HLA genes and other candidate genes involved in susceptibility for (pre)neoplastic cervical disease

This review focuses on common and genetic risk factors such as HLA and other genes that may be involved in susceptibility for (pre)neoplastic cervical disease. The goal of this review is the evaluation of polymorphisms that are either associated with cervical intraepithelial neoplasia (CIN) and/or cervical cancer. A pooled analysis was performed for DQA1, DQB1 and DRB1 alleles and 10 other genes that have been evaluated in more than one study. An association, either an increased or a decreased risk, with CIN and cervical cancer at a 5% significance level was found for 15 HLA II alleles. Four polymorphisms (Tp53, IL-10, CYP2D6 and the MTHFR) exhibited an increased CIN and cervical cancer risk. However, only the pooled analysis of the DQB1 alleles, the HLA-DR specificities and Tp53 genes had sufficiently large sample sizes to confirm or exclude the proposed association. Our data indicate that further analysis in larger sample sizes, especially for genes other than the HLA genes, is neccesary to describe the exact relations between these genes and susceptibility for CIN and cervical cancer with an adequate power.