The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

Abstract

Abstract:Background: Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors.Aim: we focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911CMaterial and methods: The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used.Results: We found that: i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391,3.7782) p=0.038], ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215,0,9131) p=0.031] for an individual with at least one A allele at this locus. Conclusions:1. the XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer.2. the NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Four publications were excluded because of meta-analysis, control group had cancer patients or not published in English. Finally, 26 full-text articles with eligibility were included in this meta-analysis (Smith et al, 2003;Huang et al, 2006;Mechanic et al, 2006;Moreno et al, 2006;Crew et al, 2007;Jorgensen et al, 2007;Chang et al, 2008;Hung et al, 2008;McWilliams et al, 2008;Rajaraman et al, 2008;Abbasi et al, 2009;Han et al, 2009;Joshi et al, 2009;Agalliu et al, 2010;Rajaraman et al, 2010;Doherty et al, 2011;Krupa et al, 2011;Smith et al, 2011;Gil et al, 2012;Yu et al, 2012;Cheng et al, 2013;Santos et al, 2013;Wang et al, 2013;Wyss et al, 2013;Kohlhase et al, 2014;Steck et al, 2014). The flow chart which reflected the details of article selection was presented in Figure 1.…”

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

“…Associations between six single-nucleotide polymorphisms (SNPs) of the earlier-mentioned five genes and CRC have been reported in different ethnic groups (Smith et al, 2001;Landi et al, 2003Landi et al, , 2005Krzesniak et al, 2004;Jiang et al, 2005;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Berndt et al, 2006;Huang et al, 2006;Koh et al, 2006;Kuriki et al, 2006;Matsuo et al, 2006;Moreno et al, 2006;Theodoropoulos et al, 2006;Tranah et al, 2006;Hansen et al, 2007;Kang et al, 2007;Stern et al, 2007;Vogel et al, 2007;Yin et al, 2007;Kury et al, 2008;Funke et al, 2009;Khatami et al, 2009;Tsilidis et al, 2009;Yang et al, 2009;Engin et al, 2010;Meplan et al, 2010;Loh et al, 2011;Wu et al, 2011;Crous-Bou et al, 2012;Gil et al, 2012). These six variants comprised rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, rs4880 of SOD2, rs2228001 of XPC, and rs1801282 of PPARG.…”

Association of Thr241Met polymorphism of XRCC3 gene with risk of colorectal cancer in the Polish population

“…However, in a subsequent study the same authors observed a lack of Thr241Met polymorphism impact on CRC risk [27]. A similar conclusion follows from the Gil et al investigation which found no statistical association in groups consisting of 133 CRC patients and 100 controls [28].…”