A genome-wide association study (GWAS) meta-analysis of chemotherapy-associated cognitive impairment (CACI) in Asian early-stage breast cancer patients (ESBC).

Authors

null

Terence NG

Department of Pharmacy, National University of Singapore, Singapore, Singapore

Terence NG , Hui Ling Angie Yeo , Maung Shwe , Yan Xiang Gan , Koon Mian Foo , Wei-Jen Kiley Loh , Si-Lin Koo , Wen Yee Chay , Tira Jing Ying Tan , Sok Yuen Beh , Hsuen Elaine Lim , Guek Eng Lee , Rebecca Alexandra Dent , Yoon Sim Yap , Raymond C.H. Ng , Pak Yan Pat Chu , Chiea Chuen Khor , Han Kiat Ho , Alexandre Chan

Organizations

Department of Pharmacy, National University of Singapore, Singapore, Singapore, Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore, Department of Pharmacy, K.K. Women’s and Children’s Hospital, Singapore, Singapore, National Cancer Centre Singapore, Singapore, Singapore, Division of Medical Oncology, National Cancer Centre, Singapore, Singapore, Singapore Cord Blood Bank, Singapore, Singapore, Genome Institute of Singapore, Singapore, Singapore

Research Funding

Other

Background: Genetic variations among genes regulating neuronal function, neurotransmission and plasticity may contribute to varying risk of CACI. In order to fully elucidate the complex genetic structure underlying CACI, a GWAS meta-analysis was performed to identify genetic variants associated with CACI among ESBC patients. Methods: A GWAS meta-analysis of two independent cohorts totaling 266 chemotherapy-receiving ESBC patients (mean age: 51.0 ± 9.2 years; 80.8% Chinese) was performed. Patients’ self-perceived cognitive function was assessed using the validated FACT-Cog (v.3). Genome-wide genotyping was performed using the Illumina HumanOmniExpress-24 version 1.1 BeadChips kits. Each beadchip contains over 700,000 genetic markers. Covariates included in the meta-analysis were the first two dimensions of the multi-dimensional scaling. Results: After applying stringent quality control measures and removing four population outliers, data from 546,399 SNPs were available for 84 cases and 170 controls. In the meta-analysis, two SNPs (rs6443264 and rs4686371) exceeded the suggestive threshold of P< 1×10-5 (Table). Following adjustment for the first two MDS dimensions in the meta-analysis, both SNPs remained as top two SNPs with P< 1×10-4. Both rs6443264 and rs4686371 are located in chromosome 3p25 and lie in the intronic regions encoding OGG1 and ARPC4 genes, respectively. Alteration of the OGG1 gene could compromise the functions of downstream neuronal genes, and modification of the ARPC4 gene could affect the formation of the actin-related protein 2/3 complex and impair memory formation. Conclusions: To the best of our knowledge, this is the first GWAS meta-analysis to identify two loci, namely rs6443264 and rs4686371 that are suggestive of genome-wide association with CACI among Asian ESBC patients.

SNPCohortMAF
cases
MAF
controls
PPer allele OR95% CI
rs6443264A0.570.291.70 × 10-53.261.89 to 5.64
B0.510.373.19 × 10-21.791.05 to 3.08
Meta-analysis7.21 × 10-62.411.64 to 3.53
rs4686371A0.590.311.18 × 10-53.321.93 to 5.74
B0.530.394.18 × 10-21.741.02 to 2.98
Meta-analysis7.99 × 10-62.391.63 to 3.50

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Patient and Survivor Care

Track

Patient and Survivor Care

Sub Track

Palliative Care and Symptom Management

Citation

J Clin Oncol 35, 2017 (suppl; abstr 10096)

DOI

10.1200/JCO.2017.35.15_suppl.10096

Abstract #

10096

Poster Bd #

85

Abstract Disclosures

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