Title:Five Common Functional Polymorphisms in microRNAs (rs2910164, rs2292832, rs11614913, rs3746444, rs895819) and the Susceptibility to Breast Cancer: Evidence from 8361 Cancer Cases and 8504 Controls
Volume: 21
Issue: 11
Author(s): Zhi-Jun Dai, Yong-Ping Shao, Xi-Jing Wang, Dan Xu, Hua-Feng Kang, Hong-Tao Ren, Wei-Li Min, Shuai Lin, Meng Wang and Zhang-Jun Song
Affiliation:
Keywords:
Breast cancer, miRNAs, single nucleotide polymorphism, cancer susceptibility, meta-analysis.
Abstract: Objectives: To evaluate the relationship between the five common polymorphisms in miRNAs (miR-146a
rs2910164 G>C, miR-149 rs2292832 C>T, miR-196a2 rs11614913 C>T, miR-499 rs3746444 A>G and miR-27a rs895819
A>G), and breast cancer (BC) risk.
Methods: Meta-analyses were performed on 15 published studies involving 8, 361 BC patients and 8, 504 cancer-free controls.
There were 8 studies with 4, 314 cases and 4, 485 controls for rs2910164, 3 studies with 1, 439 cases and 1, 508 controls
for rs2292832, 10 studies with 4, 618 cases and 5, 590 controls for rs11614913, 5 studies with 2, 924 cases and 3, 563 controls for
rs3746444, and 5 studies with 2, 912 cases and 3, 697 controls for rs895819. Summary odds ratios (ORs) and 95% confidence intervals
(CIs) were used to evaluate the BC risk.
Results: Meta-analyses showed that rs2910164 (miR-146a) was associated with BC risk in Caucasian population (homozygote comparison:
OR = 1.29, 95%CI = 1.02-1.63, P=0.03; dominant model: OR = 1.31, 95% CI = 1.05-1.65, P=0.02), whereas negative results were
obtained for Asians in all genetic models. rs11614913 (miR-196a2) was associated with BC risk in the overall population based on the
recessive model (OR = 0.89, 95% CI = 0.80-0.99, P=0.03). Association of rs3746444 (miR-499) with BC risk was detected under three
genetic models (allele contrast genetic model: OR = 1.13, 95%CI = 1.03-1.23, P=0.007; homozygote comparison: OR = 1.36, 95 %CI =
1.10-1.69, P=0.005 and recessive model: OR = 1.38, 95% CI = 1.12-1.70, P=0.003). When stratified by ethnicity, the effects remained in
Asians. rs895819 (miR-27a) was associated with BC risk in the overall population based on the allele contrast genetic model (OR = 0.91,
95%CI = 0.85-0.98, P=0.02); heterozygote comparison (OR = 0.89, 95 %CI = 0.80-0.99, P=0.03) and the dominant model (OR = 0.89,
95% CI = 0.80-0.98, P=0.02). However, there was no association between rs2292832 (miR-149) polymorphism and BC susceptibility.
Conclusion: Our meta-analysis results suggested that the rs2910164 and rs3746444 polymorphisms are associated with increased BC
risk, while the rs11614913 and rs895819 polymorphisms correlate with reduced BC risk.
