A Promoter Polymorphism of Pri-miR-34b/c Is Associated With an Increased Risk of Breast Cancer
P53 can bind to the promoter of miR-34a/b/c, inducing their expression at the transcriptional level. Previous reports have shown that TP-53 and miR-34b/c may play crucial roles in carcinogenesis. We conducted a case-control study to investigate the association between miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms and the risk of breast cancer (BC) in Chinese women. We genotyped the two polymorphisms in 228 BC patients and 307 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the miR-34b/c rs4938723 CT genotype and C allele were associated with significantly increased risks of BC compared with the TT genotype and T allele (CT vs. TT: OR = 1.81, 95 % CI, 1.24 – 2.65, P = 0.002; C vs. T: OR = 1.36, 95 % CI, 1.06 – 1.74, P = 0.016, respectively). Moreover, a significant association between the cases and controls was also observed in a dominant model (OR = 1.75; 95 % CI, 1.22 – 2.51, P = 0.002). Stratified analysis showed that patients with the miR-34b/c rs4938723CT genotype were more likely to develop clinical stages III-IV (OR = 2.17; 95 % CI, 1.10 – 4.28, P = 0.02). Combined analysis showed that subjects carrying the rs4938723 CT/CC and TP-53 CG/CC genotypes were associated with an increased risk of BC compared with the rs4938723 TT and TP-53 CG/CC genotypes (OR = 1.78; 95 % CI, 1.12 – 2.83, P = 0.015). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the risk of BC.
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