title: 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: 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. 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 A18911C (Lys751Gln), XPF Arg415Gln, XPG Asp1104His, ERCC1 C118T]; homologous recombination repair [NBS1 Glu185Gln, Rad51 135G/C, XRCC3 C18067 (Thr241Met)]. 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. 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. (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.
authors.affiliation: Department of Genetics, Medical University of Wroclaw, Marcinkowskiego 1, 50-368, Wroclaw, Poland. justyna@gen.am.wroc.pl
authors.forename: Justyna
authors.initials: J
authors.lastname: Gil
authors.forename: Dave
authors.initials: D
authors.lastname: Ramsey
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Stembalska
authors.forename: Pawel
authors.initials: P
authors.lastname: Karpinski
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Pesz
authors.forename: Izabela
authors.initials: I
authors.lastname: Laczmanska
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Leszczynski
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Grzebieniak
authors.forename: Maria Malgorzata
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human