An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection

Our recent report indicated that HPV infection may be associated with an increased frequency of p161NK4a promoter hypertmethylation to cause p 16 inactivation. In this study, we further speculated that the HPV infection may be linked with the expression of DNA methyltransferase (DNMT) protein in lung cancer patients and it was observed that an association of p161NK4a promoter hypermethylation with HPV infection existed, but only in female cases (P < 0.0001). Interestingly, DNMT3b protein expression was significantly correlated with p161NK4a promoter hypertmethylation (P=0.023) and HPV 16/18 infections (P < 0.001), respectively. Moreover, the correlation between p161NK4a promoter hypermethylation and DNMT3b protein expression was exclusively seen in female cases (P=0.035). These results strongly suggested that the involvement of HPV infection in nonsmoking female lung tumorigenesis may be mediated, at least to a certain extent, through the increase of DNMT3b protein expression to cause p161NK4a promoter hypermethylation. (c) 2005 Elsevier Ireland Ltd. All rights reserved.