Whole-exome sequencing identifies genetic markers for taxane-induced multi-organ adverse effects in breast cancer patients
Abstract
IntroductionTaxanes are standard chemotherapeutic agents for breast cancer, yet their clinical utility is often limited by severe multi-organ adverse drug reactions (ADRs), which show marked inter‐individual variability. MethodsTo investigate the genetic basis of this variability, we performed whole‐exome sequencing (WES) in 203 breast cancer patients receiving taxane‐based chemotherapy and assessed five ADR phenotypes—neutropenia, leukopenia, rash, peripheral neurotoxicity, and gastrointestinal toxicity. Common variants were tested via single‐variant association tests, and rare variants via gene-based burden tests (SKAT‐O).ResultsIn common‐variant analysis, PTGES rs2302821 showed a significant association with neutropenia (joint genotype test P = 5.57 × 10−6; adjusted P = 2.19 × 10−6), with the AC genotype conferring a protective effect (adjusted OR = 0.17, 95% CI: 0.08–0.35). For rash, rare-variant gene‐based analysis nominated GSDMA as a candidate (P = 2.88 × 10−7). GSDMA exhibited skin‐specific expression, and missense variants were exclusively observed in affected cases; however, these results remain exploratory given the limited number of rash cases (n = 12). A common‐variant signal in IL36B was nominally significant in unadjusted analysis but attenuated after covariate adjustment, warranting further validation.DiscussionOur findings identify PTGES rs2302821 as a potential genetic marker for taxane‐induced neutropenia and nominate GSDMA as a preliminary candidate for rash susceptibility, providing a genomic perspective on inter‐individual variability in taxane‐related ADRs.
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BibTeX
@article{liu2026wholeexome,
title = {{Whole-exome sequencing identifies genetic markers for taxane-induced multi-organ adverse effects in breast cancer patients}},
author = {Yamin Liu and Yunxiao Lin and Xueting Xing and Hai Zhang and Yongzhe Tang and Hao Wu and Shengying Qin and Ruizhuo Ouyang and Cong Huai and Xiaoqing Zhang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1917835},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1917835},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Whole-exome sequencing identifies genetic markers for taxane-induced multi-organ adverse effects in breast cancer patients
AU - Yamin Liu
AU - Yunxiao Lin
AU - Xueting Xing
AU - Hai Zhang
AU - Yongzhe Tang
AU - Hao Wu
AU - Shengying Qin
AU - Ruizhuo Ouyang
AU - Cong Huai
AU - Xiaoqing Zhang
PY - 2026
DA - 2026/11/05
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1917835
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1917835
AB - IntroductionTaxanes are standard chemotherapeutic agents for breast cancer, yet their clinical utility is often limited by severe multi-organ adverse drug reactions (ADRs), which show marked inter‐individual variability. MethodsTo investigate the genetic basis of this variability, we performed whole‐exome sequencing (WES) in 203 breast cancer patients receiving taxane‐based chemotherapy and assessed five ADR phenotypes—neutropenia, leukopenia, rash, peripheral neurotoxicity, and gastrointestinal toxicity. Common variants were tested via single‐variant association tests, and rare variants via gene-based burden tests (SKAT‐O).ResultsIn common‐variant analysis, PTGES rs2302821 showed a significant association with neutropenia (joint genotype test P = 5.57 × 10−6; adjusted P = 2.19 × 10−6), with the AC genotype conferring a protective effect (adjusted OR = 0.17, 95% CI: 0.08–0.35). For rash, rare-variant gene‐based analysis nominated GSDMA as a candidate (P = 2.88 × 10−7). GSDMA exhibited skin‐specific expression, and missense variants were exclusively observed in affected cases; however, these results remain exploratory given the limited number of rash cases (n = 12). A common‐variant signal in IL36B was nominally significant in unadjusted analysis but attenuated after covariate adjustment, warranting further validation.DiscussionOur findings identify PTGES rs2302821 as a potential genetic marker for taxane‐induced neutropenia and nominate GSDMA as a preliminary candidate for rash susceptibility, providing a genomic perspective on inter‐individual variability in taxane‐related ADRs.
SN - 1663-9812
ER -