Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population

Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorphisms in XP genes may be associated with a change in DNA repair capacity, which could be associated with colorectal cancer development. We assessed the association between 94 single nucleotide polymorphisms (SNPs) within seven XP genes (XPA–XPG) and the colorectal cancer risk in the Polish population. We genotyped 758 unselected patients with colorectal cancer and 1,841 healthy adults. We found that a significantly decreased risk of colorectal cancer was associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p < 0.0001) and the rs2228000_TT genotype (OR 0.29; p < 0.0001) compared to the reference genotype (CC). And an increased disease risk was associated with the XPD SNP, rs1799793_AG genotype (OR 1.44, p = 0.018) and rs1799793_AA genotype (OR 3.31, p < 0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD and XPG revealed haplotypes associated with an altered colorectal cancer risk. Stratified analysis by gender showed differences between the association of three SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males. Association analysis between age of disease onset and polymorphisms in XPD (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these variants in patients under and over 50 years of age. Our results confirmed that polymorphisms in XPC and XPD may be associated with the risk of colorectal cancer.

Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

“…The results from three studies were similar to ours [25,28,29]. Interestingly, Steck et al [28] reported a significantly positive association between this polymorphism and CRC risk in African Americans, while another study demonstrated an association in the reverse direction in Caucasians [27]. Several meta-analyses on the association between these two polymorphisms and CRC risk have been published [8,10,31].…”

“…When compared with the XPC rs2228001 A > C polymorphism, relatively fewer studies have examined the association of the rs2228000 C > T polymorphism with CRC susceptibility [25,27,28,29]. The results from three studies were similar to ours [25,28,29].…”

“…A number of case-control studies have been carried out to investigate the association between XPC rs2228001 A > C polymorphism and the risk of CRC among Caucasians [22,23,24,25,26,27,28]. Despite biological plausibility, none of those investigations provided evidence of the association of this polymorphism with CRC susceptibility [22,23,24,25,26,27,28]. Several studies have also evaluated the role of XPC rs2228001 A > C polymorphism in CRC among Asians [11,12,29,30].…”

Association between XPG gene polymorphisms and development of gastric cancer risk in a Chinese population

“…Previous studies have reported that XPG gene polymorphisms are associated with different kinds of cancers (Liu et al, 2014;Mirecka et al, 2014;Steck et al, 2014;Xu et al, 2014;Paszkowska-Szczur et al, 2015). In this paper, we conducted a casecontrol study to investigate the role of three common single nucleotide polymorphisms (SNPs) in the XPG gene (rs2094258, rs751402 and rs17655) in the development of gastric cancer in a Chinese population.…”

Farmacogenética, tabaco, alcohol y su efecto sobre el riesgo de desarrollar cáncer

“…Los polimorfismos gené-ticos de las enzimas implicadas en estos procesos de reparación van a determinar su capacidad funcional, pudiendo conducir a una menor capacidad de reparación del ADN, que puede ser la base de una tasa de mutación más alta, y como consecuencia última provocar un aumento de riesgo de desarrollo de procesos tumorales [33][34][35] . Los polimorfismos en ERCC1 y ERCC2 han sido asociados a un mayor riesgo para el desarrollo de cáncer de piel, cáncer de mama y cáncer colorectal [36][37][38][39][40] .…”