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. 2013 Jun;24(6):1099-109.
doi: 10.1007/s10552-013-0187-z. Epub 2013 Mar 23.

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

Jeannette T Bensen  1 , Chiu Kit Tse, Sarah J Nyante, Jill S Barnholtz-Sloan, Stephen R Cole, Robert C Millikan
Affiliations

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

Jeannette T Bensen et al. Cancer Causes Control. 2013 Jun.

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.

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