Genetic Association Analysis Implicates Six MicroRNA-Related SNPs With Increased Risk of Breast Cancer in Australian Caucasian Women

K M Taufiqul Arif; Gabrielle Bradshaw; Thanh T N Nguyen; Robert A Smith; Rachel K Okolicsanyi; Philippa H Youl; Larisa M Haupt; Lyn R Griffiths

doi:10.1016/j.clbc.2021.03.012

Genetic Association Analysis Implicates Six MicroRNA-Related SNPs With Increased Risk of Breast Cancer in Australian Caucasian Women

Clin Breast Cancer. 2021 Dec;21(6):e694-e703. doi: 10.1016/j.clbc.2021.03.012. Epub 2021 Apr 5.

Authors

K M Taufiqul Arif¹, Gabrielle Bradshaw¹, Thanh T N Nguyen¹, Robert A Smith¹, Rachel K Okolicsanyi¹, Philippa H Youl², Larisa M Haupt¹, Lyn R Griffiths³

Affiliations

¹ Queensland University of Technology (QUT), Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia.
² Cancer Council, Brisbane, Australia.
³ Queensland University of Technology (QUT), Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. Electronic address: lyn.griffiths@qut.edu.au.

PMID: 33952417
DOI: 10.1016/j.clbc.2021.03.012

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: Breast Cancer; Genetic Association Study; Genotyping; Single Nucleotide Polymorphism (SNP); microRNA (miRNA).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Australia
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Case-Control Studies
Female
Genetic Predisposition to Disease
Humans
MicroRNAs / metabolism*
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
White People / statistics & numerical data*

Substances

MIRN17 microRNA, human
MicroRNAs