Cancer Causes & Control

, Volume 24, Issue 6, pp 1099–1109

Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study

  • Jeannette T. Bensen
  • Chiu Kit Tse
  • Sarah J. Nyante
  • Jill S. Barnholtz-Sloan
  • Stephen R. Cole
  • Robert C. Millikan
Original paper

Abstract

Purpose

Common germline variation in the 5′ region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians.

Methods

We genotyped nine single nucleotide polymorphisms (SNPs) within six miRNA gene regions previously associated with breast cancer, in 1,972 cases and 1,776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to evaluate SNP association with breast cancer risk. Additionally, hazard ratios (HRs) for breast cancer-specific mortality were estimated.

Results

Two miR-185 SNPs provided suggestive evidence of an inverse association with breast cancer risk (rs2008591, OR = 0.72 (95 % CI = 0.53–0.98, p value = 0.04) and rs887205, OR = 0.71 (95 % CI = 0.52–0.96, p value = 0.03), respectively) among African Americans. Two SNPs, miR-34b/34c (rs4938723, HR = 0.57 (95 % CI = 0.37–0.89, p value = 0.01)) and miR-206 (rs6920648, HR = 0.77 (95 % CI = 0.61–0.97, p value = 0.02)), provided evidence of association with breast cancer survival. Further adjustment for stage resulted in more modest associations with survival (HR = 0.65 [95 % CI = 0.42–1.02, p value = 0.06] and HR = 0.79 [95 % CI = 0.62–1.00, p value = 0.05, respectively]).

Conclusions

Our results suggest that germline variation in the 5′ region proximal to pre-miRNA gene sequences may be associated with breast cancer risk among African Americans and breast cancer-specific survival generally; however, further validation is needed to confirm these findings.

Keywords

MicroRNA Breast cancer Germline Single nucleotide polymorphism Risk Survival 

Abbreviations

3′-UTR

3′-Untranslated region

AIMs

Ancestry informative markers

CBCS

Carolina Breast Cancer Study

cDNA

Complementary DNA made from an mRNA template

CI

Confidence interval

CIS

Breast carcinoma in situ

HR

Hazard ratio

kb

Kilobase

LD

Linkage disequilibrium

MAF

Minor allele frequency

miRNA or miR

MicroRNA

mRNA

Messenger RNA

nt

Nucleotide

OR

Odds ratio

Pol II

Polymerase II

Pol III

Polymerase III

pre-miRNA

Precursor microRNA

pri-miRNA

Primary miRNA transcript

SNP

Single nucleotide polymorphism

Supplementary material

10552_2013_187_MOESM1_ESM.pdf (95 kb)
Supplementary material 1 (PDF 95 kb)
10552_2013_187_MOESM2_ESM.pdf (77 kb)
Supplementary material 2 (PDF 77 kb)
10552_2013_187_MOESM3_ESM.pdf (178 kb)
Supplementary material 3 (PDF 178 kb)
10552_2013_187_MOESM4_ESM.pdf (69 kb)
Supplementary material 4 (PDF 69 kb)
10552_2013_187_MOESM5_ESM.pdf (146 kb)
Supplementary material 5 (PDF 146 kb)
10552_2013_187_MOESM6_ESM.pdf (123 kb)
Supplementary material 6 (PDF 122 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Jeannette T. Bensen
    • 1
    • 2
  • Chiu Kit Tse
    • 1
  • Sarah J. Nyante
    • 3
  • Jill S. Barnholtz-Sloan
    • 4
  • Stephen R. Cole
    • 1
  • Robert C. Millikan
    • 1
    • 2
  1. 1.Department of EpidemiologyUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Lineberger Comprehensive Cancer Center of the University of North Carolina at Chapel HillChapel HillUSA
  3. 3.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of HealthDepartment of Health and Human ServicesBethesdaUSA
  4. 4.Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA

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