Endocrine-related cancer最新文献_第2页

Paraganglioma and phaeochromocytoma: a review of current guidelines and new diagnostic and therapeutic approaches. 副神经节瘤和嗜铬细胞瘤：当前指南、新诊断和治疗方法综述。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0310

Ruth T Casey, Charlotte Lussey-Lepoutre

引用次数: 0

Investigating the clinical utility of plasma succinate with insights from an Sdhb-deficient murine model. 研究血浆琥珀酸盐在Sdhb缺陷小鼠模型中的临床应用。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0323

Yasemin C Cole, Ifat Abramovich, Jonatan Fernandez-Garcia, France Docquier, James MacFarlane, Xia Xu, Thorkell Andresson, Iris Indig, Herui Wang, Anagha Krishnan, Shuran Chen, Ben Challis, Eyal Gottlieb, Zhengping Zhuang, Eamonn R Maher, Ruth T Casey

{"title":"Investigating the clinical utility of plasma succinate with insights from an Sdhb-deficient murine model.","authors":"Yasemin C Cole, Ifat Abramovich, Jonatan Fernandez-Garcia, France Docquier, James MacFarlane, Xia Xu, Thorkell Andresson, Iris Indig, Herui Wang, Anagha Krishnan, Shuran Chen, Ben Challis, Eyal Gottlieb, Zhengping Zhuang, Eamonn R Maher, Ruth T Casey","doi":"10.1530/ERC-26-0323","DOIUrl":"10.1530/ERC-26-0323","url":null,"abstract":"The succinate dehydrogenase (SDH) enzyme, composed of four subunits (A-D), has a key role in the Krebs cycle and oxidative phosphorylation. Germline pathogenic variants (GPVs) in the genes encoding the four subunits of the succinate dehydrogenase (SDH) enzyme (SDHA/SDHB/SDHC/SDHD), collectively known as SDHx, are recognized as a paradigm for the role of disordered metabolism in oncogenesis as GPVs in SDHx lead to a truncated citric acid cycle due to reduced or absent function of the SDH enzyme and accumulation of the oncometabolite succinate. GPVs in SDHx are the most common cause of hereditary PPGL and are associated with a higher risk of malignant PPGL and predispose to other tumors including renal cell carcinoma, gastrointestinal stromal tumors (GIST), and pituitary adenomas. Utilizing the linkage of SDHx to metabolic dysfunction, we performed prospective plasma metabolomics and identified succinate as a biomarker for early diagnosis of an underlying SDHx variant. Succinate reflected SDHx deficiency in individuals with germline predisposition and a small number of patients with somatic SDHx deficiency, and succinate levels correlated with tumor burden. Longitudinal sampling of patients illustrated that serial succinate measurements might be used as a biomarker for disease surveillance. These findings were validated by tissue analysis in a mouse model of Sdhb deficiency, where elevated succinate was observed in adrenal glands. While circulating plasma levels did not mirror the human cohort, this discrepancy suggests specific cellular thresholds for succinate or SDHx deficiency in adrenal gland tissue and highlights species-specific metabolic regulation.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

COL4A3 promotes invasion and acts as a biomarker in pituitary neuroendocrine tumor. COL4A3促进垂体神经内分泌肿瘤侵袭并作为生物标志物。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0184

Jie Liu, Zhimin Li, Kan Deng, Yuan Zhang, Yue Hu, Yuejia Li, Ming Feng, Bing Xing, Wei Lian, Xinjie Bao, Yong Yao, Yongning Li, Jun Gao

{"title":"COL4A3 promotes invasion and acts as a biomarker in pituitary neuroendocrine tumor.","authors":"Jie Liu, Zhimin Li, Kan Deng, Yuan Zhang, Yue Hu, Yuejia Li, Ming Feng, Bing Xing, Wei Lian, Xinjie Bao, Yong Yao, Yongning Li, Jun Gao","doi":"10.1530/ERC-26-0184","DOIUrl":"10.1530/ERC-26-0184","url":null,"abstract":"Pituitary neuroendocrine tumors (PitNETs) present significant clinical challenges due to unpredictable invasive behavior and lack of reliable molecular predictors. While the extracellular matrix (ECM), particularly type IV collagen, has emerged as a critical mediator of tumor progression, its mechanistic role in PitNETs remains unclear. Through transcriptomic profiling of patient-derived PitNETs, functional assays in GH3 pituitary tumor cells, and orthotopic allograft models, we identified collagen type IV alpha 3 chain (COL4A3) as a key promoter of tumor invasion. Western blotting and flow cytometry revealed that COL4A3 was markedly upregulated in invasive PitNETs and promoted tumor cell proliferation, invasion, and survival both in vitro and in vivo. Mechanistically, COL4A3 knockdown reduced total FAK, PI3K, and AKT protein levels and altered ERK signaling, suggesting a possible link between COL4A3 and this pathway in promoting invasion, suppressing apoptosis, and driving cell cycle progression. Interestingly, serum COL4A3 levels were paradoxically lower in patients with invasive tumors, suggesting complex ECM remodeling dynamics during invasion that may reflect increased matrix degradation or altered systemic release patterns. These findings establish COL4A3 as a potential regulator of PitNET aggressiveness with dual utility as both a therapeutic target and a potential serum biomarker, offering new molecular insights into ECM-mediated tumor progression and opening avenues for precision diagnostics and treatment strategies.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of a GLP-1 agonist and antidiabetic therapies on pheochromocytoma/paraganglioma growth. GLP-1激动剂和抗糖尿病治疗对嗜铬细胞瘤/副神经节瘤生长的影响。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0283

Katharina Wang, Priska Stempfle, Julia Hamati, Alessa Fischer, Umberto Maccio, Achim Weber, Mercedes Robledo, Julian Maurer, Lea Peischer, Astrid Reul, Elena Kuzmenko, Alexander Huber, Diana Vetter, Jose Oberholzer, Nicole Reisch, Petra Zimmermann, Thomas Knösel, Matthias K Auer, Christian Lottspeich, Felix Beuschlein, Constanze Hantel, Ashley B Grossman, Karel Pacak, Kathrin Zitzmann, Christoph J Auernhammer, Svenja Nölting

{"title":"Effects of a GLP-1 agonist and antidiabetic therapies on pheochromocytoma/paraganglioma growth.","authors":"Katharina Wang, Priska Stempfle, Julia Hamati, Alessa Fischer, Umberto Maccio, Achim Weber, Mercedes Robledo, Julian Maurer, Lea Peischer, Astrid Reul, Elena Kuzmenko, Alexander Huber, Diana Vetter, Jose Oberholzer, Nicole Reisch, Petra Zimmermann, Thomas Knösel, Matthias K Auer, Christian Lottspeich, Felix Beuschlein, Constanze Hantel, Ashley B Grossman, Karel Pacak, Kathrin Zitzmann, Christoph J Auernhammer, Svenja Nölting","doi":"10.1530/ERC-26-0283","DOIUrl":"10.1530/ERC-26-0283","url":null,"abstract":"A high proportion of patients with pheochromocytomas and paragangliomas (PPGLs) show glycemic dysregulation. However, studies on the effects of antidiabetic drugs on PPGL tumor growth are still lacking. We evaluated the effects of glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide, metformin, and insulin on fresh patient-derived PPGL primary cultures (n = 54), including 8 cluster 1 tumors and 18 cluster 2/3 tumors (n = 4 tumors with RET pathogenic variants (PVs)). We correlated the primary culture data with clinical data from 67 patients enrolled in the prospective clinical trial PROSPHEO (NCT03344016). We found cluster-dependent effects of semaglutide in patient primary cultures, with significant antitumor effects in cluster 1 PPGLs. Interestingly, we found tumor-promoting effects of high-dose semaglutide in three PPGLs with germline RET PVs (MEN2 syndrome), but not in a PPGL with a somatic RET PV. Metformin displayed overall antitumor effects, whereas insulin showed individual tumor-promoting effects in the patient primary cultures. Consistently, clinical data confirmed larger median tumor sizes in PPGL patients receiving insulin therapy compared with those receiving metformin/GLP-1RA therapy or those without antidiabetic therapy. Overall, we provide novel data on the effects of antidiabetic drugs on PPGL tumor growth, including significant antitumor effects of the GLP-1RA semaglutide in cluster 1 PPGLs and tumor-promoting effects in patients with MEN2 syndrome. Further confirmation of our data in prospective clinical studies is required.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

18F-CETO in adrenocortical carcinoma: first clinical-translational study of an adrenocortical-targeting PET tracer. 18F-CETO在肾上腺皮质癌中的作用：一种靶向肾上腺皮质的PET示踪剂的首次临床转化研究。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0314

Adam Edholm, Liang Zhang, James MacFarlane, Tobias Åkerström, Russell Senanayake, Staffan Welin, Agnes Hegedus, Heok K Cheow, Ieva Lase, Peter Stålberg, Azita Monazzam, Daniel Gillett, Luigi Aloj, Per Hellman, Hanna Wargelius, John A Tadross, Gunnar Antoni, Franklin Aigbirhio, Britt Skogseid, Mark Gurnell, Samuel Backman, Anders Sundin, Ruth T Casey, Joakim Crona

{"title":"18F-CETO in adrenocortical carcinoma: first clinical-translational study of an adrenocortical-targeting PET tracer.","authors":"Adam Edholm, Liang Zhang, James MacFarlane, Tobias Åkerström, Russell Senanayake, Staffan Welin, Agnes Hegedus, Heok K Cheow, Ieva Lase, Peter Stålberg, Azita Monazzam, Daniel Gillett, Luigi Aloj, Per Hellman, Hanna Wargelius, John A Tadross, Gunnar Antoni, Franklin Aigbirhio, Britt Skogseid, Mark Gurnell, Samuel Backman, Anders Sundin, Ruth T Casey, Joakim Crona","doi":"10.1530/ERC-26-0314","DOIUrl":"10.1530/ERC-26-0314","url":null,"abstract":"The adrenocortical-specific PET tracer [11C]metomidate (11C-MTO) shows high diagnostic accuracy in adrenocortical carcinoma (ACC), but complex radiochemistry and short half-life limit clinical implementation. The novel tracer para-chloro-2-[18F]fluoroethyletomidate (18F-CETO) may enable broader use. In this bicentric study, 20 ACC patients underwent PET/CT with 18F-CETO and [18F]fluoro-2-deoxy-D-glucose (18F-FDG), with 235 lesions identified. 18F-CETO detected more lesions than 18F-FDG at initial staging in 5/13 patients, whereas fewer lesions were detected at re-staging in 5/7 patients (P = 0.002). A further 70 patients with 18F-CETO or 11C-MTO-PET/CT and an anatomical imaging reference were used to explore the utility of adrenocortical imaging. Three adrenocortical imaging phenotypes were defined: homogeneous-high (n = 71), homogeneous-low (n = 11), and heterogeneous (n = 8), which showed differences in overall survival in exploratory analyses. Tumors were characterized by RNA sequencing and immunohistochemistry showing correlation between tracer-uptake to CYP11B1 expression and adrenocortical differentiation. These findings suggest a potential role for 18F-CETO in ACC phenotyping and initial staging.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into shared genetic architecture linking thyroid function and cancer. 对连接甲状腺功能和癌症的共享遗传结构的见解。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-26-0197

Weiming Wu, Wenxin Zhang, Juncen Guo, Wendi Cheng, Mengge Liu, Lin Li, Huawei Cai, Lisha Jiang

{"title":"Insights into shared genetic architecture linking thyroid function and cancer.","authors":"Weiming Wu, Wenxin Zhang, Juncen Guo, Wendi Cheng, Mengge Liu, Lin Li, Huawei Cai, Lisha Jiang","doi":"10.1530/ERC-26-0197","DOIUrl":"10.1530/ERC-26-0197","url":null,"abstract":"Growing evidence suggests a complex interplay between thyroid function and various cancers, yet their shared genetic basis and underlying mechanisms remain unclear. This study leveraged large-scale genome-wide association study (GWAS) summary statistics for four thyroid function and seven cancer traits. We systematically investigated the shared genetic architecture between thyroid function and cancer susceptibility at global, locus, gene, and functional levels. Genome-wide genetic correlations and overlap were first assessed at the global level. Pleiotropic analysis under composite null hypothesis (PLACO) was then applied to identify specific shared loci between thyroid function and cancers. At the gene level, shared genes were prioritized using expression-trait association and colocalization analyses. Finally, functional enrichment and druggability analyses were conducted to explore the biological relevance of shared genes and their potential as therapeutic targets. We observed widespread global genetic overlap between thyroid function and cancers. At the locus level, PLACO identified 489 loci across 28 thyroid function-cancer pairs, including 79 novel loci for both traits. Colocalization and local genetic correlation analyses further highlighted 22 key loci. At the gene level, 81 shared genes were prioritized, with NUCKS1, SLC41A1, SIVA1, CTA-398F10.2, and INSR showing consistent evidence in both expression-trait association and colocalization analyses. Moreover, druggability analyses predicted 1,064 potential interactions, revealing promising targets for drug repurposing. Our integrative analysis uncovers extensive shared genetic architecture between thyroid function and multiple cancers, highlighting key loci and prioritized shared genes and providing mechanistic insights into the genetic links between thyroid function and cancer susceptibility.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TCF4-driven cathepsin S promotes papillary thyroid carcinoma via PI3K/AKT/mTOR. tcf4驱动的组织蛋白酶S通过PI3K/AKT/mTOR促进甲状腺乳头状癌。

IF 4.6

Endocrine-related cancer Pub Date : 2026-10-01 DOI: 10.1530/ERC-25-0517

Xinyi Zhang, Shengyi Zhou, Shuyi Zhang, Yizhou Sun, Wei Yuan, Hongjie Xu, Chengzhi Zhang, Andong Xu, Linsen Zhou, Guangjun Zhou

{"title":"TCF4-driven cathepsin S promotes papillary thyroid carcinoma via PI3K/AKT/mTOR.","authors":"Xinyi Zhang, Shengyi Zhou, Shuyi Zhang, Yizhou Sun, Wei Yuan, Hongjie Xu, Chengzhi Zhang, Andong Xu, Linsen Zhou, Guangjun Zhou","doi":"10.1530/ERC-25-0517","DOIUrl":"10.1530/ERC-25-0517","url":null,"abstract":"Papillary thyroid carcinoma (PTC) usually has a good prognosis, but lacks effective molecular biomarkers and therapeutic targets. However, a subset of patients develops lymph node metastasis, radioiodine resistance, and recurrence. Cathepsin S (CTSS), a lysosomal cysteine protease, has been implicated in several malignancies, yet its role and regulation in PTC remain unclear. We integrated GEO and TCGA-THCA datasets with eQTL-based genetic instrument analyses to screen PTC-related genes and evaluate their association with clinicopathological features and DFS. CTSS expression was examined in clinical tissues and cell lines by immunohistochemistry, RT-qPCR, and western blotting. Gain- and loss-of-function models were used to assess the effects of CTSS on PTC cell proliferation, colony formation, migration, apoptosis, and nude-mouse tumor growth. RNA-seq and TCGA pathway-score correlation analysis were used to explore downstream pathways, and transcriptional regulation was investigated by in silico prediction, ChIP-qPCR, and dual-luciferase assays. CTSS emerged as a candidate gene associated with PTC occurrence, lymph node metastasis, and shorter DFS. CTSS was markedly upregulated in PTC tissues and cell lines. Functionally, CTSS knockdown suppressed proliferation and migration/invasion and promoted apoptosis, whereas CTSS overexpression enhanced malignant phenotypes in the examined PTC cell models. CTSS expression was associated with activation of the PI3K/AKT/mTOR pathway, and CTSS inhibition attenuated pathway activation and tumor growth. TCF4 bound the CTSS promoter, increased CTSS transcription, and TCF4 knockdown reduced CTSS expression and PI3K/AKT/mTOR pathway activity. These findings suggest that CTSS promotes malignant phenotypes in PTC and is associated with PI3K/AKT/mTOR activation, while TCF4 may contribute to CTSS transcriptional regulation.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expert consensus on the reporting and clinical follow up of individuals with incidentally discovered germline RET variants in the UK. 在英国偶然发现生殖系RET变异个体的报告和临床随访指南。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0194

Helen Hanson, Katie Snape, Renuka P Dias, Soo-Mi Park, M Guftar Shaikh, Tom R Kurzawinski, Louise Izatt, Kashyap A Patel, Márta Korbonits, Ruth T Casey

{"title":"Expert consensus on the reporting and clinical follow up of individuals with incidentally discovered germline RET variants in the UK.","authors":"Helen Hanson, Katie Snape, Renuka P Dias, Soo-Mi Park, M Guftar Shaikh, Tom R Kurzawinski, Louise Izatt, Kashyap A Patel, Márta Korbonits, Ruth T Casey","doi":"10.1530/ERC-26-0194","DOIUrl":"10.1530/ERC-26-0194","url":null,"abstract":"Incidentally discovered pathogenic germline genetic variants refer to the finding of a pathogenic variant in a gene that is unrelated to the reason for the initial test and is not actively sought. Our clinical understanding of the risk of developing a particular medical condition and the required clinical action for a specific pathogenic gene variant is predominantly based on knowledge and information acquired from cases ascertained through a 'phenotype-first approach' rather than in clinically unselected individuals. Therefore, a modified approach is required for incidentally discovered gene variants. Data from large UK and US population-based cohorts have demonstrated that RET variants classified as moderate-risk RET variants as per the American Thyroid Association (ATA) classification have a low penetrance for medullary thyroid cancer and other RET-related conditions (e.g. phaeochromocytoma) and are not associated with excess mortality when identified incidentally in clinically unselected adult individuals. Here, we provide guidance based on multidisciplinary expert consensus opinion for the reporting and subsequent clinical surveillance and management of patients with incidentally discovered RET gene variants in the UK.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxisome proliferator-activated receptor γ inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner. 过氧化物酶体增殖物激活受体γ通过上调p21Cip1/WAF1基因以sp1依赖的方式抑制滤泡性和间变性甲状腺癌细胞的生长。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-07-0272

D Bonofiglio, H Qi, S Gabriele, S Catalano, S Aquila, M Belmonte, S Ando

引用次数: 0

Genetically determined ABO blood group, secretor status, Lewis antigens, and panNEN risk. 基因决定ABO血型，分泌状态，路易斯抗原，和panNENs风险。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0286

Samuel O Antwi, Erin E Carlson, Kari G Rabe, Teja Koganti, William R Bamlet, Thorvardur R Halfdanarson, Robert R McWilliams, Kirk J Wangensteen, Ann L Oberg

{"title":"Genetically determined ABO blood group, secretor status, Lewis antigens, and panNEN risk.","authors":"Samuel O Antwi, Erin E Carlson, Kari G Rabe, Teja Koganti, William R Bamlet, Thorvardur R Halfdanarson, Robert R McWilliams, Kirk J Wangensteen, Ann L Oberg","doi":"10.1530/ERC-26-0286","DOIUrl":"10.1530/ERC-26-0286","url":null,"abstract":"Pancreatic neuroendocrine neoplasms (panNENs) are rare endocrine malignancies with poorly defined risk factors, in contrast to the more common pancreatic ductal adenocarcinoma (PDAC), for which non-O ABO blood group is a well-established susceptibility marker. To determine whether ABO and related glycosylation markers associated with PDAC risk extend to panNENs, we conducted a case-control study of 1,059 pathologically confirmed panNEN cases from the Mayo Clinic Biospecimen Resource for Pancreas Research and 33,018 cancer-free controls from the Mayo ClinicBiobank. Using germline genotype data, we inferred ABO blood group, FUT2-defined secretor status, and FUT3-defined Lewis antigen phenotypes and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression adjusted for age, sex, and ancestry principal components. ABO blood group was not associated with panNEN risk: compared with blood group O, the OR for non-O was 0.98 (95% CI: 0.87-1.11), with similarly null findings for blood groups A, B, and AB individually. Secretor status (OR = 0.98, 95% CI: 0.84-1.14) and Lewis-positive phenotypes (OR = 0.91, 95% CI: 0.75-1.13) were also not associated with risk, and no interactions were observed between blood group and secretor status or Lewis antigen phenotypes. Given our high statistical power to detect previously reported PDAC effect sizes for non-O blood group, these null findings are informative, indicating that the ABO-linked glycosylation, inflammatory, and host-microbe interaction pathways implicated in PDAC are unlikely to be major determinants of panNEN susceptibility. This study therefore sharpens the etiologic distinction between pancreatic exocrine and neuroendocrine cancers, redirecting panNEN research beyond PDAC paradigms toward alternative mechanisms of endocrine tumorigenesis.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0