Abstract
Introduction
Breast cancer (BC), a heterogeneous disease, features microRNA-related single nucleotide
polymorphisms (miRSNPs) as underlying factors of BC development, thus providing targets
for novel diagnostic and therapeutic strategies. This study investigated miRSNPs in
BC susceptibility in Australian Caucasian women.
Patients and Methods
The study population included patients 33 to 80 years of age stratified by molecular
subtypes of breast tumors (luminal A, 47.59%), stage (stage I, 36.96%), tumor-type
(ductal, 44.95%), grading (intermediate, 35.52%), size (10.1-25 mm, 31.14%), and lymph
node (sentinel negative, 38.93%). Sixty-five miRSNPs underwent allelic analysis in
two independent case–control cohorts (GU-CCQ-BB, 377 cases and 521 controls; GRC-BC,
267 cases and 201 controls) using a MassARRAY platform. GU-CCQ-BB, GRC-BC, and the
combined populations (BC-CA) (644 cases and 722 controls) underwent independent statistical
analysis.
Results
In the GU-CCQ-BB population, miRSNPs TET2-rs7670522, ESR1-rs2046210, FGFR2-rs1219648, MIR210-rs1062099, HIF1A-rs2057482, and CASC16-rs4784227 were found to be associated with increased BC risk (P ≤ .05). Only ESR1-rs2046210 was also significantly associated (P ≤ .05) when replicated in the GRC-BC and BC-CA populations. No significant association
was correlated with BC-clinical features (pathological types and ER/PR/HER2 status); however, MIR210-rs1062099 was found to be significantly associated (P ≤ .05) with age (>50 years) in the GU-CCQ-BB cohort.
Conclusion
This is the first study to demonstrate the association of MIR210-rs1062099 and TET2-rs7670522 with increased BC risk. Additionally, four previously reported SNPs (ESR1-rs2046210, FGFR2-rs1219648, HIF1A-rs2057482, and CASC16-rs4784227) were confirmed as BC risk variants. Replication and functional studies
in larger Caucasian cohorts are necessary to elucidate the role of these miRSNPS in
the development of BC.
Keywords
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Article Info
Publication History
Published online: April 04, 2021
Accepted:
March 26,
2021
Received in revised form:
February 24,
2021
Received:
September 10,
2020
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
