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

  • K.M. Taufiqul Arif
    Affiliations
    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
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  • Gabrielle Bradshaw
    Affiliations
    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
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  • Thanh T.N. Nguyen
    Affiliations
    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
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  • Robert A. Smith
    Affiliations
    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
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  • Rachel K. Okolicsanyi
    Affiliations
    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
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  • Philippa H. Youl
    Affiliations
    Cancer Council, Brisbane, Australia
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  • Larisa M. Haupt
    Affiliations
    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
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  • Lyn R. Griffiths
    Correspondence
    Address for correspondence: Lyn R Griffiths, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia
    Affiliations
    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
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Published:April 04, 2021DOI:https://doi.org/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

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      References

        • Rakha EA
        • Ellis IO.
        Modern classification of breast cancer: should we stick with morphology or convert to molecular profile characteristics.
        Adv Anat Pathol. 2011; 18: 255-267
        • Sarkar S
        • Mandal M.
        Breast cancer: classification based on molecular etiology influencing prognosis and prediction.
        in: Pesek K Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis. InTech, London2011: 69-84
        • van Schooneveld E
        • Wildiers H
        • Vergote I
        • Vermeulen PB
        • Dirix LY
        • Van Laere SJ.
        Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management.
        Breast Cancer Res. 2015; 17: 1-15
        • Turnbull C
        • Rahman N.
        Genetic predisposition to breast cancer: past, present, and future.
        Annu Rev Genomics Hum Genet. 2008; 9: 321-345
        • Davies EL.
        Breast cancer.
        Medicine (Baltimore). 2012; 40: 5-9
        • Eroles P
        • Bosch A
        • Alejandro Pérez-Fidalgo J
        • Lluch A
        Molecular biology in breast cancer: intrinsic subtypes and signaling pathways.
        Cancer Treat Rev. 2012; 38: 698-707
        • Véron A
        • Blein S
        • Cox DG.
        Genome-wide association studies and the clinic: a focus on breast cancer.
        Biomark Med. 2014; 8: 287-296
        • Kwong A
        • Ng EKO
        • Wong CLP
        • Ma ESK.
        MicroRNAs as new players for diagnosis, prognosis, and therapeutic targets in breast cancer.
        J Oncol. 2009; 2009305420
        • Andorfer CA
        • Necela BM
        • Thompson EA
        • Perez EA.
        MicroRNA signatures: clinical biomarkers for the diagnosis and treatment of breast cancer.
        Trends Mol Med. 2011; 17: 313-319
        • Dai X
        • Chen A
        • Bai Z.
        Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling.
        Sci Rep. 2014; 3: 1-10
        • Mishra PJ.
        MicroRNAs as promising biomarkers in cancer diagnostics.
        Biomark Res. 2014; 2: 19
        • Shafi G
        • Hasan TN
        • Syed NA
        • Paine A
        • Tegner J
        • Munshi A.
        Breast cancer MicroRNAs: clinical biomarkers for the diagnosis and treatment strategies.
        in: Barh D Omics Approaches in Breast Cancer: Towards Next-Generation Diagnosis, Prognosis and Therapy. Springer, New Delhi2014: 171-182
        • Kurozumi S
        • Yamaguchi Y
        • Kurosumi M
        • Ohira M
        • Matsumoto H
        • Horiguchi J.
        Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes.
        J Hum Genet. 2017; 62: 15-24
        • Nassar FJ
        • Nasr R
        • Talhouk R.
        MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.
        Pharmacol Ther. 2017; 172: 34-49
        • Cho WCS.
        MicroRNAs in cancer - from research to therapy.
        Biochim Biophys Acta. 2010; 1805: 209-217
        • Bertoli G
        • Cava C
        • Castiglioni I.
        MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer.
        Theranostics. 2015; 5: 1122-1143
        • Croce CM.
        Causes and consequences of microRNA dysregulation in cancer.
        Nat Rev Genet. 2009; 10: 704-714
        • Ferracin M
        • Veronese A
        • Negrini M.
        Micromarkers: miRNAs in cancer diagnosis and prognosis.
        Expert Rev Mol Diagn. 2010; 10: 297-308
        • Hashemi M.
        MicroRNAs: promising potential targets for cancer treatment.
        Gene Cell Tissue. 2016; 3: 1-7
        • Khan S
        • Greco D
        • Michailidou K
        • et al.
        MicroRNA related polymorphisms and breast cancer risk.
        PLoS One. 2014; 9: 1-12
        • Kolesnikov NN
        • Veryaskina YA
        • Titov SE
        • et al.
        Expression of micrornas in molecular genetic breast cancer subtypes.
        Cancer Treat Res Commun. 2016; 9: 6-11
        • Iorio MV
        • Casalini P
        • Piovan C
        • Braccioli L
        • Tagliabue E.
        Breast cancer and microRNAs: therapeutic impact.
        Breast. 2011; 20: S63-S70
        • Deng N
        • Zhou H
        • Fan H
        • Yuan Y.
        Single nucleotide polymorphisms and cancer susceptibility.
        Oncotarget. 2017; 8: 231-239
        • Dzikiewicz-Krawczyk A.
        MicroRNA polymorphisms as markers of risk, prognosis and treatment response in hematological malignancies.
        Crit Rev Oncol Hematol. 2015; 93: 1-17
        • Salzman DW
        • Weidhaas JB.
        SNPing cancer in the bud: microRNA and microRNA-target site polymorphisms as diagnostic and prognostic biomarkers in cancer.
        Pharmacol Ther. 2013; 137: 55-63
        • Mishra PJ
        • Mishra PJ
        • Banerjee D
        • Bertino JR.
        MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: introducing microRNA pharmacogenomics.
        Cell Cycle. 2008; 7: 853-858
        • Smith RA
        • Jedlinski DJ
        • Gabrovska PN
        • Weinstein SR
        • Haupt L
        • Griffiths LR.
        A genetic variant located in miR-423 is associated with reduced breast cancer risk.
        Cancer Genomics Proteomics. 2012; 9: 115-118
        • Lian H
        • Wang L
        • Zhang J.
        Increased risk of breast cancer associated with CC genotype of has-miR-146a Rs2910164 polymorphism in Europeans.
        PLoS One. 2012; 7: 1-7
        • Chacon-Cortes D
        • Smith RA
        • Haupt LM
        • Lea RA
        • Youl PH
        • Griffiths LR.
        Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility.
        BMC Med Genet. 2015; 16: 107
        • Chacon-Cortes D
        • Haupt LM
        • Lea RA
        • Griffiths LR.
        Comparison of genomic DNA extraction techniques from whole blood samples: a time, cost and quality evaluation study.
        Mol Biol Rep. 2012; 39: 5961-5966
        • Chacon-Cortes D
        • Smith RA
        • Haupt LM
        • Lea RA
        • Youl PH
        • Griffiths LR.
        Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility.
        BMC Med Genet. 2015; 16: 1-11
        • Bradshaw G
        • Haupt LM
        • Aquino EM
        • Lea RA
        • Sutherland HG
        • Griffiths LR.
        Single nucleotide polymorphisms in MIR143 contribute to protection against non-Hodgkin lymphoma (NHL) in Caucasian populations.
        Genes (Basel). 2019; 10: 185
        • Solé X
        • Guinó E
        • Valls J
        • Iniesta R
        • Moreno V.
        SNPStats: a web tool for the analysis of association studies.
        Bioinformatics. 2006; 22: 1928-1929
        • Purcell S
        • Neale B
        • Todd-Brown K
        • et al.
        PLINK: a tool set for whole-genome association and population-based linkage analyses.
        Am J Hum Genet. 2007; 81: 559-575
        • Cummings MC
        • Chambers R
        • Simpson PT
        • Lakhani SR.
        Molecular classification of breast cancer: is it time to pack up our microscopes?.
        Pathology. 2011; 43: 1-8
        • Kontorovich T
        • Levy A
        • Korostishevsky M
        • Nir U
        • Friedman E.
        Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women.
        Int J Cancer. 2010; 127: 589-597
        • Pelletier C
        • Weidhaas JB.
        MicroRNA binding site polymorphisms as biomarkers of cancer risk.
        Expert Rev Mol Diagn. 2010; 10: 817-829
        • Pipan V
        • Zorc M
        • Kunej T.
        MicroRNA polymorphisms in cancer: a literature analysis.
        Cancers (Basel). 2015; 7: 1806-1814
        • Preskill C
        • Weidhaas JB.
        SNPs in microRNA binding sites as prognostic and predictive cancer biomarkers.
        Crit Rev Oncog. 2013; 18: 327-340
        • Ramírez-Bello J
        • Jiménez-Morales M.
        [Functional implications of single nucleotide polymorphisms (SNPs) in protein-coding and non-coding RNA genes in multifactorial diseases].
        Gac Med Mex. 2017; 153: 238-250
        • Ryan BM
        • Robles AI
        • Harris CC.
        Genetic variation in microRNA networks: the implications for cancer research.
        Nat Rev Cancer. 2011; 10: 389-402
        • Wu D
        • Yang G
        • Zhang L
        • Xue J
        • Wen Z
        • Li M.
        Genome-wide association study combined with biological context can reveal more disease-related SNPs altering microRNA target seed sites.
        BMC Genomics. 2014; 15: 1-13
        • Lindström S
        • Ablorh A
        • Chapman B
        • et al.
        Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities.
        Breast Cancer Res. 2016; 18: 1-13
        • Thanh NTN
        • Lan NTT
        • Phat PT
        • Giang NDT
        • Hue NT.
        Two polymorphisms, rs2046210 and rs3803662, are associated with breast cancer risk in a Vietnamese case-control cohort.
        Genes Genet Syst. 2018; 93: 101-109
        • Mavaddat N
        • Pharoah PDP
        • Michailidou K
        • et al.
        Prediction of breast cancer risk based on profiling with common genetic variants.
        J Natl Cancer Inst. 2015; 107: djv036
        • Chan M
        • Ji SM
        • Liaw CS
        • et al.
        Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.
        Breast Cancer Res Treat. 2012; 136: 209-220
        • Liang H
        • Yang X
        • Chen L
        • et al.
        Heterogeneity of breast cancer associations with common genetic variants in FGFR2 according to the intrinsic subtypes in southern Han Chinese women.
        Biomed Res Int. 2015; 2015626948
        • Cui F
        • Wu D
        • Wang W
        • He X
        • Wang M.
        Variants of FGFR2 and their associations with breast cancer risk: a HUGE systematic review and meta-analysis.
        Breast Cancer Res Treat. 2016; 155: 1-23
        • Fletcher MNC
        • Castro MAA
        • Wang X
        • et al.
        Master regulators of FGFR2 signalling and breast cancer risk.
        Nat Commun. 2013; 4: 1-12
        • Camps C
        • Buffa FM
        • Colella S
        • et al.
        Hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer.
        Clin Cancer Res. 2008; 14: 1340-1348
        • Chan YC
        • Banerjee J
        • Choi SY
        • Sen CK.
        miR-210: the master hypoxamir.
        Microcirculation. 2012; 19: 215-223
        • Rothé F
        • Ignatiadis M
        • Chaboteaux C
        • et al.
        Global microRNA expression profiling identifies MiR-210 associated with tumor proliferation, invasion and poor clinical outcome in breast cancer.
        PLoS One. 2011; 6: e20980
        • Volinia S
        • Galasso M
        • Sana ME
        • et al.
        Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA.
        Proc Natl Acad Sci U S A. 2012; 109: 3024-3029
        • Shidfar A
        • Costa FF
        • Scholtens D
        • et al.
        Expression of miR-18a and miR-210 in normal breast tissue as candidate biomarkers of breast cancer risk.
        Cancer Prev Res. 2017; 10: 89-97
        • Li P
        • Cao Q
        • Shao P-F
        • et al.
        Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population.
        Asian J Androl. 2012; 14: 864-869
        • Liu B
        • Liu Q
        • Song Y
        • et al.
        Polymorphisms of HIF1A gene are associated with prognosis of early stage non-small-cell lung cancer patients after surgery.
        Med Oncol. 2014; 31: 1-9
        • Yamamoto Y
        • Kiyohara C
        • Ogata-Suetsugu S
        • Hamada N
        • Nakanishi Y.
        Association between genetic polymorphisms involved in the hypoxia-inducible factor pathway and lung cancer risk: a case-control study in Japan.
        Asia Pac J Clin Oncol. 2017; 13: 234-242
        • Qin C
        • Cao Q
        • Ju X
        • et al.
        The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma.
        Ann Oncol. 2012; 23: 981-989
        • Guo X
        • Li D
        • Chen Y
        • et al.
        SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.
        Sci Rep. 2015; 5: 1-9
        • Wang X
        • Ren H
        • Zhao T
        • et al.
        Single nucleotide polymorphism in the microRNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes.
        Oncotarget. 2016; 7: 13717-13729
        • Liu D-F
        • Wu J-T
        • Wang J-M
        • Liu Q-Z
        • Gao Z-L
        • Liu Y-X.
        MicroRNA expression profile analysis reveals diagnostic biomarker for human prostate cancer.
        Asian Pac J Cancer Prev. 2012; 13: 3313-3317
        • Han Y-J
        • Zhang J
        • Zheng Y
        • Huo D
        • Olopade OI.
        Genetic and epigenetic regulation of TOX3 expression in breast cancer.
        PLoS One. 2016; 11e0165559
        • Cowper-Sallari R
        • Zhang X
        • Wright JB
        • et al.
        Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression.
        Nat Genet. 2012; 44: 1191-1198
        • Han M-R
        • Deming-Halverson S
        • Cai Q
        • et al.
        Evaluating 17 breast cancer susceptibility loci in the Nashville breast health study.
        Breast Cancer. 2015; 22: 544-551
        • Couch FJ
        • Kuchenbaecker KB
        • Michailidou K
        • et al.
        Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.
        Nat Commun. 2016; 7: 11375
        • Lee CPL
        • Irwanto A
        • Salim A
        • et al.
        Breast cancer risk assessment using genetic variants and risk factors in a Singapore Chinese population.
        Breast Cancer Res. 2014; 16: R64
        • Qin Q
        • Wei F
        • Li B.
        Multiple functions of hypoxia-regulated miR-210 in cancer.
        J Exp Clin Cancer Res. 2014; 33: 1-10
        • Nalwoga H
        • Ahmed L
        • Arnes JB
        • Wabinga H
        • Akslen LA.
        Strong expression of hypoxia-inducible factor-1α (HIF-1α) is associated with Axl expression and features of aggressive tumors in African breast cancer.
        PLoS One. 2016; 11: 1-17