No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the risk of colorectal cancer in West Algerian population: a case–control study

Abstract

Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic and environmental factors both seem to play a part. Many epidemiological studies have explored the association between genetic polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD) lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various populations; however, the results are controversial. We conducted this case-control study in a West Algerian population to assess the potential role of this genetic polymorphism on the risk of CRC in this population. Genomic DNA was extracted from blood samples collected from 129 sporadic CRC patients and 148 normal controls. The polymorphisms were determined by pyrosequencing technique. The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls did not differ significantly from those predicted by the Hardy-Weinberg distribution (p > 0.05). There were no significant differences in the genotypes distribution and allele frequencies between CRC patients and controls. A significant association was found between the combined heterozygous of XRCC3 and homozygous variant of XPD gene and CRC. This is the first study on DNA repair genetic polymorphisms in West Algerian population, and it suggests that the XRCC3 Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk in this population.

<p>Association of <em>XRCC1</em>, <em>XRCC2</em> and <em>XRCC3</em> Gene Polymorphism with Esophageal Cancer Risk</p>

“…90 From Indian subcontinent, two populations practicing consanguineous marriages reported an association with increased risk, for colorectal cancer in Kashmiri population 50 and breast cancer in Pakistani population. 91 For XRCC3 p.Thr241Met polymorphism, no association was reported with gastric cancer in Italian population 92 and with colorectal cancer in the West Algerian population 93 but an association with an increased risk was reported for lung cancer in an Italian population, 23 oral SCC in Thai population, 94 and gastric cancer in the Chinese population. 95 On the other hand, a protective role of CT and TT genotype has been reported in colorectal cancer in Polish population 96 and Basal cell carcinoma of the skin in population from Hungary, Romania and Slovakia.…”

Meta-analysis of the relationship between XRCC3 T241M polymorphism and colorectal cancer susceptibility

“…Subgroup analysis results showed that the XRCC3 T241M polymorphism was not associated with CRC risk both in Asians and in Caucasians. There was only one study of Africans, and thus further studies examining Africans should be conducted (Moghtit et al, 2014). Stratification by sample size (> 500) for subgroup analysis revealed no significant association, indicating there was no smallstudy bias in our meta-analysis.…”

“…Recently, numerous studies have examined the association between the XRCC3 T241M polymorphism and CRC. However, the results are inconsistent, likely because these studies were single case-control studies including small sample sizes (Moghtit et al, 2014). To clarify these inconsistent findings, we conducted this meta-analysis to obtain more reliable results by combining a larger number eligible studies, increasing the sample size, and conducting subgroup analysis.…”

“…Base on the inclusion criteria, 13 case-control studies with full-text were included in this meta-analysis (Krupa and Blasiak, 2004;Jin et al, 2005;Moreno et al, 2006;Skjelbred et al, 2006;Yeh et al, 2007;Improta et al, 2008;Pardini et al, 2008;Curtin et al, 2009;Canbay et al, 2011;Gil et al, 2012;Zhao et al, 2012;Mucha et al, 2013;Moghtit et al, 2014). The flow chart outlining the criteria used for study selection is shown in Figure 1.…”

“…Among the 13 casecontrol studies, there were 8 studies of Caucasians (Krupa and Blasiak, 2004;Skjelbred et al, 2006;Improta et al, 2008;Pardini et al, 2008;Curtin et al, 2009;Canbay et al, 2011;Gil et al, 2012;Mucha et al, 2013) and 5 studies of Asians (Jin et al, 2005;Moreno et al, 2006;Yeh et al, 2007;Zhao et al, 2012;Moghtit et al, 2014). Nine studies were consistent with HWE for the genotype distribution of the controls (Moreno et al, 2006;Skjelbred et al, 2006;Yeh et al, 2007;Improta et al, 2008;Pardini et al, 2008;Curtin et al, 2009;Gil et al, 2012;Mucha et al, 2013;Moghtit et al, 2014), while 4 were not (Krupa and Blasiak, 2004;Jin et al, 2005;Canbay et al, 2011;Zhao et al, 2012). The baseline characteristics and methodological quality of all studies included are summarized in Table 1.…”