Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer

Human papillomaviruses type 16 and 18 are the major cause of cervical cancer. However, genetic factors contribute to the propensity of persistent HPV infection and cervical carcinoma. Allelic variants of the human leukocyte genes have shown to be associated with cervical neoplasia. The strongest associations have been found with the genes in the HLA class II region. The aim of this study was to analyze the association of two non-HLA class II markers with invasive cervical cancer. Microsatellite polymorphism of the TNFA gene located in the class III region and a short tandem repeat polymorphism of the MICA gene located in the centromeric end of the HLA class I region were analyzed. Eighty-five patients and 120 matched control individuals from a population-based cohort from Northern Sweden participated in this nested case-control study. MICA was not associated with cervical carcinoma. TNFa-11 frequency was increased in the HPV18 DNA positive patients (OR = 2.84, p = 0.0481, CI = 1.04-7.78, pc = NS). TNFa-11 was not associated with susceptibility to HPV16 infection, but it increased the risk for cervical cancer with the HLA DQ6 (DQA 1*0102-DQB 1*0602) haplotype. Our findings indicate that the association of TNFA with cervical cancer is different with CIN. The extended HLA DQ6-TNFa-11 haplotype is increasing the risk for development of cervical cancer significantly (OR = 3.08, p = 0.0104, CI = 1.30-7.31).