Contribution of retinoblastoma LOH and the p53 Arg/Pro polymorphism to cervical cancer

Epidemiological studies indicate that infections by certain types of humanpapillomaviruses (HPVs) are causally linked to the development of cervical cancer.It is also known that HPV infections alone do not cause progression to cervicalcancer, as additional genetic changes such as loss of distinct chromosomal regions,inactivation of tumor-suppressor genes and activation of oncogenes must also occurin order for malignant transformation to take place. In the present study, 78patients diagnosed with cervical cancer and 36 cervical cancer-free cases (control)were analyzed for high-risk HPV genotypes (16 and 18) by polymerase chain reaction(PCR). Loss of heterozygosity (LOH) of the retinoblastoma gene (Rb) at two polymorphicintronic sites (intron 1 and 17) and the p53 polymorphism in codon 72 were detectedby RFLP and allele-specific PCR, respectively. HPV 16 and 18 were found at frequenciesof 93.6 and 8.3% in the cervical cancer and control samples, respectively. LOHwas detected in 63% of patients in intron 1 and/or intron 17. p53 allele frequencyfor Arg/Arg was 43.6% (34/78), for Arg/Pro 37.2% (29/78) and for Pro/Pro 19.2%(15/78). The relative risk (RR) of LOH and Arg/Arg alone was 1.7 and 1.1, respectively,while the combined RR for Rb LOH and p53 Arg/Arg was 2.5. The present study showeda significant association of the chromosomal allelic loss of Rb in Sudanese cervicalcancer patients, while no such association was observed with other parameters,such as clinical stage and degree of differentiation; hence, it cannot be a determinantof tumor behavior in cervical carcinoma. Although the p53 arginine allele is itselfan important risk factor for cervical cancer, the combined risk with LOH of Rb,which appears to be greater, might indicate a possible epistatic effect of thetwo genes/polymorphisms.