Endre Gabrielsen, Tom Wilsgaard, Hanne Frydenberg, Trygve Lofterød, Stig Manfred Dalen, Elin Mortensen, Marit D Solbu, Hawa Nalwoga, Lars A Akslen, Egil S Blix, Hege S Haugnes
{"title":"较高的诊断前血清syndecan-4水平与乳腺癌风险增加相关：一项病例队列研究","authors":"Endre Gabrielsen, Tom Wilsgaard, Hanne Frydenberg, Trygve Lofterød, Stig Manfred Dalen, Elin Mortensen, Marit D Solbu, Hawa Nalwoga, Lars A Akslen, Egil S Blix, Hege S Haugnes","doi":"10.1007/s10549-025-07786-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Syndecans are transmembrane proteins involved in inflammation and signaling pathways. Their potential role as pre-diagnostic biomarkers for breast cancer risk remains unexplored. This study aimed to investigate whether pre-diagnostic serum syndecan levels are associated with breast cancer risk in a population-based cohort.</p><p><strong>Methods: </strong>We conducted a case-cohort study nested within the Tromsø Study (Norway), including women who participated in the fifth survey (2001). Women with incident breast cancer (cases, n = 158) through 2022 were identified, with a random sub-cohort of 708 women. Serum levels of syndecan-1 (SDC1) and syndecan-4 (SDC4) were measured using ELISA on frozen serum samples obtained in 2001. All participants were stratified into quartiles (Q1-Q4) based on pre-diagnostic levels. Cox proportional hazards regression models assessed associations between serum syndecan levels and breast cancer risk.</p><p><strong>Results: </strong>The median age at diagnosis was 69 years for cases, and 83.3% of tumors were hormone receptor-positive (HR +). Women with higher serum SDC4 (Q2-Q4) levels had approximately a twofold increased risk of breast cancer compared to women in Q1. We observed a nearly threefold increased risk for the HR + subtype. In postmenopausal women, HRs for HR + breast cancer in Q2, Q3, and Q4 were 3.81 (95% CI: 1.57-9.23), 3.43 (95% CI: 1.41-8.40), and 3.54 (95% CI: 1.45-8.65), respectively, all relative to Q1 of SDC4. No associations were observed between SDC1 levels and breast cancer risk.</p><p><strong>Conclusions: </strong>Our results suggest that SDC4 may play a role in the initiation and early progression of breast cancer.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"365-375"},"PeriodicalIF":3.0000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397127/pdf/","citationCount":"0","resultStr":"{\"title\":\"Higher pre-diagnostic serum syndecan-4 levels are associated with increased breast cancer risk: a case-cohort study.\",\"authors\":\"Endre Gabrielsen, Tom Wilsgaard, Hanne Frydenberg, Trygve Lofterød, Stig Manfred Dalen, Elin Mortensen, Marit D Solbu, Hawa Nalwoga, Lars A Akslen, Egil S Blix, Hege S Haugnes\",\"doi\":\"10.1007/s10549-025-07786-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Syndecans are transmembrane proteins involved in inflammation and signaling pathways. Their potential role as pre-diagnostic biomarkers for breast cancer risk remains unexplored. This study aimed to investigate whether pre-diagnostic serum syndecan levels are associated with breast cancer risk in a population-based cohort.</p><p><strong>Methods: </strong>We conducted a case-cohort study nested within the Tromsø Study (Norway), including women who participated in the fifth survey (2001). Women with incident breast cancer (cases, n = 158) through 2022 were identified, with a random sub-cohort of 708 women. Serum levels of syndecan-1 (SDC1) and syndecan-4 (SDC4) were measured using ELISA on frozen serum samples obtained in 2001. All participants were stratified into quartiles (Q1-Q4) based on pre-diagnostic levels. Cox proportional hazards regression models assessed associations between serum syndecan levels and breast cancer risk.</p><p><strong>Results: </strong>The median age at diagnosis was 69 years for cases, and 83.3% of tumors were hormone receptor-positive (HR +). Women with higher serum SDC4 (Q2-Q4) levels had approximately a twofold increased risk of breast cancer compared to women in Q1. We observed a nearly threefold increased risk for the HR + subtype. In postmenopausal women, HRs for HR + breast cancer in Q2, Q3, and Q4 were 3.81 (95% CI: 1.57-9.23), 3.43 (95% CI: 1.41-8.40), and 3.54 (95% CI: 1.45-8.65), respectively, all relative to Q1 of SDC4. No associations were observed between SDC1 levels and breast cancer risk.</p><p><strong>Conclusions: </strong>Our results suggest that SDC4 may play a role in the initiation and early progression of breast cancer.</p>\",\"PeriodicalId\":9133,\"journal\":{\"name\":\"Breast Cancer Research and Treatment\",\"volume\":\" \",\"pages\":\"365-375\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397127/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research and Treatment\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10549-025-07786-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10549-025-07786-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Higher pre-diagnostic serum syndecan-4 levels are associated with increased breast cancer risk: a case-cohort study.
Purpose: Syndecans are transmembrane proteins involved in inflammation and signaling pathways. Their potential role as pre-diagnostic biomarkers for breast cancer risk remains unexplored. This study aimed to investigate whether pre-diagnostic serum syndecan levels are associated with breast cancer risk in a population-based cohort.
Methods: We conducted a case-cohort study nested within the Tromsø Study (Norway), including women who participated in the fifth survey (2001). Women with incident breast cancer (cases, n = 158) through 2022 were identified, with a random sub-cohort of 708 women. Serum levels of syndecan-1 (SDC1) and syndecan-4 (SDC4) were measured using ELISA on frozen serum samples obtained in 2001. All participants were stratified into quartiles (Q1-Q4) based on pre-diagnostic levels. Cox proportional hazards regression models assessed associations between serum syndecan levels and breast cancer risk.
Results: The median age at diagnosis was 69 years for cases, and 83.3% of tumors were hormone receptor-positive (HR +). Women with higher serum SDC4 (Q2-Q4) levels had approximately a twofold increased risk of breast cancer compared to women in Q1. We observed a nearly threefold increased risk for the HR + subtype. In postmenopausal women, HRs for HR + breast cancer in Q2, Q3, and Q4 were 3.81 (95% CI: 1.57-9.23), 3.43 (95% CI: 1.41-8.40), and 3.54 (95% CI: 1.45-8.65), respectively, all relative to Q1 of SDC4. No associations were observed between SDC1 levels and breast cancer risk.
Conclusions: Our results suggest that SDC4 may play a role in the initiation and early progression of breast cancer.
期刊介绍：
Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.
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