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Genetic polymorphisms of  NEIL1  and  NEIL2  maybe change protein function, and increased carcinogenesis. In this study, seven  NEIL1  SNPs and three  NEIL2  SNPs were selected. 400 CSCCs, 400 CIN III, and 1200 normal healthy controls were genotyped by mismatch amplification PCR. mRNA and protein expression of  NEIL 2 was measured in 92 freshly-obtained CSCC tumor tissues. The association between homozygote CC genotype of  NEIL2  rs804270 with susceptible risk was gradually increased in CIN III (OR = 1.44) and CSCC (OR = 2.22). Carriers of C-allele (GC + CC) at rs804270 had a high risk of CSCC (OR = 1.46). The heterozygote GT genotype of rs8191664 was also closely related to the higher risk of CINIII (OR = 1.59) and CSCC (OR = 2.54). Carriers of T-allele (GT + TT) at rs8191664 had a high risk for CIN III (OR = 1.55) and CSCC (OR = 2.34). The genotypes of  NEIL2  rs804270 (G/C) and rs8191664 (G/T) that were related to the higher risk for CIN III were CC-GG (OR = 1.42) and CC-GT (OR = 2.07). More notably, there was a greater risk for CSCC with the GC-GT (OR = 1.91), CC-GG (OR = 1.67), and CC-GT (OR = 6.18) genotypes.  NEIL2  mRNA expression in CSCCs with the rs804270-CC genotype was lower expression than those in CSCCs with the rs804270-GG and rs804270-GC genotypes. Similarly,  NEIL 2 protein expression was significantly decreased in CSCCs with the rs804270-CC genotype. In summary, the two genetic polymorphisms (rs804270 and rs8191664) of  NEIL 2 gene were significantly associated to the increased susceptibility of CIN III or CSCC. This increased susceptibility maybe due to altered  NEIL 2 repair activity through altered protein expression, or changed structure of the functional domain. The genotypes of GC-GT, CC-GG, and CC-GT of rs804270 and rs8191664 of  NEIL2  gene could act as a genetic predictive biomarker of susceptibility to CIN III and CSCC.

Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker