| Abstrakt: |
This study was undertaken to understand the role of an important polymorphism at codon 72, exon 4 of tumor suppressor gene TP53 which encodes a nuclear protein and prevents the cells from dividing before DNA damage is repaired. Presence of homozygous arginine allele at codon 72 considered is a risk factor for cancer. The objective of present study was to determine the frequency of codon 72 polymorphism of TP53 gene in sporadic breast cancer patients and those with genetic lineage. One hundred and fifty female patients with sporadic breast cancer were included in this study, of these, one hundred female patients were recruited at Shaukat Khartum Memorial Cancer Hospital & Research Center, Lahore and fifty patients were recruited at Mayo Hospital Lahore Pakistan, from January 2005- December 2008. The median age of the patients was 40 years (range 18-65). From all the participant patients three type of samples viz. blood, normal and tumor tissue were collected. Besides the sporadic breast cancer patients, three families, two from Lahore and one from Multan were also included in the study. Out of these families, one family was detected for Li-Fraumeni syndrome like characteristics. Blood samples were collected from normal persons and families. Fifty normal females belonging to different areas of Pakistan, ranging from 18-65 years of age were also included in this study for comparison purpose. Genomic DNA was amplified in PCR reaction, which was then subjected to Restriction Fragment Length Polymorphism (RFLP) analysis. Proline allele was found to be more dominant compared to arginine allele. RFLP analysis showed that arg/pro (53%) and pro/pro (35%) genotypes were more significant in Pakistani breast cancer patients compared to arg/arg (I 2%) genotype. Similar type of genotypic prevalence was found in normal control samples. The arg/pro and pro/pro alleles were also prominent in familial breast cancer patients. Contrary to arg allele which is usually implicated with breast cancer development in western countries, the pro allele in the present study was more prominent in Pakistani sporadic breast cancer patients, normal subjects and those of genetic lineage. Frequency of pro allele codon 72 of TP53 in female breast cancer patients of Pakistan may be due to specific geographical reasons. [ABSTRACT FROM AUTHOR] |
