| Summary: | Breast cancer is a complex disease with heterogeneity in tumour characteristics and treatment response. Recently, Asian breast cancer patients were reported to have elevated immune scores in comparison to Caucasian breast cancer patients, however, germline genetic determinants associated with immune scores in Asian breast cancer patients remain undercharacterised. This study aims to identify the germline genetic variants associated with heritable immune scores in Asian breast tumours and determine the cellular pathways that drive immune scores within this population.
By evaluating 112 immune scores that have previously been described in literature, we observed significantly higher heritability in Asian breast tumours compared to Caucasians. The major histocompatibility complex class-I (MHC-I) immune score had high heritability in both cohorts. By conducting a genome-wide association study (GWAS), the findings revealed, as predicted, the HLA locus on chromosome (chr) 6 in both Asian and Caucasian cohorts.
Regulatory T (Treg) cells, Immune non-small cell lung cancer (NSCLC) score, Triggering receptor expressed on myeloid cells 1 (TREM1) score and T follicular helper (Tfh) cells were the most heritable immune scores in Asian breast tumours. A total of 37 candidate SNPs were identified through GWAS. Expression quantitative trait loci (eQTL) analysis and a review of current literature revealed variants in TNFRSF13B, PRKCQ, IL2RA, and MIR149 as candidate cis-eQTL loci with potential roles in immune function and immune scores. Taken together, these findings suggest that there may be a population-specific genetic influence on heritable immune traits. This study identifies candidate variants that may underlie these observed differences.
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