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To evaluate the effects of -1290AG, -1195GA and -765GC single nucleotide polymorphisms (SNPs) in the promoter of cyclooxygenase (COX)-2 gene on the risk of pathogenesis of pancreatic cancer.Peripheral blood samples were collected from 283 patients with pancreatic cancer and 566 normal controls. Questionnaire survey was conducted to understand the demographic data and status of smoking and smoking cessation of the subjects. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of the gene fragments containing the 3 SNP sites in the promoter regions of the COX-2 gene. Statistical tests were performed to analyze the relations among different factors and the risk of pancreatic cancer.Three SNPs, -1290AG, -1195GA, and -765GC were identified. A case-control analysis revealed 1.75-fold (95% CI = 1.16-2.64) and 2.53-fold (95% CI = 1.43-4.47) excesses of risks of developing pancreatic cancer for the -1195AA and -765CG genotype carriers respectively compared with the non-carriers. Compared with A(-1290)-G(-1195)-G(-765) containing haplotype, greater risks of developing pancreatic cancer were observed for A(-1290)-A(-1195)-G(-765), (OR = 1.26, 95%, CI = 1.02-1.56) and G(-1290)-A(-1195)-C(-765) (OR = 5.54, 95% CI = 1.79-17.16) containing haplotypes. There were interactions between the -765CG or -1195AA genotype and smoking in the risk of developing pancreatic cancer.The SNP of -1195AG and -765GC in the COX -2 promoter may play an important role in mediating hereditary susceptibility to developing pancreatic cancer.

The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signaling pathway has been shown to participate in tumorigenesis. We previously have shown that the FAS-1377G/A and FASL-844T/C polymorphisms are associated with esophageal cancer. This case-control study was to examine the contribution of the polymorphisms to susceptibility of colorectal cancer.PCR-RFLP method was used to determine the genotypes of FAS-1377G/A and FASL-844T/C in 382 patients with colorectal cancer and 648 controls. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression model.The subjects with the AA genotype of FAS-1377G/A and CC genotype of FASL-844T/C had an increased risk for colorectal cancer compared with those with the FAS-1377GG genotype (adjusted OR, 1.65; 95% CI, 1.14-2.38) and FASL-844TT genotype (adjusted OR, 1.76; 95% CI, 1.37-2.28). Furthermore, the effect of FAS and FASL polymorphisms on risk of colorectal cancer displayed a significantly gene-gene interaction (likelihood ratio test, P = 0.002).These findings suggest that the FAS-1377G/A and FASL-844T/C polymorphisms may be genetic susceptibility factors for colorectal cancer among Chinese population.

Nucleotide excision repair has been shown to have great impact on the sensitivity of tumors to platinum-based chemotherapy. This study was to examine the association between genetic polymorphisms in XPC and XPD, two important components in nucleotide excision repair system, and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer.Patients (n = 151) treated with platinum-based chemotherapy were genotyped for the AT dinucleotide insertion or deletion in intron 9 of XPC or Lys751Gln polymorphism in XPD. Clinical response to chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model and adjusted for sex, age, clinical stage, and regime of chemotherapy.The overall response rate to the chemotherapy (CR + PR) was 35.1%, with 1 CR, 52 PR, 75 SD, and 23 PD. It was found that patients with the XPC LL genotype had significantly higher response rate than patients with the XPC SS genotype (adjusted OR = 3.19, 95% CI = 1.11 - 9.17; P = 0.031). However, no association was found between the XPD Lys751Gln polymorphism and response to the chemotherapy. In addition, these two polymorphisms seemed to have synergic effect, with the OR being 2.90 (95% CI = 1.07 - 7.86) for patients carrying the XPC LL and XPD Lys/Lys genotypes compared with those carrying the XPC SS or SL and XPD Lys/Lys genotypes.These results suggest that genetic polymorphisms in nucleotide excision repair might be associated with clinical response to platinum-based chemotherapy.