title: Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jbensen@med.unc.edu
authors.forename: Jeannette T
authors.initials: JT
authors.lastname: Bensen
authors.forename: Chiu Kit
authors.initials: CK
authors.lastname: Tse
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nyante
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Cole
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D035683:MicroRNAs