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

被引:64
作者
Bensen, Jeannette T. [1 ,2 ]
Tse, Chiu Kit [1 ]
Nyante, Sarah J. [3 ]
Barnholtz-Sloan, Jill S. [4 ]
Cole, Stephen R. [1 ]
Millikan, Robert C. [1 ,2 ]
机构
[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[3] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[4] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA
关键词
MicroRNA; Breast cancer; Germline; Single nucleotide polymorphism; Risk; Survival; SINGLE-NUCLEOTIDE POLYMORPHISMS; BINDING-SITES; CELL-LINES; ENVIRONMENT INTERACTIONS; AFRICAN-AMERICAN; GENETIC-VARIANTS; MESSENGER-RNA; EXPRESSION; POPULATION; APOPTOSIS;
D O I
10.1007/s10552-013-0187-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1099 / 1109
页数:11
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