Gabrielsen Endre, Wilsgaard Tom, Frydenberg Hanne, Lofterød Trygve, Dalen Stig Manfred, Mortensen Elin, Solbu Marit D, Nalwoga Hawa, Akslen Lars A, Blix Egil S, Haugnes Hege S
Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037, Tromsø, Norway.
Department of Oncology, University Hospital of North Norway, 9038, Tromsø, Norway.
Breast Cancer Res Treat. 2025 Jul 22. doi: 10.1007/s10549-025-07786-4.
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.
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.
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.
Our results suggest that SDC4 may play a role in the initiation and early progression of breast cancer.
Syndecans是参与炎症和信号通路的跨膜蛋白。它们作为乳腺癌风险的诊断前生物标志物的潜在作用仍未得到探索。本研究旨在调查在一个基于人群的队列中，诊断前血清syndecan水平是否与乳腺癌风险相关。
我们在特罗姆瑟研究（挪威）中进行了一项病例队列研究，纳入了参加第五次调查（2001年）的女性。确定了截至2022年患原发性乳腺癌的女性（病例，n = 158），以及一个由708名女性组成的随机子队列。使用酶联免疫吸附测定法（ELISA）检测2001年采集的冷冻血清样本中syndecan-1（SDC1）和syndecan-4（SDC4）的血清水平。所有参与者根据诊断前水平分为四分位数（Q1-Q4）。Cox比例风险回归模型评估血清syndecan水平与乳腺癌风险之间的关联。
病例的诊断中位年龄为69岁，83.3%的肿瘤为激素受体阳性（HR+）。血清SDC4水平较高（Q2-Q4）的女性患乳腺癌的风险比Q1中的女性增加了约两倍。我们观察到HR+亚型的风险增加了近三倍。在绝经后女性中，Q2、Q3和Q4中HR+乳腺癌的风险比分别为3.81（95%置信区间：1.57-9.23）、3.43（95%置信区间：1.41-8.40）和3.54（95%置信区间：1.45-8.65），均相对于SDC4的Q1。未观察到SDC1水平与乳腺癌风险之间的关联。
我们的结果表明，SDC4可能在乳腺癌的发生和早期进展中起作用。
