학술논문
Genetic Association Analysis Implicates Six MicroRNA-Related SNPs With Increased Risk of Breast Cancer in Australian Caucasian Women.
Document Type
Academic Journal
Author
Arif KMT; 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.; Bradshaw G; 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.; Nguyen TTN; 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.; Smith RA; 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.; Okolicsanyi RK; 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.; Youl PH; Cancer Council, Brisbane, Australia.; Haupt LM; 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.; Griffiths LR; 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.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 100898731 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-0666 (Electronic) Linking ISSN: 15268209 NLM ISO Abbreviation: Clin Breast Cancer Subsets: MEDLINE
Subject
Language
English
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.
(Copyright © 2021. Published by Elsevier Inc.)
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.
(Copyright © 2021. Published by Elsevier Inc.)