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This study investigated the association between a missense SNP in the codon of ADD1 phosphorylation site and the susceptibility of non-cardia gastric cancer in a Chinese population.PhosphoSitePlus and dbSNP database were combined to discover missense SNPs in the codon of phosphorylation site. Then, we genotyped the missense SNP in 1, 998 cases with non-cardia gastric cancer and 2, 008 cancer-free controls of Chinese descent. Analysis was conducted by using Logistic model adjusted by gender and age.The rs4963 in the codon of ADD1 phosphorylation site was found. The frequencies of the 3 rs4963 genotypes, CC, CG, GG, among controls were 25.2%, 50.4%, and 24.4%, respectively, among patients were 20.1%, 50.6%, and 29.3%, respectively. Compared with CC genotype, the rs4963 CG genotype and GG genotype significantly increased the risk of non-cardia gastric cancer with the odds ratios being 1.24 (95%CI: 1.06 ∼ 1.46, P = 0.008) and 1.49 (95%CI: 1.25 ∼ 1.78, P0.001), respectively.Fnnctional polymorphism in the phosphorylation site of ADD1 (rs4963) may influence the susceptibility of non-cardia gastric cancer.

The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).Four hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model.A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea.The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.

To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors.The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction.Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001).HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer.

To investigate the association between CTLA-4 +49A/G polymorphisms and the risk of susceptibility to cervical cancer.A hospital-based case-control study was conducted. 314 cases with primary cervical cancer and 320 healthy controls were collected and genotyped by PCR-based RFLP for +49A/G polymorphisms in the CTLA-4 gene.The A allele and AA genotype of CTLA-4 gene were 32.5% and 9.6% in the patients, and 25.8% and 5.6% in the controls, respectively. Subjects with CTLA-4 +49AA genotype conferred a higher risk of cervical cancer (OR = 2.06, 95%CI: 1.10 - 3.85; P = 0.024). However, the correlation between AA genotype in CTLA-4 polymorphisms and clinicopathological characteristics was not significant.The results of this study suggest that CTLA4 gene is associated with cervical cancer risk and may be a susceptible gene of cervical cancer.

To evaluate the association between polymorphism of transforming growth factor-β1 (TGF-β1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients.The genotype of TGF-β1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox-regression analyses.Among 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-β1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-β1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-β1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively).These results suggest that TGF-β1-509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients.

Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.

The Bcl-2 associated X protein (Bax), belonging to the Bcl-2 family, plays a pivotal role in mitochondria-dependent apoptosis. The aims of this study are to revalidate the functional significance of Bax G(-248)A polymorphism, and investigate its association with lung cancer risk in Chinese population.The biological function of Bax G(-248)A was tested by luciferase assays, and its effects on lung cancer risk was determined by case-control analysis of 989 patients with lung cancer and 990 controls.Bax -248A allele exhibited significantly higher transcriptional activity compared with G allele. The Bax-248A allele carriers yielded a significantly decreased risk of lung cancer, compared with -248G allele carriers (OR = 0.68, 95% CI = 0.48 approximately 0.90, P = 0.01). Furthermore, a significant gene-smoking interaction between Bax G(-248)A polymorphism and smoking existed among the light smokers.Bax G(-248)A polymorphism is associated with lung cancer susceptibility in Chinese population.

To investigate the frequencies of alleles and the association with risk of esophageal cancer in a Mongolian population, and to compare the allele frequencies of these polymorphisms between the two populations and the susceptibility to esophageal cancer.A case-control study was conducted, and 8 single nucleotide polymorphisms (SNP), including FAS - 670G/A, FAS - 1377G/A, FASL -844T/C, COX-2 - 1290A/G, COX-2 - 1195G/A, STK15 Phe31Ile, MMP-2 - 1306C/T and MMP -2 -735C/T, were detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 188 esophageal cancer cases and 324 normal controls of Mongolian. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. The results were then compared with the reported data of the Han ethnic Chinese population.In Mongolian, as compared with the STK15 31Ile/Ile genotype, the STK15 31Phe/Phe genotype carriers had an increased risk of esophageal cancer (adjusted OR = 2.20, 95% CI: 1.12-4.31), and the subjects with MMP-2 - 735TT genotype had an increased risk of esophageal cancer as compared with those with the MMP-2 - 735CC genotype (adjusted OR =4.82, 95% CI: 1.59 - 14.60). However, the rest of SNPs were not associated with the susceptibility to esophageal cancer. The allele frequencies of FASL - 844 T/C [0.264(171/648)/0.736 (477/648), 0.323(418/1296)/0.677(878/1296)], COX-2 - 1195G/A [0.431(279/648)/0.569(369/ 648), 0.492(1250/2540)/0.508(1290/2540)], MMP-2 - 1306C/T [0.869(563/648)/0.131(85/ 648), 0.835(1298/1554)/0.165(256/1554)] and MMP-2 - 735C/T [0.789(511/648)/0.211(137/ 648), 0.748(1163/1554)/0.252(391/1554)] were significantly different between the ethnic populations (chi2 = 7.03, 7.84, 3.94, 4.05, respectively, P0.05).These findings suggested that STK15 Phe31Ile and MMP-2 -735C/T polymorphisms might be the genetic susceptibility factors for esophageal cancer in Mongolian and there should be some differences of genetic susceptibility to esophageal cancer in between Han ethnic Chinese and Mongolian population.

To investigate the association between apoptosis genes Fas/Fas L promoter polymorphisms and the risk of the development of cervical cancer.Blood samples were collected from 314 cases with primary cervical cancer and 615 healthy controls. Genotypes of Fas/Fas L genes were determined by polymerase chain reaction-based restriction fragment length polymorphism. The associations with the risk of cervical cancer and impact of clinicopathological characteristics were estimated by logistic regression.Fas L-844CC genotype was significantly associated with increased risk of cervical cancer compared with Fas L-844TC or -TT genotype (OR = 3.05; P0.01). However, there was no significant difference of Fas-670A/G or -1377G/A genotypes. Interaction of genetic polymorphism between Fas and Fas L was observed. Stratification analysis revealed that Fas-670G or -1377A allele was significantly higher in squamous carcinoma in situ (OR = 1.77 or 1.93; P0.05) while Fas L-844CC genotype had an increased risk of invasive squamous carcinoma compared with that of Fas L-844TT genotype (OR = 3.33; P0.01). No significant associations were observed between polymorphisms in Fas/Fas L and clinical FIGO stage, cell differentiation, size of tumors, serum squamous cell carcinoma antigen value at the diagnosis and so on.The results of this study suggest that genetic polymorphisms of Fas and Fas L in apoptotic pathway are associated with the risk of development of cervical carcinoma.

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.

This study examined whether the two polymorphisms of GPX1 (198Pro--Leu) and TXNRD2 (370Lys--Arg) contributed alone or in combination, to the risk of gastric cancer development.A total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model.GPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P0.001) as compared with the risk genotype.The GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.

The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage or oncogene activation. Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein. We have previously shown that genetic polymorphisms in the MDM2 promoter (309T --G) and p53 coding region (72Arg --Pro) are associated with susceptibility to esophageal and lung cancers. This study investigated the associations between these polymorphisms in p53 and MDM2 and risk of the occurrence and progression of colorectal cancer.Genotypes of 1000 Chinese colorectal cancer patients and 1300 controls were determined by PCR-based restriction fragment length polymorphism or tetra-primer amplification refractory mutation system-PCR. Associations with risk of colorectal cancer were estimated by unconditional logistic regression.An increased colorectal cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.62-2.62] or TG (OR = 1.31, 95% CI = 1.06-1.62) genotype was observed compared with the TT genotype. No association was found between p53 polymorphism and risk of the cancer, with the ORs being 0.87 (95% CI = 0.68-1.11) for the Pro/Pro and 0. 85 (95% CI = 0.70-1.04) for the Arg/Pro genotype compared with the Arg/Arg genotype. However, combined analysis of MDM2 and p53 polymorphisms showed that compared with subjects carrying both MDM2 TT and p53 Arg/Arg genotypes, the OR for subjects carrying both MDM2 GG and p53 Pro/Pro genotypes was 2.75 (95% CI = 1.60-4.70), significantly higher than that for subjects carrying both MDM2 TT and p53 Pro/Pro genotypes (OR = 1.09, 95% CI = 0.63-1.88).These results suggest that genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population.

This study was aimed to investigate the association between mthfr gene polymorphisms and toxicity of HDMTX in acute lymphocytic leukemia patients. A total of 44 patients were selected, and DNA was extracted from their peripheral blood. PCR-RFLP was used to determine the genotypes of mthfr. The toxicity response of patients received HDMTX chemotherapy was observed. The results showed that the toxicity of HDMTX to carriers of the variant allele at codon 677 (CT or TT) increased, as compared with individuals with the common CC genotype (OR = 3.75, 95% CI 1 - 14, p = 0.04). In contrast, the toxicity of HDMTX to ALL patients with the variant allele at codon 1298 (AC or CC) decreased as compared with the common AA genotype carriers (OR = 0.12, 95% CI: 0.026 - 0.564, p = 0.007). As compared with carriers of the variant allele at coden 1298 (AC or CC), the toxicity of HDMTX to patients with TT genotype at 677 and AA genotype at 1298 increased (OR = 16.5, 95% CI: 0.026 - 0.564). It is concluded that mthfr gene polymorphisms associate with the toxicity of HDMTX chemotherapy in acute lymphocytic leukemia.

To study the association between polymorphism of DNA repair gene XRCC3 Thr 241 Met and the risks of developing laryngeal and hypopharyngeal carcinomas.One hundred and seventy five patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model.The XRCC3 241 Met allele increased the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. Comparing with subjects having the XRCC3 241 Thr/Thr genotype, the subjects at least having one XRCC3 241 Met allele had OR of 2. 26 (95% CI 1.33 -3.82). Respectively analyzing the risks of laryngeal carcinoma and hypopharyngeal carcinoma, The allele XRCC3 241 Met increased the risks of developing both laryngeal and hypopharyngeal carcinoma. Comparing with the subjects having the XRCC3 241 Thr/Thr genotype, the subjects with laryngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2.27 (95% CI 1.26 - 4.09); the subjects with hypopharyngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2. 99 (95% CI 1.27 - 7.04). Smoking may increase the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. The interaction of smoking and XRCC3 Thr241 Met increased risk of laryngeal carcinoma and hypopharyngeal carcinoma in a super-multiplicative manner. The subjects with heavy smoking and at least having one XRCC3 241Met allele had OR of 19.09 (95% CI 7.38 -49.40) comparing with those having the XRCC3 241 Thr/ Thr genotype and no smoking, which was greater than the multiplication of ORs both of subjects at least having one 241 Met allele meanwhile without smoking (OR, 0.91; 95% CI, 0.20 - 4.21) and of subjects having XRCC3 241 Thr/Thr genotype meanwhile with smoking (OR, 4.13; 95% CI, 2.38 - 7.17).XRCC3 Thr 241 Met plays an important role in the development of laryngeal and hypopharyngeal carcinoma.

To study the association between polymorphism of DNA repair gene xeroderma pigmentosum G (XPG) Asp1104His and the risks of developing laryngeal and hypopharyngeal carcinomas.Totally 175 patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model.Compared with those having the Asp/Asp genotype, patients having the XPG 1104Asp/His genotype had a higher risk for laryngeal carcinoma (OR = 2.46, 95% CI = 1.15-5.24, P0.05), but not for hypopharyngeal carcinoma (OR = 1.36, 95% CI = 0.87-2.12, P0.05). In addition, the XPG 1104Asp/His genotype appeared to be associated with well differentiated squamous cell carcinoma in both larynx and hypopharynx (OR = 1.88, 95% CI = 1.05-3.40, P0.05 ).The XPG Asp1104His polymorphism may play a role in the development of laryngeal and hypopharyngeal carcinomas.

DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.

It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro--Arg and p73 exon 2 G4C14--A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the 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. All statistical tests were two-sided.The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.

This case-control study was designed to detect the association between STK15 Phe31Ile polymorphism and colorectal cancer.Genotypes were determined in 283 patients with colorectal cancer and 283 controls. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression model.The frequency of the STK15 Ile/Ile genotype was significantly higher in cancer cases than in controls (50.2% vs. 36.8%; P = 0.02). Subjects with the Ile/Ile genotype had an increased risk for the occurrence of colorectal cancer compared with those with the STK15 Phe/Phe genotype (adjusted OR, 1.92; 95% CI, 1.13 - 3.27). No significant association was observed between this STK15 polymorphism and risk of metastasis of the cancer.These findings suggest that STK15 Phe/Ile polymorphism may be a genetic susceptibility factor for colorectal cancer among Chinese.

To determine whether genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer.A hospital-based, case-control study consisting of 101 incident pancreatic cancer cases and 337 controls matched on age, sex and race was conducted to investigate the association between polymorphism in MTHFR and MS, and susceptibility to pancreatic cancer. Genotypes of MTHFR C677T, A1298C and MS A2756G were analyzed by polymerase chain reasction-restriction fragment length polymorphism methods.It was found that multivariate-adjusted odds ratio (ORs; 95% confidence interval) for MTHFR-677CT and 677TT compared with 677CC were 2.17 (1.26 - 3.85) and 3.53 (1.85 - 6.84) respectively, which was in a manner of allele-dose relationship. However, no significant association between the A1298C genotype alone and the risk of cancer was observed which seemed that this polymorphism had a combined effect with the C677T polymorphism. A significant gene-environment interaction was observed between C677T polymorphism and cigarette smoking or alcohol intake. Subjects with variant genotypes who smoked17 pack-years had highest risk for developing the cancer, with the OR of 5.58 (2.53 - 12.30). Similarly, the OR (3.27, 1.51 - 7.23) for subjects with variant genotypes of alcohol drinker was significantly higher than that for subjects either having the variant genotype or being drinkers. No association was found between MS A2756G polymorphism and risk of pancreatic cancer in the study.These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.

To examine the genetic polymorphisms in the promoter region of cyclooxygenase-2 ( COX-2) and evaluate their association with the risk of gastric cancer.Single-strand conformational polymorphism and DNA sequencing were used to screen the genetic variants of the COX-2 promoter region. Total 323 patients with gastric cancer and 646 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Haplotype frequency was estimated using Haplo. stat software.Three single nucleotide polymorphisms, including - 1290AG, -1195GA, and -765GC were identified in the promoter of COX- 2. Case-control analysis showed an increased risk of developing gastric cancer for the -1290AG (OR 1.64; 95% CI 1.03-2.61), -1195AA (OR 2.68; 95% CI 1.65-4.33), and -765CG (OR 2.66; 95% CI 1.53-4.64) genotype carriers, respectively, compared with noncarriers. A greater risk of developing gastric cancer was observed for the A(-1290) -A(-1195) -C(-765) haplotype compared with the A(-1290) -G(-1195) -G(-765) haplotypes (OR 11.80; 95% CI 2.43-57.25).Genetic polymorphisms in COX-2 promoter region may play a role in gastric carcinogenesis.

To investigate the association between methylentetrahydrofolate reductase (MTHFR) polymorphisms and risk of lung cancer.Totally 505 cases with lung cancer and 500 frequency-matched controls were genotyped for the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methods. The odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression model. Haplotype frequency was estimated using EH software.The frequency of the MTHFR C677T allele in cases was significantly higher than that in controls (53.5% vs 44.9%, P0.001). Compared with the 677CC genotype, the 677CT and 677TT genotypes were associated with increased risk of lung cancer, with the OR being 1.43 (95% CI, 1.04-1.95) and 2.40 (95% CI, 1.61-3.59), respectively. In addition, a significant difference in the distribution of haplotype frequencies between cases and controls was observed.Functional polymorphism in MTHFR is associated with increased risk of lung cancer in Chinese population.

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are 2 major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT 762Val--Ala and XRCC1 399Arg--Gln have been verified to associate with altered protein function and BER activity. This study was to examine the contribution of these 2 polymorphisms, alone or in combination, to the risk of developing gastric cancer.A total of 236 patients with gastric cancer and 708 cancer-free controls were genotyped for the 2 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the impact of these 2 polymorphisms on the risk of developing gastric cancer.The subjects having the ADPRT Ala/Ala genotype had an OR of 2.07 (95% CI=1.33-3.21; P=0.001) compared with those having the Val/Val genotype. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the risk of gastric cancer in a super-multiplicative manner, with an OR of 5.32 (95% CI=1.12-28.57) for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, although the XRCC1 polymorphism itself was not associated with the risk of gastric cancer.The ADPRT 762Val--Ala polymorphism plays an important role in the development of gastric cancer, and the XRCC1 399Arg--Gln polymorphism may serve as a risk modifier.

DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. This study was to examine the correlations of polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer (NSCLC) to platinum-based chemotherapy.Treatment outcomes of 200 advanced NSCLC patients, treated with platinum-based chemotherapy, were evaluated. XPC-PAT, XPD Lys751Gln (rs1052559), and ERCC1 C8092A (rs1052559) were genotyped by polymerase chain reaction-amplified fragment length polymorphism (PCR-AFLP) or PCR-restrictive fragment length polymorphism (PCR-RFLP) methods in the 200 patients. Unconditional logistic regression model was used to analyze the correlation of genetic polymorphisms to clinical response.The distributions of XPC-PAT genotypes differed significantly between response group (complete response + partial response) and un-response group (stable disease + progressive disease)(P=0.023). The XPC LL genotype carriers had higher response rate than the SS genotype carriers (OR=3.04; 95% CI=1.25-7.41, P= 0.015). The XPD Lys751Gln and ERCC1 C8092A polymorphisms were not found to be associated with platinum-based chemotherapy. However, these 3 genetic polymorphisms in nucleotide excision repair system had interaction in the drug sensitivity (P=0.021).The genetic polymorphisms of XPC-PAT, XPD Lys751Gln, and ERCC1 C8092A in nucleotide excision repair system may be associated with sensitivity of NSCLC patients to platinum-based chemotherapy.

To investigate the association between genetic variations in methylenetetrahydrofolate reductase (MTHFR) and the risk of colorectal cancer in a Chinese population.One hundred and ninety-eight cases of colorectal cancer and 420 controls were genotyped for detecting MTHFR C677T and A1298C polymorphisms by PCR-RFLP methods. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model.The frequency of the MTHFR C677T allele found among cases was significantly more frequent than that among controls (51.3% to 44.4%, P = 0.02). As compared with the 677CC genotype, the 677TT genotypes had a 67% (95% CI, 1.05 - 2.66) increased risk of colorectal cancers. However, there appeared no any correlations between the genetic variations of MTHFR and the cancer metastasis.These findings demonstrated that the genetic variation of MTHFR C677T should be a genetic susceptibility factor for colorectal cancer in a Chinese population.

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.

UDP-glucuronosyltransferase 1A7 (UGT1A7) plays an important role in detoxification through catalyzing combination of glucuronic acid and tobacco carcinogens, including benzo [alpha] pyrene, nitrosamine, and heterocyclic amine PhIP, therefore, inactivates the carcinogens. This study was to examine the correlation of polymorphisms of UGT1A7 gene to genetic susceptibility of lung cancer.Polymorphisms of UGT1A7 gene at 12-131 and 208 sites in peripheral lymph cells of 312 patients and 317 age- and sex-matched controls were detected by polymerase chain reaction-denaturized high performance liquid chromatography (PCR-DHPLC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); the correlation of these polymorphisms to genetic susceptibility of lung cancer was analyzed.Compared with the UGT1A7*1/*1 genotype carriers, the UGT1A7*3/*1 genotype carriers had a 1.80-fold increased risk of lung adenocarcinoma [adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.03-3.12], the UGT1A7*3 genotype carriers had a 1.59-fold increased risk of lung adenocarcinoma (adjusted OR, 1.59; 95% CI, 0.96-2.63). The UGT1A7 polymorphisms had no correlation with risk of lung squamous cell carcinoma.UGT1A7 gene polymorphisms may increase the genetic susceptibility of lung adenocarcinoma in Chinese.

To explore the relationship between two exonic polymorphisms of DNA repair gene XPC and the susceptibility to lung cancer.Genotypes were determined by the primer introduced restriction analysis-PCR(PIRA-PCR) and the PCR-restriction fragment length polymorphism(PCR-RFLP) approaches, respectively, in 320 histologically-confirmed lung cancer cases and 322 age and sex frequency-matched cancer-free controls.Multivariate logistic regression analysis revealed that individuals carrying at least one 499Val variant allele (Ala/Val + Val/Val genotypes) had a significantly increased risk for lung cancer (adjusted OR=1.54; 95%CI: 1.11-2.14), compared with the wild-type genotype (499Ala/Ala). Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR=2.55; 95%CI: 1.45-4.52), compared with those with both wild-genotypes. In addition, a potential super multiplicative gene-environment interaction between Ala499Val genotypes and smoking on lung cancer risk was unveiled. The odds ratios of lung cancer for individuals with both putative risk genotypes were 2.63 (95%CI=1.23-5.62) in nonsmokers and 7.36 (95%CI=3.19-17.0) in smokers, respectively.These findings support the hypothesis that these two XPC variants may contribute to the risk of developing lung cancer.

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.

To study the relationship between two potential functional polymorphisms in exon 2 of the p73 gene and the susceptibility of lung cancer.Genotypes were determined by polymerase chain reaction-single stand conformation polymorphism (PCR-SSCP) method in 425 histologically-confirmed lung cancer cases and 588 cancer-free controls, frequency-matched by age and sex.The two polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less commonly seen in the cases (0.225) than in the controls (0.287) (P = 0.0018). Compared with the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk [adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26 - 0.80 and OR = 0.70, 95% CI = 0.53-0.92, respectively].These results suggested that this p73 dinucleotide polymorphism might have had a role to play in the susceptibility of lung cancer.

Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play important roles in the development of gastric cancer. This study was to investigate the association of functional polymorphisms in the MMP-2 and MMP-9 genes with risk of gastric cancer in a Chinese population.MMP-2 -1306T/C,and MMP-9 -1562C/T polymorphisms in 228 patients with gastric cancer, and 774 matched healthy controls were detected by polymerase chain reaction (PCR)-based denaturing high performance liquid chromatography, and PCR-based restriction fragment length polymorphism analysis. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. The effect-modified model was used to evaluate the gene-gene interaction.Subjects with the MMP-2 -1306CC genotype had an increased risk of developing gastric cancer compared with those with the MMP-2 -1306TT or CT genotype (adjusted OR, 1.67; 95% CI, 1.17-2.38). No significant association between MMP-9 -1562C/T polymorphism and risk of gastric cancer was observed. However, the polymorphisms in these 2 genes seem to display a gene-gene interaction, with OR of 1.72 (95% CI, 1.07-2.78) for subjects carrying both MMP-2 -1306CC and MMP-9 -1562TT or CT genotypes compared with those carrying both MMP-2 -1306TT or CT and MMP-2 -1306T/C genotypes (likelihood ratio test, P=0.02).MMP-2 -1306T/C and MMP-9 -1562C/T polymorphisms may be associated with genetic susceptibility to gastric cancer.

To investigate the association between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and risk of breast cancer among women.Two hundred seventeen cases with breast cancer and 218 matched controls were genotyped for the MTHFR C677T and A1298C polymorphisms by PCR-RFLP methods. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model.We found that the frequency of the MTHFR C677TT genotype among cases was significantly different from that among controls (32.7% vs. 24.8%; P = 0.02). The MTHFR C677TT genotype had an increased risk of breast cancer compared with the 677CC genotype (95% CI, 1.09 - 3.14). No significant association between the MTHFR C677T or A1298C polymorphism and risk of the cancer was observed.These findings suggest that 677CT polymorphism in MTHFR may be a genetic susceptibility factor for breast cancer among Chinese women.

DNA repair capacity correlated with sensitivity of cancer cells towards platin-based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin- or carboplatin-based chemotherapy of advanced non-small cell lung cancer (NSCLC).Totally 105 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression.The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1% vs. 20.3%;OR=2.97,95% CI=1.15-7.72;P0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5% vs. 21.2%;OR=2.65,95% CI=1.03-6.87;P0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7% which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0% to 23.1%, P0.001).Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin-based chemotherapy.

It has been shown that suboptimal DNA repair capacity is associated with cancer risk and that a poly(AT) polymorphism in XPC gene (XPC PAT) may influence DNA capacity. This study was designed to assess the relationship between XPC PAT polymorphism and susceptibility to lung cancer in the Chinese population.XPC genotypes were determined by PCR methods in 509 healthy controls and 597 patients with lung cancer. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression model.Genotype frequencies of XPC PAT among controls were 37.9% (PAT-/-), 49.7% (PAT+/-) and 12.4% (PAT+/+), respectively. They were not significantly different from those among lung cancer patients (42.1%, 46.7% and 11.2%, respectively; P = 0.37). Individuals carrying XPC PAT+/+ genotype were not at increased risk for lung cancer as compared with those with PAT+/- or PAT-/- genotype (adjusted OR, 0.8; 95% CI, 0.55 approximately 1.16). No interaction between XPC genotype and smoking was observed.Our findings indicate that the XPC PAT polymorphism may not be associated with risk of lung cancer in the Chinese population.

To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women.COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR-based restriction fragment length polymorphism analysis in 250 breast cancer patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression.COMT Met/Met genotype was found in 10.4% of breast cancer patients, which was significantly higher (P = 0.03) than that in controls (5.2%). Women with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR 2.1, 95% CI 1.1 - 4.5) compared with those with Val/Val or Val/Met genotypes. Stratified analysis showed that the elevated risk of breast cancer, associating with the COMT Met/Met genotype, was evident only among premenopausal women (adjusted OR 4.1, 95% CI 1.2 - 17.3) but not among postmenopausal women (adjusted OR 1.3, 95% CI 0.5 - 3.5). There was no significant difference in the distribution of CYP17 genotypes between breast cancer patients and the control subjects (P = 0.83).The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.

Folate is one of the important constituents of vegetables and fruits that may provide protection against cancer. An important function of folate is to provide methyl groups required for intracellular methylation reactions and de novo deoxynucleoside synthesis. Therefore, folate deficiency has been thought to be carcinogenic through disruption of DNA methylation, synthesis, and repair. However, to serve as the active mediator, folate requires metabolism catalyzed by several enzymes including methylenetetrahydrofolate reductase (MTHFR), which plays a central role in biotransformation of folate. Thus, it is likely that two functional single nucleotide polymorphisms(677C--T and 1298A--C) in the MTHFR gene,both of which diminishes MTHFR activity,may contribute to risk of cancer.

XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study.Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression.Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0.55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smokingor=29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found.The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.

Background/Aim: Cyclooxygenase-2 (COX-2) is one of the key isoenzymes in the production of prostaglandins, and is believed to be involved in carcinogenesis. This study was conducted to examine the role of COX-2 in the development and biological behavior of stomach cancer. Methods: Expression of COX-2 at the mRNA and protein levels was analyzed using RT-PCR and immunoblotting assay in 50 cancerous and corresponding non-cancerous tissue specimens. Also, COX-2 expression was detected by an immunohistochemical method in 55 paraffin-embedded gastric adenocarcinoma tissues. Results: Of the 50 carcinoma tissue samples analyzed, 38 (76.0%) had overexpression of COX-2 as compared to the paired non-cancerous specimens. The overexpression of COX-2 (91.7%) was more prevalent in tumors with sizes of >5 cm than those (61.5%) of ≤5 cm (p < 0.05). COX-2 overexpression was higher in tumors with >6 metastatic nodes compared to those with ≤6 metastatic nodes (100.0 vs. 61.3%, p < 0.01). The rate of COX-2 overexpression in non-signet ring cell carcinoma was significantly higher compared with signet ring cell carcinoma (84.1 vs. 16.7%, p < 0.05). The rate of COX-2 overexpression (86.8 or 90.9%) in patients with a cancer invasion depth of pT3 + pT4 or with stage III + IV was significantly higher than that (41.7 or 47.1%) in patients with pT1 + pT2 or with stage I + II (both p < 0.01). Furthermore, consistent with the results at the protein and mRNA levels, immunohistochemical stain indicated that COX-2 protein was overexpressed in 39 of 55 (70.9%) carcinomas, and the 5-year survival rate (25.6%) for patients with COX-2 overexpression seemed better than that (50.0%) of patients without overexpression, though the difference was not significant (p < 0.05). Conclusion: Our results indicate that COX-2 may play a role in the development of gastric cancer and its overexpression is associated with lymphatic metastasis, tumor invasion and differentiation of gastric carcinoma.

AIM:The food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo 4,5-b pyridine (PhIP) induces colon and mammary gland tumors in rats and has been implicated in the etiology of human colorectal cancer.This study was conducted to examine the potentially preventive effect of Chinese cabbage (Brassica chinensis),a brassica vegetable most commonly consumed in China, against this carcinogen-induced DNA adduct formation in rats and its possible mechanisms.METHODS:Sprague-Dawley rats were maintained for 10 days on basal diet or diet containing 20% (w/w) freeze-dried cabbage powder prior to administration of a single dose of PhIP (10mg/kg) by oral gavage. Rats were sacrificed at 20h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung and liver were analyzed using (32)P-postlabeling technique. Levels of hepatic cytochrome P450 (CYP)1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7-methoxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases (GSTs) towards 1-chloro-2, 4-dinitrobenzene (CDNB) in the liver, lung and colon were measured.RESULTS:Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced levels of PhIP-DNA adducts in the colon, heart, lung and liver, with inhibition rates of 82.3%, 60.6%, 48.4% and 48.9%, respectively (P0.01). The enzyme assays revealed that Chinese cabbage induced both CYP1A1 and 1A2 activity, but the induction was preferential for CYP1A1 over 1A2 (81% vs 51%).GST activity towards CDNB in the liver and lung, but not colon, was also significantly increased by cabbage treatment.CONCLUSION:The results indicate that Chinese cabbage has a preventive effect on PhIP-initiated carcinogenesis in rats and the mechanism is likely to involve the induction of detoxification enzymes.