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miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

BACKGROUND: Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China. METHO...

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Autores principales: He, Na, Zheng, Hong, Li, Pei, Zhao, Yanrui, Zhang, Wei, Song, Fengju, Chen, Kexin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087002/
https://www.ncbi.nlm.nih.gov/pubmed/25003827
http://dx.doi.org/10.1371/journal.pone.0102093
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author He, Na
Zheng, Hong
Li, Pei
Zhao, Yanrui
Zhang, Wei
Song, Fengju
Chen, Kexin
author_facet He, Na
Zheng, Hong
Li, Pei
Zhao, Yanrui
Zhang, Wei
Song, Fengju
Chen, Kexin
author_sort He, Na
collection PubMed
description BACKGROUND: Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China. METHODS: We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set. RESULTS: In stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant. CONCLUSION: Through a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.
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spelling pubmed-40870022014-07-14 miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk He, Na Zheng, Hong Li, Pei Zhao, Yanrui Zhang, Wei Song, Fengju Chen, Kexin PLoS One Research Article BACKGROUND: Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China. METHODS: We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set. RESULTS: In stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant. CONCLUSION: Through a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association. Public Library of Science 2014-07-08 /pmc/articles/PMC4087002/ /pubmed/25003827 http://dx.doi.org/10.1371/journal.pone.0102093 Text en © 2014 He et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
He, Na
Zheng, Hong
Li, Pei
Zhao, Yanrui
Zhang, Wei
Song, Fengju
Chen, Kexin
miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title_full miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title_fullStr miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title_full_unstemmed miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title_short miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
title_sort mir-485-5p binding site snp rs8752 in hpgd gene is associated with breast cancer risk
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087002/
https://www.ncbi.nlm.nih.gov/pubmed/25003827
http://dx.doi.org/10.1371/journal.pone.0102093
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