Codon 201Arg/Gly Polymorphism of DCC (Deleted in Colorectal Carcinoma) Gene in Flat- and Polypoid-Type Colorectal Tumors

Recent studies have identified the distinctexistence of flat-type colorectal tumors. The lowincidence of ras gene mutations in these tumors suggeststhat their genetic pathways of tumor progression may be different from those of the polypoid type.To elucidate further genetic alterations in flat-typecolorectal tumors, codon 201^Arg/Glypolymorphism in the DCC (deleted in colorectalcarcinoma) gene was analyzed in normal tissue (normal colonicmucosa or peripheral lymphocytes) and in tumor tissuefrom 191 patients with colorectal tumors (36 patientswith flat-type colorectal tumors, 81 patients withpolypoid-type colorectal tumors, and 74 patients withadvanced carcinomas). For normal controls, 30 samplesobtained from patients who had neither colorectal tumors(confirmed by total colonoscopy) nor a family history of colorectal carcinoma were analyzed. DCC genecodon 201^Arg/Gly polymorphism wasinvestigated by polymerase chain reaction-basedrestriction fragment length polymorphism analysis,fluorescence-based dideoxy sequencing, or both. For the flat type, thefrequency of codon 201^Gly of the DCC gene was64% and 54% in the normal tissue of patients withadenoma with high-grade dysplasia and submucosalcarcinoma, respectively. It was 49%, 52%, and 49% in the normal tissueof patients with polypoid-type adenoma with high-gradedysplasia, submucosal carcinoma, and advanced carcinoma,respectively. In the normal tissue, codon 201Gly of the DCC gene was more frequentlyobserved in patients with flat-type adenoma withlow-grade dysplasia (67%) than in those withpolypoid-type adenoma with low-grade dysplasia (18%) orin normal controls (17%, P < 0.05, ²test). Codon 201^Arg/Gly polymorphism in tumortissues did not differ from that in the correspondingnormal tissues, except for 10 cases of carcinoma withloss of heterozygosity (LOH). In carcinomas with LOH, preferentialloss of the codon 201^Arg allele was noted(9/10 cases). These results suggest that codon201^Gly of the DCC gene is not only associatedwith flat-type colorectal tumors, but that it may serve as a usefulgenetic marker for identifying groups at higher risk forcolorectal cancer.     

TP53 Codon 72 Polymorphism and the Risk of Colorectal Cancer in an Azerbaijani Population

Background:We aimed to evaluate the association between the TP53 Arg72Pro gene polymorphism and risk of colorectal cancer in an Azerbaijani population.Methods: A total of 141 patients with colorectal cancer and 150 gender- and age-matched controls were involved in the study. The genotypes of the TP53 gene Arg72Pro polymorphism were detected by polymerase chain reaction-based restriction fragment length polymorphism analysis.Results: We found that the heterozygous genotypes Arg/Pro (odds ratio, 1.128; 95% CI, 0.657-1.937) and mutant Pro/Pro (odds ratio, 1.274; 95% CI, 0.648-2.504) were more frequent in colorectal cancer patients compared to healthy controls. The frequency of the mutant Pro allele (odds ratio, 1.122; 95% CI, 0.809-1.554) was revealed in 47.5% of colorectal cancer patients and in 44.7% of healthy controls. There was no association observed between TP53 Arg72Pro polymorphism and risk of colorectal cancer in an Azerbaijani population (P > .05).Conclusion: Our findings indicate a lack of relationship between TP53 Arg72Pro polymorphism and risk of colorectal cancer. Furthermore, we have found no statistical differences in the frequency of genotype and allele by sex, age, histological grade, tumor stage, smoking status, and alcohol consumption in this study.     

Variant Toll-like receptor4 (Asp299Gly and Thr399Ile alleles) and Toll-like receptor2 (Arg753Gln and Arg677Trp alleles) in colorectal cancer

The innate immune system recognizes the presence of bacterial products through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Polymorphisms in TLRs have been shown to be associated with increased susceptibility to diseases such as inflammatory bowel disease. The aim of this study was to determine whether there was a correlation between polymorphisms of TLR4 (Asp299Gly; Thr399Ile) and TLR2 (Arg677Trp; Arg753Gln) genes and risk of colorectal cancer. DNA from 60 colorectal carcinoma patients from 3 major races in Malaysia (22 Malays, 20 Chinese and 18 Indians) and blood from 50 apparently healthy individuals were evaluated. Control group were matched to study group by race and age. The polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Genotyping results showed two out of sixty tumour specimens (3.3%) harbored both variant TLR4 Asp299Gly and Thr399Ile alleles. In contrast, DNA isolated from blood cells of 50 apparently healthy individuals harbored wild type TLR4. In the case of TLR2 Arg753Gln genotyping, all of the fifty normal and 60 tumours were of the wild type genotype. TLR2 Arg677Trp genotyping showed a heterozygous pattern in all samples. However, this may not be a true polymorphism of the TLR2 gene as it is likely due to a variation of a duplicated ( pseudogene) region. There was only a low incidence (2/60; 3.3%) of TLR4 polymorphism at the Asp299Gly and Thr399Ile alleles in colorectal cancer patients. All normal and tumour samples harbored the wild type TLR2 Arg753 allele. Our study suggests that variant TLR4 (Asp299Gly and Thr399Ile alleles) as well as TLR2 (Arg753Gln allele) are not associated with risk of colorectal cancer.     

Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients

AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P =     

CD14及Toll样受体4基因多态性与大肠癌的相关性研究

目的探讨我国湖北汉族人Toll样受体（TLR）4基因Asp299Gly和CD14 C-260T基因多态性分布与大肠癌的相关性。方法采用聚合酶链反应限制性片段长度多态性（PCR—RFLP）方法，检测110例大肠癌患者及160例正常对照者TLR4基因Asp299Gly及CD14 C-260T基因型及等位基因频率的分布。结果大肠癌组CD14 C-260T基因型与正常对照组比较，差异有统计学意义（P〈0．05）。正常对照组CC基因型的频率为15．6%，明显低于大肠癌组的31．8％（P=0．0027，OR=0．3968，95％CI=0．2209～0．7129）；正常对照组中CT基因型的频率为48．1％，明显高于大肠癌组的30．9％（P=0．0056，OR=2．074，95%CI=1．246～3．452）。所有样本中均未发现TLR4基因Asp299Gly的突变型。结论CD14 C-260T基因多态性与中国湖北汉族大肠癌显著相关，而TLR4基因Asp299Gly多态性与大肠癌无关。     

Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in The Netherlands

PURPOSE: Identification of the hereditary non-polyposis colorectal carcinoma syndrome (HNPCC) is a basis for secondary prevention. The objectives of this study are to investigate the natural history of HNPCC and to assess the effect of screening. PATIENTS AND METHODS: Screening for colorectal carcinoma was performed in 22 HNPCC families (colonoscopy or double-contrast barium enema and sigmoidoscopy). The patients were subdivided into two groups. Group A comprised patients with colorectal cancer who were referred because they were symptomatic. Group B included family members of these patients who were found to have a colorectal lesion by screening. We compared these groups with respect to the stage of tumor growth. RESULTS: Histologic examination of the tumors in Group A (87 patients) revealed Dukes A carcinomas in six patients, Dukes B carcinomas in 37, Dukes C carcinomas in 21, and Dukes D carcinomas in 10 patients (classification unknown in 13 patients). In Group B (20 patients), adenoma was found in 14 and carcinoma in six patients (Dukes A in two and Dukes B in four patients). A total of 93 patients, including those whose tumors were detected by screening, had a colorectal carcinoma. The age at diagnosis ranged from 24 to 81 years (mean age: 46 years). The location of the colonic tumors was proximal in 60 percent. Multiple primary tumors were found in 26 percent. CONCLUSION: These results suggest that screening leads to the early detection of colorectal carcinomas and adenomas in asymptomatic members of HNPCC families. Screening should be initiated at the age of 20 and continued during the life of the individual. Careful examination of the right colon is indicated because of the frequent occurrence of tumors in the proximal colon. A subtotal colectomy is indicated at the time of diagnosis of the initial colon cancer because of the risk of multiple primary tumors.     

Polymorphism of CD14 gene but not the mutation of TLR4 gene is associated with colorectal cancer in Chinese patients

Objectives: Toll‐like receptor 4 and CD14 are components of the lipopolysaccharide receptor complex. Our study aimed to investigate an association between TLR4 Asp299Gly and CD14‐260 polymorphisms in Chinese patients with colorectal cancer. Method: By a method of polymerase chain reaction–based restriction fragment length polymorphism (PCR‐RFLP), we genotyped TLR4 Asp299Gly and CD14‐260 polymorphisms in 110 unrelated patients with colorectal cancer and 160 healthy controls from the Chinese Han population. Results: We found significant differences in CD14 genotypes between healthy controls and patients with colorectal cancer. The frequency of the C/C genotype in healthy controls (15.6%) was significantly lower than in the group of colorectal cancer patients (32%). The frequency of the C/T genotype in healthy controls (48.1%) was significantly higher than that in the group of colorectal cancer patients (31%). No TLR4 Asp299Gly mutation was detected in any patients or healthy controls in the Chinese Han population. Conclusions: These findings indicated that the polymorphism of CD14 but not TLR4 Asp299Gly mutation was associated with Chinese patients with colorectal cancer, and the CD14 gene may contribute to the predisposition to colorectal cancer. Screening for the CD14 C‐260T genotype is likely to be a useful tool for risk assessment or prognostication for colorectal cancer in the Chinese Han population.     

转化生长因子β1-509C／T基因多态性与大肠癌的关系

目的研究转化生长因子β1（TGF—β1）基因-509位点C／T的多态性,并探讨其与大肠癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,检测70例大肠癌组和102例对照组TGF—β1基因-509位点C／T等位基因及基因型分布,并对该基因多态性与大肠癌临床病理特征之间的关系进行分析。同时采用酶联免疫吸附试验（ELISA）检测大肠癌组和对照组血清TGF—β1水平。结果TGF—β1等位基因频率及基因型频率在大肠癌组和对照组的总体分布比较无显著性差异。大肠癌组按Dukes分期后,发现DukesC＋D期大肠癌患者-509CT／TT基因型频率明显高于DukesA＋B期患者（64．9％比39．4％,P=0．033,OR=2．840,95％CI：1．075～7．501）。DukesC＋D期大肠癌患者与DukesA＋B期相比,-509T等位基因频率有增高趋势（41．9％比27．3％,P=0．07,OR=1．922,95％CI：0．943～3．917）,但差异无显著性。大肠癌患者血清TGF—β1水平显著高于对照组。结论TGF—β1-509位点基因多态性与大肠癌无关,可能与大肠癌临床分期有关。     

TLR4基因Asp299Gly及TLR2基因Arg753Glu、Arg677Trp多态性与中国湖北汉族炎症性肠病无相关性

目的:研究TLR4基因Asp299Gly及LTLR2基因 Arg753Glu及Arg677Trp多态性在中国汉族人群中的分布,探讨其与炎症性肠病的相关性．方法:采用聚合酶链反应-限制性片段长度多态性方法,检测120例中国湖北汉族炎症性肠病患者与110例正常对照者TLR4 基因ASp299Gly及TLR2基因Arg753Glu及 Arg677Trp基因型,分析该基因多态性与炎症性肠病以及临床亚型的相关性．结果:炎症性肠病患者和健康对照者均未检测出TLR4基因ASp299Gly及TLR2基因 Arg753Glu及Arg677Trp突变型．结论:TLR4基因Asp299Gly及TLR2基因 Arg753Glu及Arg677Trp基因多态性与中国湖北汉族人群炎症性肠病的易感性无相关性．     

The Human Leukocyte Antigen Region and Colorectal Cancer Risk

PURPOSE Recently, we found a certain haplotype in the human leukocyte antigen Class III subregion to be associated with breast cancer. Epidemiologic studies have shown that breast cancer and colorectal cancer have several risk factors in common. In view of these studies and because polymorphisms located in the human leukocyte antigen III region have been found to be associated with colorectal cancer, we wondered whether the same region also is involved in colorectal cancer susceptibility.METHODS The human leukocyte antigen region was genotyped with 14 microsatellite markers in germline DNA from 643 colorectal cancer patients and 841 family-based controls. Association analyses and the Haplotype Sharing Statistic were used to search for differences between patients and controls. Subgroup analyses were performed for gender, age at diagnosis, and localization of the tumor.RESULTS The Haplotype Sharing Statistic analysis revealed neither a difference in mean haplotype sharing between all patients and controls, nor in any of the subgroups. The single allele, genotype, and two-locus association analyses for all patients and for the different subgroups did not show an association with colorectal cancer for the 14 microsatellite markers. Also, no association was observed between the tumor necrosis factor-beta polymorphism and colorectal cancer.CONCLUSIONS No association was observed between commonly occurring haplotypes and alleles in the human leukocyte antigen region and colorectal cancer risk.© The American Society of Colon and Rectal SurgeonsPublished online: 28 January 2005.     

β2肾上腺素能受体基因多态性与岳西地区高血压患者血压的关系

目的探讨岳西地区人群β2肾上腺素能受体（ADRB2）基因Arg16Gly多态性与血压相关性。方法用RFLP方法对安徽省岳西地区487例高血压病患者及672例家属的B：。肾上腺素能受体基因的Arg16／Gly多态性位点进行了检测,应用了以家系为基础的分析方法,分析了岳西地区成年高血压人群ADRB2多态位点与高血压的相关性。结果在岳西人群中,带有ADRB2 Arg16等位基因的高血压病患者的收缩压（P=0．003）和舒张压（P=0．003）水平都较低,遗传对血压的影响更适合于共显性模型。结论ADRB2基因Gly16等位基因与高血压可能存在相关关系。     

No evidence of increased risk of colorectal cancer in individuals heterozygous for the Cys282Tyr haemochromatosis mutation

BACKGROUND AND AIMS: Previous studies have suggested that increased body iron stores and heterozygosity for haemochromatosis are associated with an increased risk of colorectal carcinoma. The aim of this study is to determine if there is an association between (i) colorectal carcinoma and heterozygosity for the Cys282Tyr mutation of the haemochromatosis gene (HFE) and (ii) this mutation and tumour site or stage. METHODS: Two hundred and twenty-nine unselected patients (127 males, 102 females, mean age 68.0 years) with sporadic colorectal carcinoma and 228 controls (145 males, 83 females, mean age 69.7 years) were studied. DNA was tested for the presence of the Cys282Tyr mutation by digestion with Rsa1 and fragments separated by electrophoresis. RESULTS: Twenty-one patients with colorectal cancer and 23 control subjects were heterozygous for the Cys282Tyr mutation of HFE (relative risk 0.90). There was no association between heterozygosity of the Cys282Tyr mutation and tumour site or stage. CONCLUSIONS: Heterozygosity for the Cys282Tyr mutation of HFE does not appear to be a risk factor for colorectal carcinoma.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study

Type 2 diabetes mellitus (T2D) is a main public health problem in the Mexican population. It is characterized by insulin resistance in peripheral tissues and a relative deficiency in the pancreatic β-cell functions. Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D risk. The aim of this study was to identify the association between known IRS1 polymorphisms (Pro512Ala, Asn1137Asp, Gly972Arg, and Arg158Pro) in a sample of diabetic patients compared with healthy controls selected from Mexico's 2000 National Health Survey, both with normal body mass index (BMI). We identified 444 diabetes cases that were age matched with the same number of controls. Genotypic and allelic frequencies were evaluated, and conditional logistic regression was used to evaluate the association between the SNPs and diabetes risk. Of the 4 SNPs studied, only Gly972Arg showed significant differences between cases and controls, with allele frequency of 2.6% in controls as compared with 7.9% in cases. Subjects with at least 1 copy of the Gly972Arg polymorphism of the IRS1 gene showed a greater risk for diabetes, with a crude odds ratio of 3.26 (95% confidence interval, 2.00-5.33); after adjusting for BMI, age, family history of T2D, and sex, the odds ratio was 2.91 (95% confidence interval, 1.73-4.90). Our results suggest the participation of Gly972Arg polymorphism of IRS1 in the genetic susceptibility to TD2 in Mexican population. The restriction of including only participants with normal BMI might increase the power to detect genetic determinants of T2D.     

Association of NOD2/CARD15 mutations on Crohn's disease phenotype in an Italian population

AIMS: To confirm the prevalence of NOD2/CARD15 mutations in Italian inflammatory bowel disease patients and to define the role of the different mutations on Crohn's disease phenotype. PATIENTS AND METHODS: A total of 177 patients with Crohn's disease and 92 patients with ulcerative colitis and 164 control participants were investigated for the presence of Arg702Trp, Gly908Arg and Leu1007fsinsC NOD2/CARD15 mutations. Allele frequencies in Crohn's disease and ulcerative colitis patients were compared with those observed in the control population. Genotype-phenotype correlations with the major clinical features were also established and estimated risks (odds ratio with 95% confidence interval) for the mutations were calculated by logistic regression and multiple correspondent analysis. RESULTS: Gly908Arg and Leu1007fsinsC mutations were significantly more frequent in Crohn's disease patients compared with healthy controls (P<0.01 and <0.003 respectively). Indeed, using a logistic regression model adding terms for age (differently distributed between cases and controls) and sex, a significantly increased risk of having Crohn's disease compared with healthy controls was found for all NOD2 mutations: Leu1007fsinsC (odds ratio=7.35; 95% confidence interval: 1.73-31.3), Gly908Arg (odds ratio=5.70; 95% confidence interval: 1.37-23.7) and Arg702Trp (odds ratio=2.45; 95% confidence interval: 1.10-5.47). As far as the genotype-phenotype correlations are concerned, by multivariate conditional logistic regression methods, we found a significant association between Gly908Arg mutations and familial history of inflammatory bowel disease, between Leu1007fsinsC mutations and appendectomy and between Arg702Trp mutations and fibrostenotic phenotype of Crohn's disease. A nonsignificant association between Arg702Trp variants and ileal disease was also found (odds ratio=8, 95% confidence interval: 0.99-64.9). CONCLUSIONS: The results of the study confirm a significant association of CARD15 gene mutations in our Italian Crohn's disease population and the impact of different NOD2/CARD15 mutations on specific disease phenotypes.     

Depressed-type （0-IIc） colorectal neoplasm in patients with family history of first-degree relatives with colorectal cancer： A cross-sectional study

AIM: To investigate the correlation of depressed-type (0-IIc) colorectal neoplasm and family history of first-degree relatives (FDR) with colorectal cancer (CRC). METHODS: This cross-sectional study was conducted from June 2000 to October 2002 at National Cancer Center Hospital East. Eligible patients undergoing initial total colonoscopy were surveyed regarding family history of CRC among FDR by a questionnaire prior to colonoscopic examinations. All endoscopic findings during colonoscopy were recorded and the macroscopic classification of the early stage neoplasm/cancer was classified into two types (0-IIc vs non 0-IIc). Odds ratios (OR) and 95% confidence intervals (CI) were calculated by univariate and multivariate logistic regression to estimate the association between macroscopic features and clinicopathological data including gender, age, and family history of FDR with CRC. RESULTS: The OR of an association between family history of FDR with CRC and overall early stage neoplasm adjusted by gender and age was 1.85 (95% CI: 1.31-2.61, P = 0.0004), that for non 0-IIc neoplasm was 1.71 (95% CI: 1.22-2.41, P = 0.0017) and for 0-IIc colorectal neoplasm was 2.78 (95% CI: 1.49-5.16, P = 0.0031). CONCLUSION: Our study shows a significant association between a family history of FDR with CRC and 0-IIc colorectal neoplasm. When patients with a family history of FDR with CRC undergo colonoscopy, colonoscopists should check carefully for not only polypoid, but also depressed-type (0-IIc) lesions.     

p53 codon 72 polymorphism and susceptibility malignancy of colorectal cancer in Taiwan

Purpose The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. A recent report suggests that a polymorphism of the p53 tumor suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in the malignant transformation of colorectal adenoma to cancer.Methods In our study, the samples consisted of 150 patients were analyzed for the mutation in the p53 gene. The age of 150 patients (46 women and 104 men) ranged from 30 to 91 years (mean age 68.46 years).Results The polymorphism showed 52.04% mutant in the codon 72 of exon 4 in the Taiwanese population. Both of the chi-square for trend test (chi-square=4.97, p=0.034) and logistic regression (p=0.037, odds ratio=1.699) showed significant differences in the distribution of polymorphism of codon 72 in the p53 gene and Dukes classification of colorectal cancer.Conclusions There were significant relationship between the polymorphism of codon 72 and the malignancy of colorectal cancer in Taiwanese population. There is 1.70 times in each grade change (Dukes A–D) more risk of CCC polymorphism than that of CCG polymorphism of codon 72 of exon 4.     

The Arg16Gly polymorphism of human beta2-adrenoreceptor is associated with type 2 diabetes in Taiwanese people

OBJECTIVE: The significance of the association of amino terminal polymorphisms in beta2-adrenoreceptor (ADRB2) with obesity and type 2 diabetes is controversial and differs among ethnic groups. In this study, the association of ADRB2 with risk and age of onset of type 2 diabetes has been examined in a Taiwanese population. DESIGN: The study design is a case-control study to investigate the impact of the two amino acid polymorphisms in ADRB2. PATIENTS AND MEASUREMENTS: This study includes 130 patients with type 2 diabetes [female : male = 1 : 1, age: 52.4 +/- 10.0 years; body mass index (BMI): 24.2 +/- 2.9 kg/m2; mean +/- SD] and 130 controlled subjects matched for gender, age and BMI with normal glucose tolerance (female : male = 1 : 1, age: 51.7 +/- 10.6 years; BMI: 23.9 +/- 2.7 kg/m2). The Arg16Gly and Gln27Glu polymorphisms of ADRB2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. The genotypic and allelic frequencies between two groups were compared and the relationship between the genotypes and clinical phenotypes was examined. RESULTS: A difference in genotypic frequency in the Arg16Gly polymorphism was noted between groups in this gender-, age- and BMI-matched case-control study (P = 0.039). Multivariate regression analysis revealed that the Arg16Gly polymorphism was the only independent factor for development of type 2 diabetes (P = 0.021). In addition, we utilized the log-rank test to compare the differences in age of onset between wild-type and nonwild-type polymorphisms. The Arg16Gly polymorphism was independently associated with age of onset in type 2 diabetes (P = 0.017). There was no difference in the Gln27Glu polymorphism between diabetic and control groups in this study. CONCLUSIONS: In a Taiwanese population, homozygosity of Arg16 in the ADRB2 gene was associated with a higher frequency (odds ratio 1.87, 95% confidence interval 1.34-2.40) for development of type 2 diabetes. Moreover, this polymorphism was also associated with an earlier onset of type 2 diabetes. However, the Glu27Gln polymorphism had no impact on either BMI or type 2 diabetes in a Taiwanese population.     

亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态与结直肠癌(CRC)遗传易感性的关系.方法:采用TaqMan方法检测CRC 449例与对照672例的MTHFR C677T的基因型分布及差异.以非条件Logistic回归法计算表示相对危险度的比值比(OR)及其95%可信区间(CI).OR值均经性别、年龄、吸烟、饮酒、体质量指数和一级亲属CRC家族史等因素校正.结果:CRC组677T等位基因频率显著低于对照组,其为CRC发生的保护因素(OR:0.70,95%CI:0.58-0.83,P<0.01).与CC纯合子相比,CT杂合子的CRC风险显著降低至0.73倍(95%CI:0.56-0.95,P<0.05),而TT纯合子的CRC风险进一步降至0.47倍(95%CI:0.33-0.68,P<0.01).在非饮酒人群中,C677T的CRC风险保护效应略有增强;而在饮酒人群中,CT和TT基因型携带者的CRC发病风险虽仍低于CC基因型携带者,但差异无统计学意义.在CRC人群中,荷大肿瘤(最大直径>4cm)者携带TT基因型的比例高于荷小肿瘤者(16.3% vs 8.3%,P<0.05);荷黏液腺癌者携带TT基因型的比例高于荷乳头状腺癌及管状腺癌者(22.2% vs 17.1%,10.3%,P=0.084).结论:MTHFR C677T降低CRC发病风险,饮酒可能削弱该多态的CRC风险保护效应.TT基因型可能与CRC肿瘤进展有关.     

糖尿病与结直肠癌患病危险关系的调查分析

目的:了解糖尿病(DM)与结直肠癌患病的关系,明确糖尿病相关因素对结直肠癌发病的影响.方法:采用病例对照的方法分析同时期住院的结直肠癌(n=364)与非肿瘤患者(n=733)与糖尿病相关因素的关系及差异.对比分析两组患者的糖尿病患病情况、糖尿病家族史、结直肠癌家族史、并发病情况、吸烟、饮酒等生活行为以及血脂水平等方面的差异.结果:结直肠癌组糖尿病患者患结直肠癌的危险度是非糖尿病患者的1.72倍,有糖尿病家族史者患结直肠癌的危险度也明显增加(OR=1.64);有结直肠癌家族史的糖尿病患者患结直肠癌的风险度(OR=3.23)高于无结直肠癌家族史的糖尿病患者(OR=1.57);但通过进一步分层分析表明无论患者有无结直肠癌家族史,结直肠癌组糖尿病患者所占比例均高于对照组.多因素回归分析显示:年龄、性别、糖尿病家族史、冠心病、高血压、吸烟、饮酒及血脂对结直肠癌没有显著影响;糖尿病及结直肠癌家族史对结直肠癌患病具有显著影响(OR=2.99,P＜0.01;OR=1.79,P＜0.01).结论:糖尿病与结直肠癌患病存在一定的相关性,糖尿病增加了患结直肠癌的风险性,其是结直肠癌患病的独立危险因素.