A functional polymorphism in microRNA-196a2 is associated with increased susceptibility to non-Hodgkin lymphoma

Aberrant expression and structural alterations of microRNAs (miRNAs) play important roles in tumorigenesis. The miRNA-196a2 polymorphism is associated with tumorigenesis, but its association with non-Hodgkin lymphoma (NHL) remains unexplored. We evaluated the association between the miRNA-196a2 T>C polymorphism (rs11614913) and NHL risk in a case-control study of 318 NHL cases and 320 healthy controls. We also examined miRNA-196a expression in tissue samples from NHL patients (n = 59). The TC and CC genotypes were associated with cancer risk in NHL [odds ratio (OR) = 1.384, confidence interval (CI) = 1.010-1.898 for TC vs. TT, and OR = 1.822, 95 % CI = 1.163-2.853 for CC vs. TT]. Analysis of the association between this polymorphism and the clinicopathology of NHL showed that the combined TC/CC genotypes were associated with Ann Arbor stage (OR = 1.852, 95 % CI = 1.139-3.010), bone marrow invasion (OR = 1.850, 95 % CI = 1.062-3.223), and B symptoms (OR = 1.852, 95 % CI =  .154-2.972), but not with immunohistological subtype, lymph node size, age, or gender. In addition, the CC or CC/TC genotypes were associated with significantly higher levels of mature miR-196a (p = 0.002 or 0.008) in a genotype-phenotype correlation analysis. Our findings suggest that the miR-196a2 polymorphism may increase the risk of NHL by altering the expression of mature miR-196a.