Biomedical subjects

Wen Tan

Publications and source records attributed to Wen Tan.

62 records · Page 4Linked to original sources

PubMed2002

Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population.

Esophageal squamous cell carcinoma (ESCC), which is prevalent in China, is believed to be induced by environmental carcinogens. Accumulating evidence has shown that individual variation in DNA repair capacity resulting from genetic polymorphism influences risk of environmental carcinogenesis. We therefore investigated the associations between genetic polymorphisms in the DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) and risk of ESCC in an at-risk Chinese population. Genotypes were determined by a PCR-based approach in 433 patients with ESCC and 524 frequency-matched normal controls. We found that individuals with Trp/Trp genotype at XRCC1 Arg194Trp site had a 2-fold increased risk of this disease compared to Arg/Arg genotype (adjusted OR = 1.98; 95% CI 1.26-3.12). Furthermore, when compared to Arg/Arg and Arg/Trp genotype combined, homozygote for Trp/Trp genotype significantly increased the risk of developing ESCC, with the adjusted OR being 2.07 (95% CI 1.34-3.20). However, the XRCC1 Arg399Gln polymorphism was not significantly associated with risk of ESCC, with the adjusted OR being 0.87 (95% CI 0.55-1.37). Neither Asp312Asn nor Lys751Gln polymorphisms in the XPD gene influenced risk of ESCC in our study. These findings suggest that DNA repair gene XRCC1 but not XPD might play a role in esophageal carcinogenesis and might represent a genetic determinant in the development of the cancer.

Age Factors↗

PubMed2002

[Single nucleotide polymorphisms in methylenetetrahydrofolate reductase gene and susceptibility to cancer of the gastric cardia in Chinese population].

OBJECTIVE: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism that affects DNA methylation and synthesis, and the risk of adenocarcinoma of the gastric cardia (AGC). METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 205 patients with AGC and 360 age-and-sex-matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR genes C6677T and A1298C and the relation between these genotypes and risk of AGC was analyzed. RESULTS: The genotype frequency of MTHFR C677CC was 35.0% among the controls and was 20.5% among the AGC patients; the genotype frequency of 677CT was 47.8% among the controls and 50.7% among the AGC patients, and the genotype frequency of 677TT was 17.2% among the controls and 28.8% among the AGC patients % (chi(2) = 17.63, P = 0.0002). The individuals with 677CT genotype or 677TT genotype had a 1.76-fold [95% confidence interval (CI), 1.13 - 2.76] or 2.97-fold (95% CI, 1.75 - 5.05) increased risk of developing AGC compared with those who had 677CC genotype. The distribution of MTHFR A1298C genotype was not significantly different between the two groups (chi(2) = 0.08, P = 0.96). The value of odd ratio (OR) in the individuals with 677CT//1298AA genotype (95% CI, 1.48 approximately 6.48), and the value of OR in the individuals with 677CT/1298CC genotype was 17.00 (95% CI, 1.26 approximately infinity; P = 0.042). CONCLUSION: Single nucleotide polymorphism in the MTHFR gene is a risk factor of carcinogenesis of AGC in the Chinese population. Although the MTHFR A1298C polymorphism was not associated with AGC, The risk of developing AGC in the individuals with MTHFR677CT/1298CC was 17 times higher than that in the individuals with MTHFR677CC/1298AA, thus showing that a joint effect exists between the MTHFR 677 and 1298 polymorphisms on the risk of AGC.

Adenocarcinoma↗

PubMed2002

Polymorphisms of the DNA repair gene XPD and risk of lung cancer in a Chinese population.

Previous studies suggested that suboptimal DNA repair capacity is associated with cancer risk and that the Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may influence DNA repair capacity. We therefore tested the hypothesis that these two XPD polymorphisms are associated with susceptibility to lung cancer in a hospital-based, case-control study in a Chinese population. Genotypes were determined by polymerase chain reaction-based restriction fragment length polymorphism methods in 383 healthy controls and 351 patients with lung cancer. We found that those who carried at least one 312Asn variant allele had an increased risk of squamous cell carcinoma (SCC) of the lung compared with those with the 312Asp/Asp genotype (adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.10-2.96). Compared with those having the 751Lys/Lys genotype, subjects carrying at least one variant 751 Gln allele were at a borderline increased risk of SCC of the lung (adjusted OR, 1.52; 95% CI, 0.94-2.46). Furthermore, stratified analysis suggested a multiplicative interaction between tobacco smoking and the Asp312Asn polymorphism on risk of SCC of the lung. The adjusted ORs of SCC of the lung for the variant XPD 312Asn genotype alone, for smoking > or = 29 pack-years alone, and for both the factors combined were 1.04 (95% CI, 0.37-2.94), 4.74 (95% CI, 2.88-9.49), and 14.32 (95% CI, 5.80-35.2), respectively. Similar results were evident for the Lys751Gln polymorphism that was in the linkage disequilibrium with the variant 312Asn allele. These data suggest that the two polymorphisms in the XPD gene may influence risk of smoking-related SCC of the lung.

Aged↗

PubMed2002

Susceptibility to gastric cardia adenocarcinoma and genetic polymorphisms in methylenetetrahydrofolate reductase in an at-risk Chinese population.

Methylenetetrahydrofolate reductase (MTHFR) plays a centralrole in converting folate to methyl donor for DNA methylation, an epigenetic modification known to be dysregulated in carcinogenesis. Our previous study revealed that MTHFR polymorphisms contribute to a great risk of esophageal cancer in a Chinese population. This case-control study was to examine the association between MTHFR polymorphisms and gastric cardia adenocarcinoma (GCA), which is also prevalent in high-risk areas of esophageal cancer and thus may share common etiological factors with esophageal cancer in this population. The study subjects were 217 patients with GCA and 468 population controls matched on sex and age. The MTHFR C677T and A1298C genotypes were detected by a PCR-based RFLP assay. It was found that subjects with the MTHFR 677TT variant genotype had a 2-fold increased risk of GCA (odds ratio, 2.04; 95% confidence interval, 1.28-3.26). Moreover, a significantly elevated risk was also seen among the MTHFR 677CT heterozygotes (odds ratio, 1.56; 95% confidence interval, 1.03-2.36). The MTHFR A1298C polymorphism had no effect on risk of GCA. These findings are generally consistent with our initial observation for esophageal cancer and suggest that the MTHFR genotype may be a determinant of GCA among this at-risk Chinese population.

Adenocarcinoma↗

PubMed2002

[Study on the association between smoking behavior and dopamine receptor D2 gene polymorphisms among lung cancer cases].

OBJECTIVE: To investigate the possible association between dopamine D2 receptor (DRD2) TaqI A and TaqI B genotypes as well as smoking behavior and the risk of lung cancer among Chinese Han people. METHODS: PCR was used to perform genotyping on peripheral WBC DNA from 326 lung cancer patients and 326 age, sex and ethnicity-matched healthy controls. Subjects were interviewed to obtain relevant information and lifetime history of tobacco use. RESULTS: There were no statistically significant differences in the distribution of DRD2 genotypes between lung cancer cases and controls. The DRD2 genotypes and smoking status showed no correlation among cases and among controls as well. However, among controls, the frequency of the DRD2 * A2/A2 genotype in smokers who smoked > or = 25 cigarettes/day appeared to be higher than that in those who smoked < 25 cigarettes/day (42.5% versus 26.1%, P = 0.047). A similar trend was also found for the DRD2 * B2/B2 genotype, which was linked to the DRD2 * A2/A2 genotype, although the difference was not significant (40.0% versus 26.1%, P = 0.091). In contrast to controls, no association was found between the DRD2 genotypes and smoking among lung cancer cases. CONCLUSION: Our results suggested that DRD2 * A2/A2 genotype might be associated with a greater smoking intensity in Chinese. Further studies are needed to confirm this preliminary finding.

Aged↗

PubMed2002

[Lung cancer risk associated with genetic polymorphism in myeloperoxidase (-463 G/A) in a Chinese population].

OBJECTIVE: To examine the relationship between susceptibility to lung cancer among Chinese and genetic polymorphism at nucleotide -463 (G/A) in myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes and involved in the formation of hydroxyl radicals and activation of various smoking-related carcinogens. METHODS: The association of this polymorphism with lung cancer in a hospital-based case-control study of 314 patients and 320 age- and sex-matched controls was tested. The MPO genotypes were determined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). RESULTS: The allele frequency for MPO-463A was found to be 11.0% for controls, compared with 15.0% for patients. Multivariate analysis showed an increased risk for overall lung cancer in subjects having GG genotype (OR, 1.7; 95% CI, 1.2 - 2.5), however, the elevated risk was limited to squamous cell carcinoma (OR, 2.4; 95% CI, 1.4 - 3.9; n = 177) but not to adenocarcinoma (OR, 1.3; 95% CI, 0.8 - 2.1; n = 137). In addition, the risky effect of the GG genotype on squamous cell carcinoma of the lung was evident only in the smokers and those who smoked >/= 26 pack-years (OR, 20.5; 95% CI, 5.6 - 75.3) as compared with GA and AA genotypes (OR, 6.2; 95% CI, 1.7 - 22.5) but not in the nonsmokers or those who smoked < 26 pack-years. CONCLUSION: Our data support the hypothesis that -463A polymorphism in the MPO gene may reduce the susceptibility to lung cancer in the Chinese.

Asian People↗

PubMed1999

Chemoprevention of 2-amino-1-methyl-6-phenyli-midazo 4,5-b pyridine-induced carcinogen-DNA adducts by Chinese cabbage in rats.

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 (P< 0.01). 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.

Journal Article↗

PubMedDate not supplied

Genetic polymorphisms and susceptibility to esophageal cancer among Chinese population (review).

Esophageal cancer, which is prevalent in China and some other parts of the world, is a complex disease likely resulting from polymorphisms of multiple interacting genes and gene-environment interactions. Recent efforts have been made to analyze the associations between risk of this cancer and hereditary sequence variations in genes involved in metabolism, DNA repair and cell cycle control. We summarized here the results of published case-control studies that have examined the effects of common alleles of 15 genes, MTHFR, CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTT1, GSTP1, NAT2, XRCC1, XPD, hOGG1, MGMT, p53, CNDD1 and L-Myc, on risk of esophageal squamous cell carcinoma among Chinese. Statistically significant differences in genotype frequencies found in case-control comparisons were MTHFR C677T and A1298C polymorphisms, the XRCC1 Arg194Trp polymorphisms, the hOGG1 Ser326Cys polymorphism, and the p53 Arg72Pro polymorphism. The overall effects of these genetic polymorphisms were moderate in terms of relative risk, with ORs ranging from 2-10. There was also some evidence that genetic polymorphisms in certain carcinogen-metabolizing enzymes such as CYP2E1, CYP1A1, CYP2A6, GSTM1, and GSTP1 modulate risk of the cancer, although the results require confirmation with larger sample size studies. For polymorphisms in GSTT1, XPD, CCND1, and L-Myc, the risk estimate from the studies was sufficiently precise to exclude an OR >/=1.5.

Carcinogens↗