Contribution of retinoblastoma LOH and the p53 Arg/Pro polymorphism             to cervical cancer.
Epidemiological studies indicate that infections by certain types of human             papillomaviruses (HPVs) are causally linked to the development of cervical cancer.             It is also known that HPV infections alone do not cause progression to cervical             cancer, as additional genetic changes such as loss of distinct chromosomal regions,             inactivation of tumor-suppressor genes and activation of oncogenes must also occur             in order for malignant transformation to take place. In the present study, 78             patients 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 polymorphic             intronic sites (intron 1 and 17) and the p53 polymorphism in codon 72 were detected             by RFLP and allele-specific PCR, respectively. HPV 16 and 18 were found at frequencies             of 93.6 and 8.3% in the cervical cancer and control samples, respectively. LOH             was detected in 63% of patients in intron 1 and/or intron 17. p53 allele frequency             for 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 showed             a significant association of the chromosomal allelic loss of Rb in Sudanese cervical             cancer patients, while no such association was observed with other parameters,             such as clinical stage and degree of differentiation; hence, it cannot be a determinant             of tumor behavior in cervical carcinoma. Although the p53 arginine allele is itself             an 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 the             two genes/polymorphisms.
Department of Molecular Biology, Institute of Endemic Diseases,                     University of Khartoum, Medical Campus, Khartoum, Sudan.
Huda A
HA
Eltahir
Ahmed M
AM
Elhassan
Muntaser E
ME
Ibrahim
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53