CASP8 Promoter Polymorphism is Associated With High-Risk HPV types and Abnormal Cytology but not With Cervical Cancer

Only a small fraction of women infected with human papillonnavirus (HPV) progress to cervical cancer pointing to additional risk factors including host genetics that might play a role in development of cervical cancer. Caspase-8 (encoded by CASP8gene) is crucial in generating cell death signals to eliminate potentially malignant cells. Genetic variation in CASP8 might influence the susceptibility to cancer. CASP8 -652 6N ins/del polymorphism has been previously reported to influence the progression to several cancers including cervical cancer. This polymorphism was investigated in 445 women of black African and Mixed Ancestry origin with invasive cervical cancer and 1,221 controls matched (1:3) by age, ethnicity, and domicile status. Genotyping for CASP8 -652 6N ins/del was done by PCR-RFLP. In the control women cervical disease was detected by cervical cytology. The CASP8 -652 6N del/del genotype did not show any significant association (P = 0.948) with cervical cancer. Further analysis within the controls showed a weak association (P = 0.048) of this polymorphism with abnormal cytology in both ethnicities and high-risk HPV infection (P = 0.030) only in the black Africans. This is the first study of the role of CASP8 -652 6N ins/del polymorphism in cervical cancer in an African population. These results show that CASP8 -652 6N del/del genotype increases the risk of abnormal cytology and high-risk HPV infection but does not show an association with cervical cancer. This result points towards an important role of CASP8 in HPV infection and in the development of pre-cancers. J. Med. Virol 83:630-636, 2011. (C) 2011 Wiley-Liss, Inc.