Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse events during aromatase inhibitor treatment for breast cancer.
Jacqueline M DempseyJingyue XiN Lynn HenryJames M RaeDaniel Louis HertzPublished in: Physiological genomics (2017)
Aromatase inhibitor (AI) therapy is highly efficacious in the treatment of estrogen receptor-positive breast cancer; however, in a subset of patients AI use is discontinued due to drug-induced musculoskeletal adverse events (MS-AE). Several studies have investigated the role of germline single nucleotide polymorphisms (SNPs) on patients' risk of MS-AEs; however, no associations have yet to be validated for translation into clinical practice. This study attempted to replicate SNPs in RANKL ( rs7984870 ) and OPG ( rs2073618 ) on the risk of AI-induced MS-AEs and screen for secondary associations with MS-AE-related treatment discontinuation and serum and urine markers of bone health. Previously reported associations were not replicated with our primary hypothesis, change in MS-AE from baseline to 3 mo; however, patients homozygous for the G allele of rs7984870 in RANKL had lower risk of MS-AE-associated treatment discontinuation in analyses of secondary phenotypes without statistical correction.
Keyphrases
- mass spectrometry
- end stage renal disease
- multiple sclerosis
- drug induced
- ms ms
- ejection fraction
- newly diagnosed
- chronic kidney disease
- artificial intelligence
- liver injury
- prognostic factors
- positive breast cancer
- clinical practice
- peritoneal dialysis
- body composition
- genome wide
- immune response
- combination therapy
- postmenopausal women
- replacement therapy
- bone marrow
- dna damage
- high resolution
- diabetic rats
- stress induced
- bone regeneration