TITLE:
Detection of Polymorphisms of DNA Repair Genes (XRCC1 and XPC) in Prostate Cancer
AUTHORS:
Amani Fouad Sorour, Iman Mamdouh Talaat, Tamer Mohammed Abou Youssif, Mohamed Adel Atta
KEYWORDS:
Prostate Cancer; Polymorphisms; PCR; XRCC1; XPC
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.10,
December
25,
2013
ABSTRACT:
Prostate cancer is a common disease
with a multifactorial and complex etiology. It is the most common male malignancy
and the second leading cause of death in many countries. The widespread use of
PSA testing has increased the detection of this cancer at earlier stages,
although this diagnostic method has proved to be insufficient to identify the
disease. DNA in most cells is regularly damaged by endogenous and exogenous
mutagens. At least four main partially overlapping damage repair pathways
operate in mammals. Common polymorphisms in DNA repair genes may alter protein
function and an individual’s capacity to repair damaged DNA; deficits in repair
capacity may lead to genetic instability and carcinogenesis. In the present
study, we investigated the genotypic distribution of XRCC1 and XPC polymorphisms
and its association with prostate cancer risk, pathological staging and
Gleason’s scoring. The present study was conducted in the departments of
Clinical Pathology, Pathology, and Urology Faculty of Medicine, Alexandria University-Egypt.
A total number of 50 patients with pathologically confirmed prostate cancer and
50 age-matched control subjects were enrolled in this study. The diagnosis was
made on the basis of histopathological findings, following radical
prostatectomy or transurethral resection of the prostate (TURP). Genomic DNA
was extracted from peripheral blood using QIAamp blood DNA isolation kits. PCR
followed by enzymatic digestion of the PCR products for (XRCC1, XPC) was used
for the genotyping of these polymorphisms. Statistical analyses were performed
using SPSS statistics version
20. The genotype frequencies of the studied polymorphisms in all the samples (n = 100), PC patients (n = 50) and healthy controls (n = 50) were consistent with the
Hardy-Weinberg equilibrium distribution (p-value > 0.05). There was no
statistical difference in the genotypes of the XRCC1 Arg399Gln and XPC
Lys939Gln between cases and controls. The “Gln” allele frequency of XPC
Lys939Gln as well as the “Gln” allele frequency of XRCC1 Arg399Gln tended to be
lower in controls than in PC patients. Yet, these decreases were not
statistically significant. We also examined the combined effect of XPC and
XRCC1 and we found a decreased PC risk when XPC 939 Lys/Lys + Lys/Gln and XRCC1
399 Arg/Arg + Arg/Gln are combined (OR = 0.370, 95% CI = 0.142 - 0.962).