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Purpose <p>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> Methods <p>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> Results <p>The median age at diagnosis was 69&#xa0;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> Conclusions <p>Our results suggest that SDC4 may play a role in the initiation and early progression of breast cancer.</p>

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Higher pre-diagnostic serum syndecan-4 levels are associated with increased breast cancer risk: a case-cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月22日

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  • 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

摘要

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.