Detection of Polymorphisms of DNA Repair Genes (XRCC1 and XPC) in Prostate Cancer

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).

XPC exon15 Lys939Gln variant increase susceptibility to prostate adenocarcinoma

“…[ 16 ] However, another study indicated no significant difference in the XPC Lys939Gln genotypes of PA participants and control subjects in Egyptian populations. [ 21 ] In 2013, He et al carried out a meta-analysis and demonstrated an elevated colorectal, lung, and bladder cancer susceptibility associated with this variant, especially in Asian population. [ 34 ] Two years later, another study showed no statistical difference between XPC Lys939Gln polymorphism and PA risk.…”

Effects of Xeroderma pigmentosum group C polymorphism on the likelihood of prostate cancer

“…A Japanese population‐based research showed that the XPC rs2228001 A/C polymorphism might be a risk factor for PCa 17 . However, another study based on Egyptian population suggested no significant difference between the XPC rs2228001 A/C variant and PCa susceptibility 22 . In 2013, a meta‐analysis conducted by He et al indicated elevated colorectal, lung, and bladder cancer susceptibility correlated with this polymorphism 33 .…”

“…31,32 Previous case-controlled studies were conducted to investigate whether the XPC rs2228001 A/C polymorphism confers the risk of PCa, but with controversial results. [17][18][19][20][21][22][23] A Japanese population-based research showed that the XPC rs2228001 A/C polymorphism might be a risk factor for PCa. 17 However, another study based on Egyptian population suggested no significant difference between the XPC rs2228001 A/C variant and PCa susceptibility.…”

“…However, there are vague conclusions about the relationship between XPC rs2228001 A/C polymorphism and PCa susceptibility in different case‐controlled studies. Hence, a systematic analysis based on all eligible studies was conducted to further investigate the correlation between the XPC rs2228001 A/C polymorphism and PCa risk 17‐28 …”

“…Hence, a systematic analysis based on all eligible studies was conducted to further investigate the correlation between the XPC rs2228001 A/C polymorphism and PCa risk. [17][18][19][20][21][22][23][24][25][26][27][28]…”