ABSTRACT
The aim of this report is to determine frequencies and associations of p53 codon 72 arg/pro polymorphism with different types of cancer in Sudan. p53 codon72 arg/pro polymorphism distribution and allele frequencies in 264 samples of different types of cancers were investigated using PCR. The results were compared to 235 normal controls. The results indicated significant differences in frequency and genotype association between different types of cancers. Breast carcinoma patients most prominently showed excess of homozygous arg genotype as compared to controls with an Odd ratio (OR) of 19.44, 95 %CI: 6.6-78.3, P < 0.0001. Less prominently cervical cancer showed genotype effect of 2.4 OR, 95 %CI: 1.12-5.33, P = 0.015, while esophageal cancer had an OR of 0.57, 95 %CI: 0.23-1.42, P = 0.1. In Burkitt's lymphoma, however, in contrast the homozygous arg accounted for only 6.9 %, (OR 0.18, 95 %CI: 0.02-0.89, P = 0.018). We concluded that p53 arg/pro polymorphism has different pattern of frequency in different types of cancer among Sudanese patients, indicating perhaps different etiology and biology of these tumours.
Subject(s)
Amino Acid Substitution/genetics , Codon/genetics , Genetic Predisposition to Disease , Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Confidence Intervals , Female , Gene Frequency/genetics , Humans , Male , Middle Aged , Odds Ratio , Sudan , Young AdultABSTRACT
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.
