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Biomedical subjects

Ping Su

Publications and source records attributed to Ping Su.

18 recordsLinked to original sources

Chromophore attachment to phycobiliprotein beta-subunits: phycocyanobilin:cysteine-beta84 phycobiliprotein lyase activity of CpeS-like protein from Anabaena Sp. PCC7120.

The gene alr0617, from the cyanobacterium Anabaena sp. PCC7120, which is homologous to cpeS from Gloeobacter violaceus PCC 7421, Fremyella diplosiphon (Calothrix PCC7601), and Synechococcus sp. WH8102, and to cpcS from Synechococcus sp. PCC7002, was overexpressed in Escherichia coli. CpeS acts as a phycocyanobilin: Cys-beta84-phycobiliprotein lyase that can attach, in vitro and in vivo, phycocyanobilin (PCB) to cysteine-beta84 of the apo-beta-subunits of C-phycocyanin (CpcB) and phycoerythrocyanin (PecB). We found the following: (a) In vitro, CpeS attaches PCB to native CpcB and PecB, and to their C155I-mutants, but not to the C84S mutants. Under optimal conditions (150 mm NaCl and 500 mm potassium phosphate, 37 degrees C, and pH 7.5), no cofactors are required, and the lyase had a Km(PCB) = 2.7 and 2.3 microm, and a kcat = 1.7 x 10(-5) and 1.1 x 10(-5) s(-1) for PCB attachment to CpcB (C155I) and PecB (C155I), respectively; (b) Reconstitution products had absorption maxima at 619 and 602 nm and fluorescence emission maxima at 643 and 629 nm, respectively; and (c) PCB-CpcB(C155I) and PCB-PecB(C155I), with the same absorption and fluorescence maxima, were also biosynthesized heterologously in vivo, when cpeS was introduced into E. coli with cpcB(C155I) or pecB(C155I), respectively, together with genes ho1 (encoding heme oxygenase) and pcyA (encoding PCB:ferredoxin oxidoreductase), thereby further proving the lyase function of CpeS.

Anabaena↗

Induction of renal cytochrome P450 arachidonic acid epoxygenase activity by dietary gamma-linolenic acid.

Dietary gamma-linolenic acid (GLA), a omega-6 polyunsaturated fatty acid found in borage oil (BOR), lowers systolic blood pressure in spontaneously hypertensive rats (SHRs). GLA is converted into arachidonic acid (AA) by elongation and desaturation steps. Epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 (P450)-derived AA eicosanoids with important roles in regulating blood pressure. This study tested the hypothesis that the blood pressure-lowering effect of a GLA-enriched diet involves alteration of P450-catalyzed AA metabolism. Microsomes and RNA were isolated from the renal cortex of male SHRs fed a basal fat-free diet for 5 weeks to which 11% by weight of sesame oil (SES) or BOR was added. There was a 2.6- to 3.5-fold increase in P450 epoxygenase activity in renal microsomes isolated from the BOR-fed SHRs compared with the SES-fed rats. Epoxygenase activity accounted for 58% of the total AA metabolism in the BOR-treated kidney microsomes compared with 33% in the SES-treated rats. More importantly, renal 14,15- and 8,9-EET levels increased 1.6- to 2.5-fold after dietary BOR treatment. The increase in EET formation is consistent with increases in CYP2C23, CYP2C11, and CYP2J protein levels. There were no differences in the level of renal P450 epoxygenase mRNA between the SES- and BOR-treated rats. Enhanced synthesis of the vasodilatory EETs and decreased formation of the vasoconstrictive 20-HETE suggests that changes in P450-mediated AA metabolism may contribute, at least in part, to the blood pressure-lowering effect of a BOR-enriched diet.

Animals↗

Detection and quantification of Bifidobacterium lactis LAFTI B94 in human faecal samples from a consumption trial.

A method was developed to allow detection of the probiotic Bifidobacterium lactis LAFTI B94 in human clinical samples. A new probe, Laf94p, was developed to accomplish colony hybridization of B. lactis B94. PCR detection of B94 was also achieved using the species-specific (B. lactis) primer pair. These tests and probes allowed detection and quantification of B94 in the human intestinal flora. The sensitivity of the probe was assessed by monitoring faecal levels of B94 in humans who were fed the culture. In this trial, five volunteers were fed with the probiotic. The presence of B94 was assessed daily. Viable B94 could be detected at high levels (as high as 1.8 x 10(9) cfu g(-1) wet weight) during the feeding period. Four weeks after the feeding stopped, B94 could still be detected in one subject. These results indicate that B94 survives in the human gastrointestinal tract.

Adult↗

Development and application of a multi-target immunoaffinity column for the selective extraction of natural estrogens from pregnant women's urine samples by capillary electrophoresis.

In this paper, a methodology for the determination of three naturally occurring estrogens (estradiol, estrone and estriol) in pregnant women's urine has been described. The procedure included immunoaffinity column (IAC) extraction of 4 mL of urine sample and subsequent analysis of the extraction by micellar electrokinetic chromatography (MEKC). A multi-target polyclonal antibody that has high affinity to three estrogens was produced. Then the IAC was developed by coupling polyclonal antibody to CNBr-activated Sepharose 4B. The IAC showed high affinity for these estrogens. Recoveries of three estrogens from human serum matrix were greater than 92% with R.S.D. less than 4.5%. The final elute of urine sample was diluted with running buffer and then quantitated with MEKC. The experimental results demonstrated that IAC was a useful technique for extraction and concentration of estrogens from biological samples. Three estrogens levels in six pregnant women's urine were measured by both the present method and enzyme-linked immunoadsorbent assay (ELISA). The results of this method have been found to correlate well with those of ELISA.

Chromatography, Affinity↗

Reconstitution of phycobilisome core-membrane linker, LCM, by autocatalytic chromophore binding to ApcE.

The core-membrane linker, LCM, connects functionally the extramembraneous light-harvesting complex of cyanobacteria, the phycobilisome, to the chlorophyll-containing core-complexes in the photosynthetic membrane. Genes coding for the apoprotein, ApcE, from Nostoc sp. PCC 7120 and for a C-terminally truncated fragment ApcE(1-240) containing the chromophore binding cysteine-195 were overexpressed in Escherichia coli. Both bind covalently phycocyanobilin (PCB) in an autocatalytic reaction, in the presence of 4M urea necessary to solubilize the proteins. If judged from the intense, red-shifted absorption and fluorescence, both products have the features of the native core-membrane linker LCM, demonstrating that the lyase function, the dimerization motif, and the capacity to extremely red-shift the chromophore are all contained in the N-terminal phycobilin domain of ApcE. The red-shift is, however, not the result of excitonic interactions: Although the chromoprotein dimerizes, the circular dichroism shows no indication of excitonic coupling. The lack of homologies with the autocatalytically chromophorylating phytochromes, as well as with the heterodimeric cysteine-alpha84 lyases, indicates that ApcE constitutes a third type of bilin:biliprotein lyase.

Apoproteins↗

Lys691 and Asp714 of the Na+/K+-ATPase alpha subunit are essential for phosphorylation, dephosphorylation, and enzyme turnover.

P-type ATPases such as the sodium pump appear to be members of a superfamily of hydrolases structurally typified by the L-2-haloacid dehalogenases. In the dehalogenase L-DEX-ps, Lys151 serves to stabilize the excess negative charge in the substrate/reaction intermediates and Asp180 coordinates a water molecule that is directly involved in ester intermediate hydrolysis. To investigate the importance of the corresponding Lys691 and Asp714 of the sodium pump alpha subunit, sodium pump mutants were expressed in yeast and analyzed for their properties. Lys691Ala, Lys691Asp, Asp714Ala, and Asp714Arg mutants were inactive, not only with respect to ATPase activity but also to interaction with the highly sodium pump-specific inhibitors ouabain or palytoxin (PTX). In contrast, conservative mutants Lys691Arg and Asp714Glu retained some of the partial activities of the wild-type enzyme, although they completely failed to display any ATPase activity. Yeast cells expressing Lys691Arg and Asp714Glu mutants are sensitive to the sodium pump-specific inhibitor PTX and lose intracellular K+. Their sensitivity to PTX, with EC50 values of 118 +/- 24 and 76.5 +/- 3.6 nM, respectively, was clearly reduced by almost 7- or 4-fold below that of the native sodium pump (17.8 +/- 2.7 nM). Ouabain was recognized under these conditions with low affinity by the mutants and inhibited the PTX-induced K+ efflux from the yeast cells. The EC50 for the ouabain effect was 183 +/- 20 microM for Lys691Arg and 2.3 +/- 0.08 mM for the Asp714Glu mutant. The corresponding value obtained with cells expressing the native sodium pump was 69 +/- 18 microM. In the presence of Pi and Mg2+, none of the mutant sodium pumps were able to bind ouabain. When Mg2+ was omitted, however, both Lys691Asp and Asp714Glu mutants displayed ouabain binding that was reduced by Mg2+ with an EC50 of 0.76 +/- 0.11 and 2.3 +/- 0.2 mM, respectively. In the absence of Mg2+, ouabain binding was also reduced by K+. The EC50 values were 1.33 +/- 0.23 mM for the wild-type enzyme, 0.93 +/- 0.2 mM for the Lys691Arg mutant, and 1.02 +/- 0.24 mM for the Asp714Glu enzyme. None of the neutral or nonconservative mutants displayed any ouabain-sensitive ATPase activity. Ouabain-sensitive phosphatase activity, however, was present in membranes containing either the wild-type (1105 +/- 100 micromol of p-nitrophenol phosphate hydrolyzed min(-1) mg of protein(-1)) or the Asp714Glu mutant (575 +/- 75 micromol min(-1) mg(-1)) sodium pump. Some phosphatase activity was also associated with the Lys691Arg mutant (195 +/- 63 micromol min(-1) mg(-1)). The results are consistent with Lys691 and Asp714 being essential for the phosphorylation/dephosphorylation process that allows the sodium pump to accomplish the catalytic cycle.

Acrylamides↗

[A case-control study on the polymorphisms of methylenetetrahydrofolate reductase 1298A-->C and susceptibility of esophageal cancer].

OBJECTIVE: To investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC). METHODS: We conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction. RESULTS: (1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC. CONCLUSION: Results in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.

Adult↗

[Biomass distribution patterns of Alnus hirsuta and Betula platyphylla-swamp ecotone communities in Changbai Mountains].

In order to reveal the growth patterns of dominant tree species and the distribution patterns of community biomass along the horizontal environmental gradients or among the vertical layers of communities in Changbai Mountains, this paper studied the biomass distribution patterns of Alnus hirsuta-swamp and Betula platyphylla-swamp ecotone communities. The results showed that there were some differences in growth rate and in adaptability to habitats between A. hirsuta and B. platyphylla. In the wetland habitats of the ecotone, A. hirsuta grew 1-2 times faster than B. platyphylla, but along the gradient from swamp to forest, it grew slowly, while B. platyphylla grew fast. Therefore, A. hirsuta was a favorite tree species in wetland habitats. The distribution pattern of organ biomass was similar between A. hirsute and B. platyphylla, the trunk being 1/2, tree root 1/4, branch 1/10, bark 1.5/20, and leaf 1/20. The vertical distribution pattern of biomass was also similar between A. hirsute-swamp and B. platyphylla-swamp ecotone communities, the tree, shrub, and herbage layer accounted for 87%-90%, 7%-9%, and 2%-3%, respectively in the whole ecotone communities. The community biomass increased linearly from swamp to forest with the change of environment factors.

Alnus↗

Direct immunoassay of estrone by capillary electrophoresis with laser-induced fluorescence detection.

An immunoassay for estrone (E(1)) in women's serum, based on the competitive reaction between fluorescein-labeled complete antigen and E(1) with limited amount of anti-estrone monoclonal antibody is described. A thermally reversible hydrogel, poly-N-isopropylacrylamide (pNIPA), was added to the buffer to improve the reproducibility. With a laser-induced fluorescence (LIF) detector, the capillary electrophoretic immunoassay (CEIA) can be applied to determine E(1) at a concentration lower than 19.6 pg/mL. The E(1) levels in ten normal women's serum were measured at the range of 118.6-222.0 pg/mL.

Acrylic Resins↗

A potential food-grade cloning vector for Streptococcus thermophilus that uses cadmium resistance as the selectable marker.

A potential food-grade cloning vector, pND919, was constructed and transformed into S. thermophilus ST3-1, a plasmid-free strain. The vector contains DNAs from two different food-approved organisms, Streptococcus thermophilus and Lactococcus lactis. The 5.0-kb pND919 is a derivative of the cloning vector pND918 (9.3 kb) and was constructed by deletion of the 4.3-kb region of pND918 which contained DNA from non-food-approved organisms. pND919 carries a heterologous native cadmium resistance selectable marker from L. lactis M71 and expresses the Cd(r) phenotype in S. thermophilus transformants. With the S. thermophilus replicon derived from the shuttle vector pND913, pND919 is able to replicate in the two S. thermophilus industrial strains tested, ST3-1 and ST4-1. Its relatively high retention rate in S. thermophilus further indicates its usefulness as a potential food-grade cloning vector. To our knowledge, this is the first report of a replicative potential food-grade vector for the industrially important organism S. thermophilus.

Cadmium↗

[Interactions between lifestyle, methylanetetrahydrofolate reductase gene and polymorphisms in thymidylate synthase gene with risk of stomach cancer].

OBJECTIVE: To evaluate interactions between lifestyle, methylanetetrahydrofolate reductase gene (MTHFR) and polymorphisms in the 3'-untranslated region (3'-UTR) of the thymidylate synthase gene (TS) with reference to development of stomach cancer (SC). METHODS: We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. TS genotypes were identified by polymerase chain reaction. RESULTS: (1) The frequencies of TS genotypes (+6 bp/+6 bp, +6 bp/-6 bp and -6 bp/-6 bp) among the cases were 5.6%, 47.7% and 46.7% and among the controls were 9.0%, 54.0% and 37.0%, respectively. Individuals identified as -6 bp/-6 bp genotype had a slightly higher risk for SC than those individuals with +6 bp alleles (the crude OR = 1.49, 95% CI: 0.90 - 2.47; adjusted OR = 1.36, 95% CI: 1.00 - 1.78, P = 0.047). (2) Individuals having TS -6 bp/-6 bp genotype and having smoking habit were at a significantly higher risk of developing SC (adjusted OR = 2.79, 95% CI: 1.51 - 5.18) compared with those who had +6 bp alleles with no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing SC (adjusted OR = 1.76, 95% CI: 1.07 - 2.90) compared with those with +6 bp alleles and low consumption of alcohol. As compared with individuals with +6 bp alleles and who had habit of tea drinking, individuals who had TS -6 bp/-6 bp genotype and but without habit of tea drinking had an increased risk of developing SC (adjusted OR = 2.34, 95% CI: 1.43 - 3.82). (3) Individuals with TS -6 bp/-6 bp genotype and with MTHFR T alleles had an increased risk of developing SC (adjusted OR = 2.67, 95% CI: 1.07 - 6.70) compared with those with +6 bp alleles and with MTHRF C/C genotype. CONCLUSION: Results in the present study suggested that there was a combined effect between lifestyle, MTHFR C/T or T/T genotype and TS -6 bp/-6 bp genotype in the development of SC.

Alcohol Drinking↗

Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province, China.

To evaluate interactions between lifestyle factors and glutathione-S-transferases M1 (GSTM1) and GSTT1 genotypes with reference to development of esophageal and stomach cancers, we conducted a case-control study of 141 cases of esophageal cancer, 153 cases of stomach cancer and 223 population-based controls in Huaian City of Jiangsu Province, China. GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction. The GSTM1 null genotype was associated with an increased odds ratio for esophageal cancer (2.17, 95% confidence interval=1.35-3.50), but not for stomach cancer. A combined effect was also observed between smoking and the GSTM1 null genotype with regard to esophageal risk. Tea drinking was a protective factor for both cancers, its effect being independent of the GSTT1 and GSTM1 genotypes. These findings suggest the GSTM1 polymorphism is involved in the susceptibility to esophageal cancer development, and tea consumption reduces the risk of esophageal and stomach cancers.

Adult↗

Cloning vectors for Streptococcus thermophilus derived from a native plasmid.

A 3.5-kb native plasmid (pND103) was identified in Streptococcus thermophilus ST2-1. Preliminary sequence analysis indicated that pND103 belongs to group I S. thermophilus plasmids. A region of approximately 2 kb appears to contain three components: a plus origin of replication (ori) typical of plasmids that replicate via rolling circle replication; a gene encoding a replication protein (rep); and a gene encoding a small heat shock protein (hsp). pND103 was then used to construct S. thermophilus/Escherichia coli hybrid cloning vectors by ligating different portions of pND103 to an origin-probe vector (pND330) composed of pUC19 and a Gram-positive erythromycin resistance gene. The shuttle vectors (pND913, pND914 and pND915) were successfully introduced back into plasmid-free S. thermophilus ST3-1 as well as to Lactococcus lactis LM0230 and E. coli JM109. Segregational and structural stability study indicated that these vectors can be maintained in these hosts. The results indicated that pND913, pND914 and pND915 are potential shuttle cloning vectors for S. thermophilus.

Base Sequence↗

High-performance liquid chromatographic determination of 2-hydroxypropyl-gamma-cyclodextrin in different biological fluids based on cyclodextrin enhanced fluorescence.

A high-performance size exclusion chromatographic method with analyte enhanced fluorescence detection is described for the analysis of 2-hydroxypropyl-gamma-cyclodextrin (HPGCD) in different biological fluids. The principle of detection was the in situ complexation of 8-anilinonaphthalene-1-sulfonic acid (ANS) by HPGCD. When HPGCD eluted from the column the increased fluorescence was measured at excitation and emission wavelengths of 270 and 512 nm, respectively. Solid-phase extraction cleanup and concentration of samples resulted in higher than 78% recovery of HPGCD for each of the studied biological fluids. Some important details of the method development as well as the validation of the method for rabbit plasma, rabbit aqueous humour, monkey plasma and monkey urine are given. The limits of quantification varied between 1 and 10 nmol/ml (correspond to 1.5-15 microg/ml) depending on the biological matrix used. The method was successfully adapted in another laboratory proving that HPGCD had not absorbed into aqueous humour and plasma after topical application of HPGCD containing eye drop in rabbits.

2-Hydroxypropyl-beta-cyclodextrin↗

A distinct physiological state of Lactococcus lactis cells that confers survival against a direct and prolonged exposure to severe stresses.

When exponential phase cultures of Lactococcus lactis were directly exposed to severe stresses (acid, bile salt, heat, and hydrogen peroxide) for a prolonged period, most of the cells were quickly killed, however, a small number of the cells, approximately 0.01% of the population, was found to survive. How these 'survivor' cells might have survived the stresses, when other supposedly-the-same cells could not, was investigated. The cultures were not exposed to any mild stresses prior to the exposure to the severe stresses, and therefore adaptation can be ruled out as the cause of survival. When the survivor cells were re-cultured and re-exposed to the same severe stresses a similar pattern of survival was displayed, indicating that the survivor cells were not stress-resistant mutants. Furthermore, the survivor cells displayed typical growth kinetics once they were freed of the stresses. The survivor cells appear to be in a distinct physiological state, because when they were tested against a second stress they exhibited significantly greater survival against that stress than the normal cells exposed to the same stress. Also, cells at different time points of synchronously growing culture displayed different levels of survival against stress. It is proposed that the difference in survival of exponential phase cells is due to the difference in the protein makeup of cells at different stages of the cell cycle.

Acids↗

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid omega-hydroxylase activity.

The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 +/- 3.2 mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.

Animals↗

[Polymorphisms of methylenetetrahydrofolate reductase C677T and the risk of stomach cancer].

OBJECTIVE: In order to study the relation between polymorphisms of methylenetetrahydrofolate reductase C677T (MTHFR) and susceptibility of stomach cancer (SC). METHODS: We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were detected by PCR-RFLP method. RESULTS: (1) The frequency of MTHFR variant genotypes (C/T + T/T) among the cases (79.4%) was significantly higher than the controls (68.5%) (P = 0.041 6); the crude OR for SC was 1.78 (95% CI: 0.99 - 3.22). After adjustment for sex and age, the OR for SC was 1.89 (95% CI: 1.08 - 3.32). (2) Subjects who had MTHFR variant genotypes and having smoking habit were at a significantly higher risk of developing SC (OR = 7.72, 95% CI: 2.23 - 26.79) compared with those who had wild-type homozygotes (C/C) genotype and no smoking habit. Individuals who had variant genotypes and who had habit of frequent alcohol drinking were at an increased risk of developing SC (OR = 3.08, 95% CI: 1.30 - 7.23) compared with those with C/C genotype and low consumption of alcohol. As compared with subjects with C/C genotype and low consumption of alcohol and no smoking habit, individuals who had variant genotypes and who had habits of frequent alcohol drinking and smoking had 12.96 (95% CI: 2.76 - 70.46) folds risk developing SC. CONCLUSIONS: These results in the present study suggested that the polymorphisms of MTHFR C677T was associated with risk of developing SC, and there was a coordinated effect between MTHFR genotypes and habits of smoking and alcohol drinking in the development of SC.

Alcohol Drinking↗

Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking.

Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.

Adult↗