuals without prior GIM, which may represent either newly developed GIM or GIM that was missed on a prior upper endoscopy due to sampling error. These findings support inclusion of at least baseline gastric antrum biopsies as a routine component of all standard surveillance upper endoscopies performed in LS.
{"title":"Low prevalence of gastric intestinal metaplasia and Helicobacter pylori on surveillance upper endoscopy in Lynch syndrome.","authors":"Marya Pulaski, Michaela Dungan, Marina Weber, Gillain Constantino, Bryson W Katona","doi":"10.1007/s10689-023-00354-z","DOIUrl":"10.1007/s10689-023-00354-z","url":null,"abstract":"<p><p>Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsied individuals with LS had GIM and/or HP (5.5% GIM, 3.6% HP). Biopsies of the gastric body did not increase rates of GIM/HP identification compared to antral biopsies alone. GIM was detected on subsequent surveillance in 2.2% of individuals without prior GIM, which may represent either newly developed GIM or GIM that was missed on a prior upper endoscopy due to sampling error. These findings support inclusion of at least baseline gastric antrum biopsies as a routine component of all standard surveillance upper endoscopies performed in LS.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641986","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}
Pub Date : 2024-03-01Epub Date: 2024-01-25DOI: 10.1007/s10689-023-00355-y
R De Santis, G Cagnoli, B Rinaldi, D Consonni, Beatrice Conti, M Eoli, A Liguori, M Cosentino, G Carrafiello, O Garrone, M Giroda, C Cesaretti, M S Sfondrini, D Gambini, F Natacci
Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.
神经纤维瘤病 1 型(NF1)是一种常染色体显性遗传病,由 NF1 基因中的致病变体导致神经纤维瘤蛋白单倍体缺乏引起。肿瘤易感性长期以来一直与 NF1 相关,近年来有报道称,NF1 女性患者的乳腺癌(BC)发病率增加,存活率降低。由于乳房密度是乳腺癌的另一个已知独立风险因素,本研究旨在评估与普通人群相比,NF1 患者乳房密度的变化情况。我们将 98 名受 NF1 影响的 NF1 妇女的乳房 X 光照片与 300 名健康受试者的乳房 X 光照片进行了比较,以验证乳房密度的差异。乳房 X 光照片由放射科医生使用计算机辅助检测 (CAD) 软件进行独立审查和评分。NF1患者和对照组之间乳腺密度的比较通过Chi-squared检验和多变量序数逻辑模型进行,并对年龄、体重指数(BMI)、怀孕次数和绝经状态进行了调整。尽管NF1和高纤维腺性乳房是已知的乳腺增生症风险因素,但在本研究中,NF1患者的乳房密度与健康受试者相当。NF1基因致病变体的存在并不影响乳腺密度值。
{"title":"Breast density in NF1 women: a retrospective study.","authors":"R De Santis, G Cagnoli, B Rinaldi, D Consonni, Beatrice Conti, M Eoli, A Liguori, M Cosentino, G Carrafiello, O Garrone, M Giroda, C Cesaretti, M S Sfondrini, D Gambini, F Natacci","doi":"10.1007/s10689-023-00355-y","DOIUrl":"10.1007/s10689-023-00355-y","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546170","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}
Pub Date : 2024-01-27DOI: 10.1007/s10689-024-00357-4
Sabine Biermann, Michael Knapp, Peter Wieacker, Stefan Aretz, Verena Steinke-Lange
Lynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort. There was no difference between the age of menopause in patients compared to controls and no evidence for a higher risk of POF in LS patients. However, around one third (35%) of the probands have already had premenopausal cancer and mostly cancer-related treatment affecting fertility before the age of 45 years. Therefore, childbearing time might still be limited in these patients, especially due to the premenopausal cancer risk. LS patients should be informed in time about the elevated premenopausal cancer risks and the possible impact on family planning. This is particularly relevant since the average childbearing age has increased during the last decades.
林奇综合征(LS;HNPCC)患者携带错配修复(MMR)基因中的杂合致病性种系变异,而这些基因在减数分裂过程中也发挥着重要作用。因此,我们推测LS可能与卵巢早衰(POF)或更年期提前的高风险有关。研究人员收集了167名LS女性患者的妇科病史、癌症诊断和治疗数据,并与人群对照组进行了比较。与对照组相比,患者的绝经年龄没有差异,也没有证据表明LS患者患POF的风险更高。不过,约有三分之一(35%)的受试者在45岁之前就已罹患绝经前癌症,而且大多接受了影响生育能力的癌症相关治疗。因此,这些患者的生育时间可能仍然有限,特别是由于绝经前癌症风险。应及时告知 LS 患者绝经前癌症风险的升高以及对计划生育可能产生的影响。这一点尤为重要,因为在过去几十年中,平均生育年龄有所提高。
{"title":"High amount of fertility reducing tumors and procedures, but no evidence for premature ovarian failure in female Lynch syndrome patients.","authors":"Sabine Biermann, Michael Knapp, Peter Wieacker, Stefan Aretz, Verena Steinke-Lange","doi":"10.1007/s10689-024-00357-4","DOIUrl":"https://doi.org/10.1007/s10689-024-00357-4","url":null,"abstract":"<p><p>Lynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort. There was no difference between the age of menopause in patients compared to controls and no evidence for a higher risk of POF in LS patients. However, around one third (35%) of the probands have already had premenopausal cancer and mostly cancer-related treatment affecting fertility before the age of 45 years. Therefore, childbearing time might still be limited in these patients, especially due to the premenopausal cancer risk. LS patients should be informed in time about the elevated premenopausal cancer risks and the possible impact on family planning. This is particularly relevant since the average childbearing age has increased during the last decades.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570136","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}