ArticlePloS one2015
RANKL and OPG Polymorphisms Are Associated with Aromatase Inhibitor-Related Musculoskeletal Adverse Events in Chinese Han Breast Cancer Patients.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- Genome-wide association study of aromatase inhibitor discontinuation due to musculoskeletal symptoms.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Trial
- A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Trial
- ESR1 polymorphisms were associated with aromatase inhibitors induced musculoskeletal symptoms in breast cancer patients.Breast cancer research and treatment · 2026Article
- No evidence for genotype-treatment interactions with breast cancer endocrine therapy adverse effects in UK Biobank.NPJ breast cancer · 2026Article
- Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients.Metabolites · 2025Article
- Musculoskeletal symptoms associated with aromatase inhibitors in the treatment of early breast cancer: A scoping review of risk factors and outcomes.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential.Cancers · 2025Review
- Incorporation of emergent symptoms and genetic covariates improves prediction of aromatase inhibitor therapy discontinuation.JAMIA open · 2024Article
- Article
- Article
- Further Evidence That OPG rs2073618 Is Associated With Increased Risk of Musculoskeletal Symptoms in Patients Receiving Aromatase Inhibitors for Early Breast Cancer.Frontiers in genetics · 2021Article
- Aromatase Inhibitors-Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects.International journal of molecular sciences · 2020Review
- Genetic Underpinnings of Musculoskeletal Pain During Treatment With Aromatase Inhibitors for Breast Cancer: A Biological Pathway Analysis.Biological research for nursing · 2020Article
- Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors.Breast (Edinburgh, Scotland) · 2020Article
- The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics.Oncology and therapy · 2019Review
- Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse events during aromatase inhibitor treatment for breast cancer.Physiological genomics · 2018Article
- Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm.Cancer medicine · 2018Article
- Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.Breast cancer research and treatment · 2017Article
- Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.Pharmacogenomics · 2017Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer patients treated with aromatase inhibitors (AIs) may experience musculoskeletal adverse events (MS-AEs). Several studies have confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone health. Therefore, this study aimed to analyze the relationship between the serum levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI-related MS-AEs. METHODOLOGY AND PRINCIPAL
findingsPatients with early stage, hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We included 208 cases with AI-related MS-AEs and 212 without (controls). The levels of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG and lumbar spine BMD were measured, and questionnaires were completed. We analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR-based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS-AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870 CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05). CONCLUSIONS AND SIGNIFICANCE: In conclusion, the RANKL and OPG risk genotypes synergize to negatively impact bone health and predispose breast cancer patients to AI-related MS-AEs.
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