Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study
- First Online:
- 723 Downloads
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.
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.
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]).
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.
KeywordsMicroRNA Breast cancer Germline Single nucleotide polymorphism Risk Survival
Ancestry informative markers
Carolina Breast Cancer Study
Complementary DNA made from an mRNA template
Breast carcinoma in situ
Minor allele frequency
- miRNA or miR
- Pol II
- Pol III
Primary miRNA transcript
Single nucleotide polymorphism
- 12.Sethupathy P, Borel C, Gagnebin M et al (2007) Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 81:405–413. doi:10.1086/519979 PubMedCrossRefGoogle Scholar
- 51.Vogt M, Munding J, Gruner M et al (2011) Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch 458:313–322. doi:10.1007/s00428-010-1030-5 PubMedCrossRefGoogle Scholar
- 61.Adams BD, Furneaux H, White BA (2007) The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 21:1132–1147. doi:10.1210/me.2007-0022 PubMedCrossRefGoogle Scholar