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Biomedical subjects

Kun Chen

Publications and source records attributed to Kun Chen.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide metabolism using oligonucleotide genotyping microarray].

AIM: To investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide. METHODS: An oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC. RESULTS: CYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1. CONCLUSION: CYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

[Concept on the use of "number needed to be exposed" in epidemiology].

OBJECTIVE: To introduce the concept, methods for calculation and application of "number needs to be exposed (NNE)" in Epidemiological studies. METHODS: Data was analyzed from a study on the association between diaspirin cross-linked hemoglobin (DCLHb) with 28-day mortality in patients with severe traumatic hemorrhagic shock. RESULTS: The crude "number needed to be exposed for one additional person to be harmed" (NNEH) was 3.7 (95% CI: 2.2-11.5) for the exposure to DCLHb. After controlling the confounding bias of the baseline mortality risk, the adjusted NNEH became 2.6 (95% CI: 1.6-8.0) id., on average, among 2.6 patients exposed to DCLHb, one additional case of death would have developed within 28 days after initial hospitalization if the distribution of baseline mortality risk in exposed group had been equal to that in the unexposed group. CONCLUSION: NNE could be expressed as the estimated average number of persons needed to be exposed for contributing (either developing or preventing for) one additional case of disease or death in a prospective study when compared with the unexposed persons. As a new index for measuring the absolute effect of an exposure, NNE presented the results on epidemiological studies in a more intuitive and understandable manner. Consequently, this method could be favorably accepted by clinicians, health policy makers and the public.

Epidemiologic Studies↗
PubMed2005

[A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer].

OBJECTIVE: To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC). METHODS: Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls. RESULTS: The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10). CONCLUSION: CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.

Alleles↗
PubMed2005

[Glutathione S-transferase M1 polymorphism and the risk on colorectal cancer: a multilevel meta regression].

OBJECTIVE: In order to investigate the relationship between Glutathione S-transferase M1 (GSTM1) status and the risk on colorectal cancer as well as to detect the related factors to this association. METHODS: A pooled analysis of multilevel Meta-regression was performed to estimate GSTM1 deficiency associated with the risks of colorectal cancer. Then subgroup Meta-regression was undertaken to evaluate the possible relationship between heterogeneity and the related characteristics. RESULTS: The overall pooled odds ratios of colorectal cancer risk associated with GSTM1 deficiency was 1.17 (95% CI: 1.08-1.26). Ethnicity, percent of GSTM1 deficiency in population had significant relationships with heterogeneity across the studies (P < 0.05). Results of subgroup Meta-regression showed that GSTM1 deficiency was significantly associated with colorectal cancer risk in ethnic subgroups of Asians, Caucasians and in low level (lower than 50%) of GSTM1 deficiency population (P < 0.05). The respective pooled ORs were 1.14, 1.25 and 1.29. CONCLUSION: GSTM1 deficiency seemed to be a risk factor for colorectal cancer, while interactions on the characteristics of ethnicity, percentage of GSTM1 deficiency in the studied population were related to this association.

Asian People↗
PubMed2004

A hidden Markov modeling approach for admixture mapping based on case-control data.

Admixture mapping is potentially a powerful method for mapping genes for complex human diseases, when the disease frequency due to a particular disease-susceptible gene is different between founding populations of different ethnicity. The method tests for association of the allele ancestry with the disease. Since the markers used to define ancestral populations are not fully informative for the ancestry status, direct test of such association is not possible. In this report, we develop a unified hidden Markov model (HMM) framework for estimating the unobserved ancestry haplotypes across a chromosomal region based on marker haplotype or genotype data. The HMM efficiently utilizes all the marker data to infer the latent ancestry states at the putative disease locus. In this HMM modelling framework, we develop a likelihood test for association of allele ancestry and the disease risk based on case-control data. Existence of such association may imply linkage between the candidate locus and the disease locus. We evaluate by simulations how several factors affect the power of admixture mapping, including sample size, ethnicity relative risk, marker density, and the different admixture dynamics. Our simulation results indicate correct type 1 error rates of the proposed likelihood ratio tests and great impact of marker density on the power. The simulation results also indicate that the methods work well for the admixed populations derived from both hybrid-isolation and continuous gene-flowing models. Finally, we observed that the genotype-based HMM performs very similarly in power as the haplotype-based HMM when the haplotypes are known and the set of markers is highly informative.

Alleles↗
PubMed2004

Correction of defective early tyrosinase processing by bafilomycin A1 and monensin in pink-eyed dilution melanocytes.

Mutations in the human P gene result in oculocutaneous albinism type 2, the most common form of albinism. Mouse melan-p1 melanocytes, cultured from mice null at the homologous pink-eyed dilution (p) locus, exhibit defective melanin production. A variety of compounds including tyrosine, NH4Cl, bafilomycin A1, concanamycin, monensin, and nigericin are capable of restoring melanin synthesis in these cells. In the current study, we investigated the subcellular effects of bafilomycin A1 and monensin treatment of melan-p1 cells. Both agents play two roles in the processing of tyrosinase (Tyr) in melan-p1 cells. First, combined glycosidase digestion and immunoblotting analysis showed that these agents reduce levels of Tyr retained in the endoplasmic reticulum (ER) and facilitate the release of Tyr from the ER to the Golgi. Secondly, treatment with these compounds resulted in the stabilization of Tyr. Surprisingly, induction of melanin synthesis corresponds more closely with diminution of ER-retained Tyr, rather than the absolute amount of Tyr. Our results suggest that bafilomycin A1 and monensin induce melanin synthesis in melan-p1 cells mainly by facilitating Tyr processing from the ER to the Golgi by increasing the pH in either the ER or the ER-Golgi intermediate compartment.

Animals↗
PubMed2004

[Alcohol drinking and colorectal cancer: a population-based prospective cohort study].

OBJECTIVE: To understand the incidence of colorectal cancer in population drinking or not and to validate the relationship between drinking and colorectal cancer. METHODS: The data obtained from a questionnaire used in a population-based prospective screenings study in ten countries of Jiashan County was examined. A total of 64,102 men and women aged 30 y and older without history of cancer at baseline and a subcohort of 29,044 of them drinking past and current was conducted. Cox regression model was applied to estimate relative risk (RR). RESULTS: After 10 years follow-up,107 colon cancer and 135 rectal cancer cases were identified. Among drinkers and abstainers, the incidence density of colorectal cancer was 36.18 per 100 thousand and 37.26 per 100 thousand, respectively and there wasn't statistical significance(Z=0.52, P>0.05); The crude RR (95%CI) for drinker compared with never drinkers was 0.97(0.75 approximately 1.25), and the multivariable-adjusted RR (95%CI) was 1.13(0.87 approximately 1.48). The research power of this study was 96.99%. CONCLUSION: Alcohol drinking isn't one of the risk factors of colorectal cancer among Jiashan County population.

Adult↗
PubMed2004

[Association of drinking water source and colorectal cancer incidence: a prospect cohort study].

BACKGROUND & OBJECTIVE: The pollution of drinking water, for example river and pool, has long been recognized to be associated with an increased risk of colorectal cancer (CRC) in previous epidemiological studies. There is little prospect cohort study with person-years directly on the relative risks of different sources of drinking water for CRC. METHODS: From May 1989 to April 1990, a screening for CRC was carried out among residents aged 30 and over 30 years in 10 villages and towns of Jiashan in China. A total of 64115 residents who participated the screening were classified into 5 cohorts by the source of drinking water and were followed-up for CRC incidence through a tumor reporting system including a rapid reporting system of CRC Registry and for death instance through Death Registration of Jiashan. After 11 years of follow-up, person-years calculated with every cohort member, the incidence densities of CRC with different sources of drinking water were analyzed respectively. Poisson regression was used to control potential confounding variables including demography variables and smoke history and to attain crude and adjusted relative risks based on person-years. RESULTS: A trend was seen toward increasing incidence rates of colorectal cancer from municipal, river, channel, mixed water to well source in turn as shown as 29.61, 32.67, 33.45, 40.87, 58.67 per 100,000 inhabitants, and only the role in risk of well water was marked different from municipal water (P< 0.05). After adjusted the confounding variables by multi-Poisson regression, we found the significant risk of drinking well water for colon cancer, rectal cancer, and colorectal cancer. The relative risks were 1.741 (95%CI 1.001-3.029), 2.228 (95%CI 1.432-3.466), and 2.022 (95%CI 1.432-2.854), respectively. CONCLUSION: Drinking well water long is a risk factor for colorectal cancer in Jiashan, especially for rectal cancer.

Adult↗
PubMed2004

[Genetic polymorphism in cytochrome P450 2E1, salted food and colorectal cancer susceptibility: a case-control study].

OBJECTIVE: To investigate PstI allelic variants of cytochrome P450 2E1 (CYP2E1), the interaction effect on salted food and their role in risk for colorectal cancer. METHODS: The genotypes of CYP2E1 PstI restriction fragment length polymorphism were analyzed in 126 colorectal cancer cases and 343 normal controls. The unconditional logistic regression was applied to estimate the OR and its 95% CI. RESULTS: The CYP2E1 C1/C1, C1/C2 and C2/C2 genotypes were found respectively in 61.8%, 35.8% and 2.4% of normal control, similar to rectal cancer cases. The percentage of PstI variant genotype (54.9%: 52.9% C1/C2 and 2.0% C2/C2) in colon cancer cases was significantly higher than that in controls (adjusted OR1.979, 95% CI 1.090 approximately 3.595). Stratified analysis suggested an interaction between CYP2E1 C2 allele and salted food. The odds ratio (OR) for the CYP2E1 variant genotype, salted food eaten weekly or biweekly and eaten every day or every other day were 1.935, 2.122 and 2.315, respectively, while those of salted food combined with variant genotype eaten weekly or biweekly and eaten every day or every other day were 2.272 and 3.127. The role in risk for rectal cancer was different from that for colon cancer. Whatever the CYP2E1 genotype is, the risk for rectal cancer came to marked when salted food was consumed weekly or biweekly (OR = 2.646 and 2.297, respectively). However, none but the combined effect of variant genotype and salted food eaten every day or every other day had the notably risk for colon cancer and the odds ratio suddenly increased to 4.262 (95% CI 1.395 approximately 13.017), 1.69-fold higher than that of wild genotype (P = 0.072). CONCLUSION: The CYP2E1 C2 allele is a susceptibility factor for colorectal cancer, especially for colon cancer, and there is an apparent gene-environment interaction between the susceptible genotype and salted food.

Alleles↗
PubMed2004

[Characteristics of virulence gene in Vibrio parahaemolyticus strains isolated from clinical patients and environment in Hangzhou, China].

OBJECTIVES: To investigate the characteristics of virulence gene in Vibrio parahaemolyticus strains isolated from clinical patients and environment in Hangzhou, China. METHODS: Thermostable direct hemolysin gene (tdh) and thermostable direct hemolysin-related hemolysin gene (trh) were determined in a total of 174 strains of V. parahaemolyticus isolated from patients and environment (seafood) in Hangzhou area by PCR. RESULTS: The tdh was found in 92 out of 94 V. parahaemolyticus strains from food poisoning patients and in 33 out of 34 strains from sporadic diarrhea patients, and trh was not detected in all above clinical strains. Meanwhile the tdh was negative in all V. parahaemolyticus strains from environment, and the trh was also negative except one strain with urease activity. All strains with trh negative had no the activity of urease. CONCLUSIONS: The V. parahaemolyticus strains from food poisoning patients and sporadic diarrhea patients are tdh positive and trh negative. The V. parahaemolyticus strains with tdh negative and almost trh positive in environment might be a potential pathogen in Hangzhou.

Bacterial Proteins↗
PubMed2004

[Relationship between organochlorine pollution in soil and rice and the incidence of colorectal cancer in Jiashan county, Zhejiang province].

OBJECTIVE: To study the relationship between organochlorine and colorectal cancer. METHODS: With multistage cluster random sampling, 11 towns were drawn based on the standardized incidence of colorectal cancer. Administrative and natural villages were drawn subsequently. Rice and soil samples in the paddy fields were collected in the villages. The contents of organochlorine were detected. Rank correlation analysis was performed together with the data of colorectal cancer incidence. RESULTS: The contents of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) in both rice and soil samples were below the amounts of the country. Statistics showed that the standardized incidence rates were significantly different among the 11 towns. The contents of delta-HCH, gamma-HCH, sodium pentachlorophenate in rice and those of delta-HCH in soil were statistically different among the towns through the rank sum test. The standardized incidence of colorectal cancer was significantly connected with the content of total DDT in rice while rectal cancer with total DDT and PP'-DDE and colon cancer with 1245 of polychlorinated biphenyl (PCBs). The correlation coefficients were 0.636, 0.691, 0.716 and 0.658 respectively (P < 0.05). CONCLUSIONS: Rectal cancer was statistically correlated with organochlorine, mainly for total DDT and dichlorodiphenyldichloroethylene (PP'-DDE). Colon cancer was significantly associated with 1245 of PCBs. Further study should be performed since this research was only an ecological study.

Adult↗
PubMed2004

[A case-control study on the relationship between nutrition and gastric cancer in islanders].

OBJECTIVE: To study the association between nutritional factors and gastric cancer in islanders. METHODS: A population-based case-control study on diet and gastric cancer was carried out in Zhoushan islands, China. 103 cases of gastric cancer newly diagnosed in 2001 and 133 controls frequency-matched by age, sex, and islands of residence among residents in Zhoushan were included in the study. Dietary intake was estimated using a constructed food frequency questionnaire. Total calories and 15 nutrients were calculated according to the food composition table and their adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by gender using unconditional logistic regression models. RESULTS: Increased risks of gastric cancer were associated with protein (ORQ4 vs. Q1=10.3; P for linear trend=0.01), saturated fat (ORQ4 vs. Q1=3.24), and cholesterol (ORQ4 vs. Q1=2.76) particularly among males. Among females, carbohydrate was a significant high-risk nutrient (ORQ4 vs. Q1=14.8; P for linear trend=0.024). In both sexes, all cases reported a significantly higher daily intake of natrium mainly from salts than controls. An inversed association with the risk of gastric cancer was seen in vitamin A and vitamin C. CONCLUSION: The findings from this study provided information about the role of specific nutrients in the etiology of gastric cancer. High intakes of protein, saturated fat, cholesterol, sodium and poor intakes of vitamin A and C could increase the risk of gastric cancer.

Adult↗
PubMed2004

[A case-control study on the polymorphisms of methylenetetrahydrofolate reductases, drinking interaction and susceptibility in colorectal cancer].

OBJECTIVE: To investigate the relationship between methylenetetrahydrofolate reductases (MTHFR) polymorphisms and colorectal cancer susceptibility. METHODS: A case-control study of 126 patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298C polymorphisms in colorectal cancer development. Genotypes of C677T and A1298C polymorphisms were analyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The frequencies of MTHFR 677T and 1298C allele were 39.7% and 17.1%, respectively. After adjustment for age and sex, the MTHFR 1298C alleles seemed to have reduced association on the risk of colorectal cancer comparing to wild types. Among those with 677T and 1298A alleles, a decreased risk of colorectal cancer was observed: a 4-fold decrease in colorectal cancer risk (OR = 0.552, 95% CI: 0.265 - 1.150) in those with 677T and 1298C alleles. Men who were ex-drinkers and with MTHFR 1298C allele had a 2-fold increase in risk of colorectal cancer (OR = 3.307, 95% CI: 0.521 - 17.698) while no increased risk was seen among those current-drinkers. CONCLUSIONS: This study suggested that certain MTHFR C677T and A1298C might be associated with the risk of colorectal cancer development. The interaction between MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectal cancer.

Adult↗
PubMed2004

[Associations between genetic polymorphisms of glutathione S-transferase M1 and T1, smoking and susceptibility to colorectal cancer: a case-control study].

OBJECTIVE: To evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer. METHODS: A case-control study of 126 patients and 343 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR). RESULTS: The frequencies of GSTM1 null and GSTT1 null genotypes were 55.5% and 20.4%, respectively. After adjustment for age and sex, among those with GSTT1 null genotype, the GSTM1 null genotype had a significant increased risk of rectal cancers compared to GSTM1 non-null genotype (OR=9.74, 95% CI, 1.13 - 83.85). A 2.22-fold risk of colon cancers was associated with GSTM1 null genotype compared to GSTM1 non-null genotype among current smokers (P >0.05). Individuals with GSTT1 null genotype and currently smoking had a significant risk of colon cancers (OR = 4.55, 95% CI, 1.14 - 18.17), and rectal cancers (OR = 4.60, 95% CI, 1.11 - 19.11). CONCLUSION: This study suggests that certain null GSTM1 and GSTT1 genotypes may be associated with an elevated risk of colorectal cancer which may be modified by interaction of the two genetic polymorphisms and cigarette smoking.

Adult↗
PubMed2003

Histamine elicits neuronal excitatory response of red nucleus in the rat via H2 receptors in vitro.

Perfusing slices with histamine (1-100 microM) produced an excitatory response in rat rubral neurons (118/132, 89.4%). The histamine-induced excitation was not blocked by the low-Ca2+/high-Mg2+ medium (n=10), supporting a direct postsynaptic action of the amine. Histamine H2 receptor antagonist ranitidine effectively blocked the excitatory response of rubral neurons to histamine (n=26), but H1 receptor antagonist triprolidine did not (n=24). The excitatory effect of histamine could be mimicked by dimaprit, a highly selective H2 receptor agonist (n=24), and the dimaprit-elicited excitation of the rubral neurons could be blocked by ranitidine (n=16), but not by triprolidine (n=9). In addition, H1 receptor agonist 2-pyridylethylamine could not elicit any response in rubral neurons (n=12). These results indicate that histamine excites red nucleus neurons through H2 receptors and suggest that the histaminergic afferent fibers may play an important functional role in the sensorimotor integration through the red nucleus.

Animals↗
PubMed2003

Cluster randomization trial of sequence mass screening for colorectal cancer.

PURPOSE: Colorectal cancer is a major cause of death worldwide. To reduce the incidence and mortality from rectal cancer, an individual quantitative risk-assessment model (hereafter referred to as the Attributive Degree Value) and reverse passive hemagglutination fecal occult blood test were used in a randomized, controlled, population-based trial that was conducted in Jiashan County, People's Republic of China. METHODS: All residents of Jiashan County aged 30 years or older were enrolled in the study, and 21 townships in the county were randomized to either a screening (n = 10 townships) or control (n = 11 townships) group. Participants in the screened group submitted a one-article-per-slide stool sample and completed a structured risk-assessment questionnaire from which their attributive degree value was computed. According to study protocol, 4,299 participants were defined as high risk and underwent diagnostic evaluation with 60-cm flexible sigmoidoscopy and, in some cases, an additional screening with colonoscopy. RESULTS: From 1989 to 1996, cumulative mortality from colon cancer was 90 (95 percent confidence interval, 83-97) per 100,000 in the screened group and 83 (95 percent confidence interval, 76-90) per 100,000 in the control group (log-rank P = 1.49, P = 0.222). Mortality from rectal cancer during this time was 110 (95 percent confidence interval, 102-118) per 100,000 in the screened group, which differed significantly from the control group mortality rate of 161 (95 percent confidence interval, 152-170) per 100,000 (log-rank P = 0.003). CONCLUSION: Mass screening with a reverse passive hemagglutination fecal occult blood test along with an individual attributive degree value score was effective in reducing mortality from rectal cancer but not in reducing mortality from colon cancer or the incidence of colorectal cancer.

Adult↗
PubMed2003

Non-parametric hypothesis testing and confidence intervals with doubly censored data.

The non-parametric maximum likelihood estimator (NPMLE) of the distribution function with doubly censored data can be computed using the self-consistent algorithm (Tumbull, 1974). We extend the self-consistent algorithm to include a constraint on the NPMLE. We then show how to construct confidence intervals and test hypotheses based on the NPMLE via the empirical likelihood ratio. Finally, we present some numerical comparisons of the performance of the above method with another method that makes use of the influence functions.

Algorithms↗