Tumor Biology

, Volume 37, Issue 6, pp 8057–8066 | Cite as

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

  • Hongliang Liu
  • Fengqin Gao
  • Kristina R. Dahlstrom
  • Guojun Li
  • Erich M. Sturgis
  • Jose P. Zevallos
  • Qingyi Wei
  • Zhensheng Liu
Original Article

Abstract

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 (Ptrend = 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.

Keywords

DNA double strands break MicroRNA Genetic susceptibility Head and neck cancer Polymorphism 

Abbreviations

DSB

DNA double-strand break

SNP

Single nucleotide polymorphism

SCCHN

Squamous cell carcinoma of the head and neck

PBMCs

Peripheral blood mononuclear cells

OR

Odds ratio

CI

Confidence interval

Supplementary material

13277_2015_4682_MOESM1_ESM.docx (18 kb)
Supplementary Table 1(DOCX 17 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hongliang Liu
    • 1
    • 2
  • Fengqin Gao
    • 1
    • 2
  • Kristina R. Dahlstrom
    • 3
  • Guojun Li
    • 3
    • 4
  • Erich M. Sturgis
    • 3
    • 4
  • Jose P. Zevallos
    • 5
    • 6
  • Qingyi Wei
    • 1
    • 2
  • Zhensheng Liu
    • 1
    • 2
  1. 1.Duke Cancer InstituteDuke University Medical CenterDurhamUSA
  2. 2.Department of MedicineDuke University School of MedicineDurhamUSA
  3. 3.Departments of Head and Neck SurgeryThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Department of EpidemiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of Otolaryngology/Head and Neck SurgeryUniversity of North Carolina at Chapel HillChapel HillUSA
  6. 6.Department of Epidemiology, Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA

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