Ala499Val (C > T) and Lys939Gln (A > C) polymorphisms of the XPC gene: their correlation with the risk of primary gallbladder adenocarcinoma--a case-control study in China

Abstract

Genetic variations in the gene XPC may be associated with increased risk for gallbladder cancer (GBC). In this study, we detected two non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) in 334 cases of GBC and 329 subjects of hospital-based age- and sex frequency-matched controls in China using a polymerase chain reaction-restriction fragment length polymorphism assay. Allelic association analysis for the two single-nucleotide polymorphisms (SNPs) showed that the risk allele T of Ala499Val was significantly associated with GBC [odds ratio (OR)=1.40, 95% confidence interval (CI): 1.11-1.76, P=0.005), with a population attributive risk of 5.3%. Logistic regression analysis revealed that Ala499Val CT heterozygote (OR=1.56, 95% CI: 1.13-2.14, P=0.002) and TT homozygote (OR=1.93, 95% CI: 1.04-3.55, P=0.048) had a significantly increased risk compared with CC homozygotes. Genetic analysis suggested that either the SNPs directly exert an effect or the linked functional gene impact of the disease trait likely follows an additive or dominant model. Gene interaction analysis demonstrated that the effects of XPC diplotypes (defined as the number of risk genotypes at the two SNP loci) were highly dependent on gallstone. The data from this case-control study indicated that XPC exonic variants contributed to the risk of GBC in this Chinese population.

Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy

“…Regarding these genes, previous studies [36,37] mostly focussed on their respective SNP which were high risk for developing cancer and only few articles [38] in the literature compared them with the outcome of chemotherapy in NSCLC. For the RRM1 SNPs, study [38] showed that patients harboring the A(−)37C genotype had a longer PFS with gemcitabine-based chemotherapy than patients with A(−)37A and C(−)37C.…”

Single nucleotide polymorphisms in DNA repair genes and putative cancer risk

“…An increased risk for developing bladder cancer was found for variant alleles 499Val and 939Gln (Qiu et al 2008;Rouissi et al 2011;Sak et al 2006;Sanyal et al 2004). The variant 499Val was also connected to an increased risk of gall bladder cancer, while in this case the variant form of Lys939Gln does not seem to be a risk factor (Jiao et al 2011). No significant association between 939Gln and cancer was also observed for colorectal cancer (Gil et al 2012).…”

Molecular biology of gallbladder cancer: Potential clinical implications

“…Many other molecular markers, proteins and factors, including PIK3CA,[52], methylation,[5354] protein gene product 9.5,[55] proteomics,[56] Raf-1,[57] RASSF1A,[58] Reg IV,[59] Rsf-1,[60] Survivin,[61] Syndecan-1,[62] Synuclein-gamma,[63] TAG-72,[64] Telomeres,[65] Telomerase activity (hTERT),[66] TEM8,[67] Thrombospondin,[68] Thymidine phosphorylase,[69] Angiogenesis,[70] TNF-alpha,[71] TLRs,[72] Topoisomerase,[73] Vasculogenic mimicry,[74] VEGFs,[75–77] and XPC[78] are involved in the development or progress of GBC. Some of these directly exert an effect on clinical outcome, while some link with development or of GBC.…”