Scholarlink

Purpose <p>To investigate the joint impacts of genetic and non-genetic factors on breast cancer (BC) subtypes among Chinese females, and to investigate the performance of optimized subtype-specific polygenic risk scores (PRS) with less single nucleotide polymorphisms (SNPs).</p> Methods <p>A total of 6,916 BC cases and 5,653 controls were used to assess the independent and joint impacts of PRS and non-genetic established risk score (ERS) on risks of overall and subtype-specific BC. The PRS were optimized by excluding low-penetrance SNPs until comparable area under receiver-operator-curve (AUCs) achieved.</p> Results <p>For the preliminary PRS with 21 Chinese BC-specific SNPs, the odds ratio (OR) of overall BC for the top decile compared to bottom decile (top-to-bottom decile) of PRS was 4.21 (95%CI: 3.47–5.10), and the OR per decile of PRS was 1.15 (95% CI: 1.13–1.16). For luminal A, luminal B, HER-2 enriched, and basal-like BC, the ORs for top-to-bottom decile were 4.58, 4.37, 3.08 and 2.90, respectively. After integrating four BC subtypes into two subtypes, relatively higher OR for top-to-bottom decile was observed for luminal BC than non-luminal BC (4.54 vs. 3.02), and a similar trend was for OR per decile (1.15 vs. 1.11). The optimized 13-SNP-PRS can achieve comparable performance of 21-SNP-PRS for luminal BC. After incorporating PRS into risk prediction of luminal BC, the AUC increased from 0.673 to 0.697, and the joint OR of PRS and ERS was 12.46(95%CI: 9.38–16.56). Similar performances of PRS were validated in UK biobank.</p> Conclusion <p>PRS can well identify Chinese women at high-risk of BC, especially for luminal BC, and should be incorporated into risk-stratified BC intervention.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Joint impacts of genetic and non-genetic risk scores on risks of different subtypes of breast cancer among Chinese females

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月20日

查看全文
  • Zhipeng Wang,
  • Yunmeng Zhang,
  • Huan Wang,
  • Zhangyan Lyu,
  • Hongji Dai,
  • Yanrui Zhao,
  • Peifang Liu,
  • Ying Zhu,
  • Fangfang Song,
  • Yubei Huang,
  • Fengju Song,
  • Kexin Chen

摘要

Purpose

To investigate the joint impacts of genetic and non-genetic factors on breast cancer (BC) subtypes among Chinese females, and to investigate the performance of optimized subtype-specific polygenic risk scores (PRS) with less single nucleotide polymorphisms (SNPs).

Methods

A total of 6,916 BC cases and 5,653 controls were used to assess the independent and joint impacts of PRS and non-genetic established risk score (ERS) on risks of overall and subtype-specific BC. The PRS were optimized by excluding low-penetrance SNPs until comparable area under receiver-operator-curve (AUCs) achieved.

Results

For the preliminary PRS with 21 Chinese BC-specific SNPs, the odds ratio (OR) of overall BC for the top decile compared to bottom decile (top-to-bottom decile) of PRS was 4.21 (95%CI: 3.47–5.10), and the OR per decile of PRS was 1.15 (95% CI: 1.13–1.16). For luminal A, luminal B, HER-2 enriched, and basal-like BC, the ORs for top-to-bottom decile were 4.58, 4.37, 3.08 and 2.90, respectively. After integrating four BC subtypes into two subtypes, relatively higher OR for top-to-bottom decile was observed for luminal BC than non-luminal BC (4.54 vs. 3.02), and a similar trend was for OR per decile (1.15 vs. 1.11). The optimized 13-SNP-PRS can achieve comparable performance of 21-SNP-PRS for luminal BC. After incorporating PRS into risk prediction of luminal BC, the AUC increased from 0.673 to 0.697, and the joint OR of PRS and ERS was 12.46(95%CI: 9.38–16.56). Similar performances of PRS were validated in UK biobank.

Conclusion

PRS can well identify Chinese women at high-risk of BC, especially for luminal BC, and should be incorporated into risk-stratified BC intervention.