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A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck.

Publication ,  Journal Article
Liu, H; Gao, F; Dahlstrom, KR; Li, G; Sturgis, EM; Zevallos, JP; Wei, Q; Liu, Z
Published in: Tumour Biol
June 2016

DNA double-strand breaks (DSBs) are one of the most serious forms of DNA damage to the cell, causing genomic instability and ultimately carcinogenesis. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) at the micro RNA (miRNA)-binding sites of DSB repair genes may influence cancer risk by dysregulating target gene expression. To test our hypothesis, we firstly performed functional prediction for common SNPs in DSB genes and found 12 potentially functional SNPs located at the miRNA-binding sites. We then investigated their associations with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1087 patients and 1090 cancer-free controls in a non-Hispanic white population. As a result, SNP rs7213430 in BRIP1 was found to be significantly associated with cancer risk (P trend = 0.021). Compared with the AA homozygotes, the G allele carriers had an increased risk of SCCHN (adjusted OR 1.16, 95 % CI 1.02-1.31). Marginal significance was found for another SNP rs15869 in BRCA2 (P = 0.053). Further, functional analyses showed that SNP rs7213430 is within the miR-101 seed-binding region, and the variant G allele could lead to significantly lower luciferase activity and BRIP1 mRNA expression, compared to the A allele with the presence of miR-101. Our results suggested that SNP rs7213430 in the 3'-UTR of BRIP1 might contribute to SCCHN susceptibility by affecting the binding activity of miR-101 and resulting in a decreased BRIP1 expression. Additional larger population and functional studies are warranted to confirm our findings.

Duke Scholars

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Published In

Tumour Biol

DOI

EISSN

1423-0380

Publication Date

June 2016

Volume

37

Issue

6

Start / End Page

8057 / 8066

Location

Netherlands

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • ROC Curve
  • RNA, Messenger
  • RNA Helicases
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging
 

Citation

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Liu, H., Gao, F., Dahlstrom, K. R., Li, G., Sturgis, E. M., Zevallos, J. P., … Liu, Z. (2016). A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck. Tumour Biol, 37(6), 8057–8066. https://doi.org/10.1007/s13277-015-4682-6
Liu, Hongliang, Fengqin Gao, Kristina R. Dahlstrom, Guojun Li, Erich M. Sturgis, Jose P. Zevallos, Qingyi Wei, and Zhensheng Liu. “A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck.Tumour Biol 37, no. 6 (June 2016): 8057–66. https://doi.org/10.1007/s13277-015-4682-6.
Liu H, Gao F, Dahlstrom KR, Li G, Sturgis EM, Zevallos JP, et al. A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck. Tumour Biol. 2016 Jun;37(6):8057–66.
Liu, Hongliang, et al. “A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck.Tumour Biol, vol. 37, no. 6, June 2016, pp. 8057–66. Pubmed, doi:10.1007/s13277-015-4682-6.
Liu H, Gao F, Dahlstrom KR, Li G, Sturgis EM, Zevallos JP, Wei Q, Liu Z. A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck. Tumour Biol. 2016 Jun;37(6):8057–8066.
Journal cover image

Published In

Tumour Biol

DOI

EISSN

1423-0380

Publication Date

June 2016

Volume

37

Issue

6

Start / End Page

8057 / 8066

Location

Netherlands

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • ROC Curve
  • RNA, Messenger
  • RNA Helicases
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging