Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.
Pharmacogenet Genomics
; 34(4): 126-129, 2024 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-38359166
ABSTRACT
Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P â
>â
0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P â
=â
0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Musculoskeletal Diseases
/
Intracellular Signaling Peptides and Proteins
/
Aromatase Inhibitors
/
Pharmacogenomic Variants
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Patient_preference
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Pharmacogenet Genomics
Journal subject:
FARMACOLOGIA
/
GENETICA MEDICA
Year:
2024
Document type:
Article