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Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing
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Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing
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Journal Article
Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing
2024
Overview
Persistent taxane-induced peripheral neuropathy (TIPN) is highly prevalent among early-stage breast cancer survivors (ESBCS) and has detrimental effect on quality of life. We leveraged logistic regression models to develop and validate polygenic prediction models to estimate the risk of persistent PN symptoms in a training cohort and validation cohort taking clinical risk factors into account. Based on 337 whole-exome sequenced ESBCS two of five prediction models for individual PN symptoms obtained AUC results above 60% when validated. Using the model for
numbness in feet
(35 SNVs) in the test cohort, 73% survivors were correctly predicted. For
tingling in feet
(55 SNVs) 70% were correctly predicted. Both models included SNVs from the
ADAMTS20, APT6V0A2, CCDC88C, CYP2C8, EPHA5, NR1H3, PSKH2/APTV0D2
, and
SCN10A
genes. For
cramps in feet
,
difficulty climbing stairs
and
difficulty opening a jar
the validation was unsuccessful. Polygenic prediction models including clinical risk factors can estimate the risk of persistent taxane-induced
numbness in feet
and
tingling in feet
in ESBCS.
