RUNX3 polymorphisms and the susceptibility to cervical cancer and cervical intraepithelial neoplasia in Western China

Runt-related transcription factor 3 (RUNX3) is recognized to play essential roles in various tumors. But the effect between genetic variations and the susceptibility to tumor remains unclear, so does it in cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). Three single nucleotide polymorphisms (SNP) of the RUNX3 gene were selected to evaluate whether they were associated with CC and CIN. The three polymorphisms were genotyped in 260 CC patients, 212 CIN patients and 286 healthy controls in a hospital based case-control study in Western China. The three SNPs of RUNX3 were analyzed between every two groups. We found TT genotype of rs760805 (P=0.01, OR=0.55, 95% CI=0.35-0.88) compared with AA/AT genotype and AG genotype of rs2236852 (P=0.0024, OR=1.72, 95% CI=1.25-2.5) compared with AA/GG genotype were significantly associated with susceptibility to CC. The former was also associated with the clinical stage of CC. We also found SNPs rs760805 (P=0.0042, OR=8.33, 95% CI=1.12-50) and rs7528484 (P=0.027, OR=0.14, 95% CI=0.027-0.72) were closely connected with HPV infection in CIN patients. Moreover, we found rs2236852 AG genotype of RUNX3 was more related with the progression from CIN to CC (P<0.0001, OR=2.27, 95% CI=1.54-3.45). RUNX3 mRNA expression was significantly decreased in CC (P<0.0001) while no significant relationship between RUNX3 mRNA expression and the three SNPs. Those results probably mean that the SNPs of RUNX 3 influence not only the genetic susceptibility to CC, but also the pathogenesis of CC and CIN in Western China. The decreased expression of RUNX3 mRNA might indicate the inhibition of CC.