Association of single-nucleotide polymorphisms of high-mobility group box 1 with susceptibility and clinicopathological characteristics of uterine cervical neoplasia in Taiwanese women.

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.