Search PubMed⌕ Search

Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 505 records · Page 28Linked to original sources
PubMed1999

Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy.

Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines. A total of 2,407 lamotrigine plasma concentrations from 527 patients with epilepsy were analyzed. Regression equations for oral clearance were developed as a function of body size, age (18-64 years), gender, race, and use of concomitant antiepileptic drugs. The population mean apparent oral clearance of lamotrigine in adult patients receiving one concomitant enzyme-inducing antiepileptic drug and not valproic acid was estimated to be 1 mL/min/kg. Gender and age did not affect clearance significantly. On average, clearance was reduced by 25% in non-whites and increased by 13% in patients receiving more than one concomitant enzyme-inducing antiepileptic agent. Lamotrigine did not influence the disposition of phenytoin or carbamazepine. Dosing adjustments for lamotrigine in patients receiving concomitant enzyme-inducing antiepileptic drugs and not valproic acid should not be necessary for age, gender, or the number of concomitant enzyme-inducing antiepileptic drugs. Lamotrigine does not influence the dosing requirements for phenytoin or carbamazepine.

Adolescent↗
PubMed1999

A simulation study of confounding in generalized linear models for air pollution epidemiology.

Confounding between the model covariates and causal variables (which may or may not be included as model covariates) is a well-known problem in regression models used in air pollution epidemiology. This problem is usually acknowledged but hardly ever investigated, especially in the context of generalized linear models. Using synthetic data sets, the present study shows how model overfit, underfit, and misfit in the presence of correlated causal variables in a Poisson regression model affect the estimated coefficients of the covariates and their confidence levels. The study also shows how this effect changes with the ranges of the covariates and the sample size. There is qualitative agreement between these study results and the corresponding expressions in the large-sample limit for the ordinary linear models. Confounding of covariates in an overfitted model (with covariates encompassing more than just the causal variables) does not bias the estimated coefficients but reduces their significance. The effect of model underfit (with some causal variables excluded as covariates) or misfit (with covariates encompassing only noncausal variables), on the other hand, leads to not only erroneous estimated coefficients, but a misguided confidence, represented by large t-values, that the estimated coefficients are significant. The results of this study indicate that models which use only one or two air quality variables, such as particulate matter [less than and equal to] 10 microm and sulfur dioxide, are probably unreliable, and that models containing several correlated and toxic or potentially toxic air quality variables should also be investigated in order to minimize the situation of model underfit or misfit.

Air Pollution↗
PubMed1999

Ovariectomized murine model of postmenopausal calcium malabsorption.

Two experiments were carried out to examine whether the ovariectomized mouse is a potential in vivo model of intestinal calcium malabsorption as occurs in postmenopausal osteoporosis. In the first experiment, we compared the effects of ovariectomy and 17 beta-estradiol (E2) therapy on calcium absorption in C3H/HeJ (C3H) and C57BL/6J (C57BL) mice, which have high and low peak bone mass, respectively. For each strain of mice, three groups were studied: sham operated, ovariectomized, (OVX), and OVX + E2 (60 micrograms/kg of body weight [bw]/day). Therapy was continued for 35 days and calcium absorption measured. In the C3H mice, ovariectomy caused an increase in fecal calcium (17.6%), and a decrease in the amount (12.8%) and percentage (12.5%) of calcium absorbed. The decrease was prevented by E2 therapy, but the differences in the calcium absorption parameters among the groups were not statistically significant. In contrast, in the C57BL mice, ovariectomy caused a marked increase in fecal calcium (84.5%, p < 0.01), and a marked decrease in the amount (55%, p < 0.01) and percentage (34.8%, p < 0.001) of calcium absorbed, and the decrease in the percentage of calcium absorbed was partially prevented by E2 therapy (p < 0.05). In experiment 2, a dose-response study of the effects of E2 therapy on calcium absorption in OVX C57BL mice was carried out. Five groups of mice were studied: Group 1, sham operated; Group 2, OVX; Group 3, OVX + 60 micrograms of E2/kg of bw/day; Group 4, OVX + 120 micrograms of E2/kg of bw/day; Group 5, OVX + 240 micrograms of E2/kg of bw/day. Therapy was continued for 28 days and calcium absorption measured. Ovariectomy caused a marked increase in fecal calcium (50%, p < 0.0001) and urinary calcium (31%, p < 0.0001) and a marked decrease in calcium absorption (44.9%, p < 0.0001), and these changes were prevented by E2 therapy. The highest level of calcium absorption (109%, p < 0.0001, vs. OVX) was observed in the 120 micrograms of E2 group. Ovariectomy and E2 slightly increased plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels but there was no significant correlation between 1,25(OH)2D levels and calcium absorption. The findings in the C57BL mice suggest that estrogen is a physiological regulator of calcium absorption in this strain of mice. Furthermore, these findings share many characteristics with intestinal calcium malabsorption and its reversal by estrogen therapy in hypoestrogenic women. We propose that the OVX C57BL mice warrants further characterization as a potential animal model for investigating issues related to calcium malabsorption in postmenopausal women.

Animals↗
PubMed1999

Pharmacokinetics of lamotrigine in children in the absence of other antiepileptic drugs.

We evaluated the pharmacokinetics of lamotrigine in 12 children with epilepsy who were receiving no other antiepileptic drugs. Each patient received a single oral dose of lamotrigine 2 mg/kg. Plasma concentrations of the drug were measured up to 48 hours after dosing. Pharmacokinetic parameters were calculated using noncompartmental methods. After rapid absorption, the lamotrigine concentration declined monoexponentially. Oral clearance was 0.64 +/- 0.26 ml/min/kg. The apparent volume of distribution was 1.50 +/- 0.51 L/kg. Weight-normalized clearance and volume were higher in children than in adults. The mean half-life was 32 hours, similar to that in adults. Should similar plasma lamotrigine concentrations in adults and children be desirable, children will likely require higher weight-normalized doses at the same dosing frequency.

Anticonvulsants↗
PubMed1999

Relationship between herpesviruses and adult periodontitis and periodontopathic bacteria.

BACKGROUND: Various mammalian viruses and specific bacteria seem to play important roles in the pathogenesis of human periodontitis. This study examined the relationship between subgingival herpesviruses and periodontal disease and potential periodontopathic bacteria in 140 adults exhibiting either periodontitis or gingivitis. METHODS: A nested-polymerase chain reaction (PCR) method determined the presence of Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), human cytomegalovirus (HCMV), and herpes simplex virus (HSV) and a 16S rRNA PCR detection method identified Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola. RESULTS: Using a logistic analysis, EBV-1 showed significant positive association with P. gingivalis (odds ratio [OR] 3.37), and with coinfections of P. gingivalis and P. intermedia (OR 4.03); P. gingivalis and B. forsythus (OR 3.84); P. gingivalis and T. denticola (OR 4.17); P. gingivalis, B. forsythus, and T. denticola (OR 4.06); and P. gingivalis, P. nigrescens, and T. denticola (OR 3.29). EBV-1 also showed positive association with severe periodontitis (OR 5.09), with increasing age (OR 1.03), and with periodontal probing depth at the sample sites (OR 1.77). HCMV was positively associated with coinfections of P. gingivalis and P. nigrescens (OR 3.23); P. gingivalis, B. forsythus, and P. nigrescens (OR 3.23); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.59); with severe periodontitis (OR 4.65); and with age (OR 1.03). Patients with mixed viral infections revealed significant associations with P. gingivalis (OR 2.27), and with coinfections of P. gingivalis and B. forsythus (OR 2.06); P. gingivalis and P. nigrescens (OR 2.91); P. gingivalis, B. forsythus, and P. nigrescens (OR 2.91); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.70) with the clinical diagnosis of slight (OR 3.73), moderate (OR 3.82), or severe periodontitis (OR 4.36), and with probing depth at the sample sites (OR 1.39). HSV and EBV-2 showed no significant associations with any of the variables tested. CONCLUSIONS: The results indicate that subgingival EBV-1, HCMV, and viral coinfections are associated with the subgingival presence of some periodontal pathogens and periodontitis. Herpesviruses may exert periodontopathic potential by decreasing the host resistance against subgingival colonization and multiplication of periodontal pathogens.

Actinobacillus Infections↗
PubMed1999

Arsenic trioxide induces apoptosis of oesophageal carcinoma in vitro.

The arsenic compounds in traditional Chinese medicine have been recorded to have therapeutic effects on the treatment of psoriasis, syphilis, rheumatosis and a number of malignant tumours. Recent studies showed that arsenic trioxide can induce clinical remission in patients with acute promyelocytic leukemia, including those who have relapsed after retinoic acid treatment. however, the mechanism of how arsenic trioxide targets tumour cells is not clearly understood. We have examined the effects of arsenic trioxide on oesophageal carcinoma cell line EC8712. Our results demonstrated that the growth and survival of tumour cells were markedly inhibited by arsenic trioxide. The half dose effect (ED50) was at the concentration of 1 microM. Electron microscopic study demonstrated that EC8712 tumour cells treated with arsenic trioxide display a typical morphological appearance of apoptosis, including chromatin condensation and fragmentation of the nuclei. In contrast, no apoptotic features were observed in tumour cells without arsenic trioxide treatment. TUNEL assay also showed the biological features of apoptosis in cells treated with arsenic trioxide. Flow cytometry analyses showed that apoptotic peak was identified in arsenic trioxide treated cells but not in the control. Apoptotic cells in arsenic trioxide treated group account for 35% of total cell populations after three days treatment at a dose of 3 microM. In short, our results suggested that the anticancer effect of arsenic trioxide is due, at least in part, to the induction of apoptosis in cancer cells.

Antineoplastic Agents↗
PubMed1999

Intracranial acute arterial ischemia of the anterior circulation: evaluation with three-dimensional time-of-flight magnetic resonance angiography.

BACKGROUND: Stroke has been the second most common cause of death, after cancer, in Taiwan since 1983. The cost of stroke to society in terms of morbidity, mortality and economics is profound. Heightened interest in the early diagnosis and treatment of acute stroke challenges neuroimagers to optimize available modalities and to develop new techniques for the evaluation of cerebrovascular disease. The aim of this study was to investigate the effectiveness of magnetic resonance angiography (MRA) in conjunction with spin-echo imaging in patients with acute brain infarction of the anterior circulation. METHODS: Magnetic resonance imaging and three-dimensional Fourier transformed time-of-flight MRA studies, performed on 50 patients within one week after the onset of cerebral ischemia, were retrospectively reviewed and correlated with clinical records. Five of the 50 MRAs were considered nondiagnostic and excluded because of poor patient cooperation. RESULTS: In 41 of the 45 cases, the area of infarct corresponding to the clinical deficit at the time of study was identified on T2-weighted spin-echo images. Arterial occlusions or severe stenoses that corresponded to ischemic manifestations were identified with MRA in 37 of the 45 patients. A focal discontinuity with decreased arterial caliber corresponded to stenosis and nonvisualization of distal branches represented arterial occlusion. MRA provided information for 23 cases not obtained from the MR images. CONCLUSIONS: Vascular lesions demonstrated on intracranial MRA show a high correlation with infarct distribution. MRA, which provides information adjunctive to conventional MR imaging in a majority of cases, is concluded to be an important component of the complete evaluation of brain infarction.

Acute Disease↗
PubMed1999

CYP2D6 genotype and the incidence of anal and vulvar cancer.

The risks of anal and vulvar cancer are strongly related to cigarette smoking. Smokers are exposed to a substantial quantity of tobacco-specific nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK is present in the mucus of the female genital tract. The enzyme debrisoquine 4-hydroxylase (CYP2D6) activates NNK and is present in foreskin kerotinocytes and cervical epithelial cells. A polymorphism for the gene CYP2D6 exists, and persons who possess alleles that are associated with reduced levels of CYP2D6 activity might be expected to be at a relatively lower risk of cancers arising from NNK exposure. To test this hypothesis, we conducted a case-control study to examine the association of CYP2D6 genotype and the incidence of anal and vulvar cancer among cigarette smokers in western Washington State. We tested for 14 alleles (*1-*12, *14, and *17) among cases (25 men and 43 women with anal cancer, 64 women with vulvar cancer) and controls (30 men and 110 women). Contrary to the hypothesis, cases were not less likely than controls to have one (43.9 versus 40.7%) or two (6.8 versus 4.3%) inactivating alleles (*3, *4, *5, *6, *7, *8, *11, or *12). There was a suggestion that, if anything, the combined anal and vulvar cancer risk increased (rather than decreased) with an increasing number of CYP2D6 inactivation alleles: odds ratio = 1.2, 95% confidence interval = 0.7-2.0 with one inactivating allele; odds ratio = 1.8, 95% confidence interval = 0.6-5.4 with two inactivating alleles. These results provide no support for the hypothesis that cigarette smokers who carry the CYP2D6 alleles that result in a low activity phenotype have a decreased risk of anogenital cancer.

Adolescent↗
PubMed1999

[Isolating candidate inserted fragment from positive fused phage clones using quantitative PCR].

OBJECTIVE: To isolate quickly and exactly the specific inserted fragment from fused phage clones which were obtained from cDNA library by hybridization. METHODS: According to the amplification principle of quantitative polymerase chain reaction (PCR) and based on the difference of original template quantity,target cDNA fragment was isolated and identified by two PCRs. RESULTS: A positive clone with specific cDNA fragment of HumGT-H1 gene was obtained from a two-phage fused clone by using this method,and the inserted fragment was verified to be the 5' cDNA sequence of HumGT-H1,1.9kb in length. So another hybridization screening is not necessary. CONCLUSION: The method presented is effective and rapid in gene cloning and can greatly save time and materials.

Bacteriophages↗
PubMed1999

Glutathione S-transferase M1 and susceptibility to nasopharyngeal carcinoma.

Genetic polymorphisms for enzymes that metabolize tobacco smoke have been reported to determine susceptibility to several smoking-related cancers, including cancers of the lung, bladder, and head and neck. Glutathione S-transferase M1 (GSTM1) detoxifies benzo(a)pyrene and other carcinogens in tobacco smoke. Approximately 50% of Caucasians lack the GSTM1 gene. Because the most common type of nasopharyngeal cancer (NPC), squamous cell carcinoma, is related to smoking, we sought to determine whether GSTM1 is associated with risk for NPC. Cases (n = 83) were from a population-based study conducted from 1987 to 1993 at five cancer registries in the United States. Random-digit dialing controls (n = 114) were matched to the cases for age, sex, and registry. Subjects participated in a phone interview and blood draw. Absence of GSTM1 was associated with increased risk for NPC (odds ratio = 1.9, 95% confidence interval = 1.0-3.3 for all cases; and odds ratio = 1.7, 95% confidence interval = 0.8-3.5 for squamous cell cases). This relationship was not modified by smoking history, but stronger relationships between glutathione S-transferase and NPC were suggested among subjects who used alcohol more frequently than others, older subjects (50 or more years of age), and women relative to men. These data indicate that absence of GSTM1 moderately increases risk for NPC and add to growing evidence that GSTM1 is a determinant of risk for several smoking-related cancers.

Adolescent↗
PubMed1999

Intraperitoneal addition of hyaluronan improves peritoneal dialysis efficiency.

BACKGROUND: It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. METHODS: A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. RESULTS: Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. CONCLUSIONS: (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

Absorption↗
PubMed1999

Identification of a novel intron and 4 polymorphisms in the gene encoding the gamma subunit of the epithelial sodium channel.

The amiloride-sensitive epithelial sodium channel is a highly selective sodium channel that constitutes the rate-limiting step of sodium reabsorption in distal nephrons. It consists of at least 3 subunits (alpha, beta, and gamma) of similar structure and plays an important role in sodium and fluid homeostasis. Defects of this channel have been critically implicated in Liddle syndrome (pseudoaldosteronism) and pseudohypo-aldosteronism type 1. A sample of 48 individuals from 23 nuclear families was selected from Anhui, China. We sequenced 12 exons and flanking intronic sequences and discovered a new 207-bp intron located in the previously described exon X of Thomas et al. (1996). In addition, 4 novel single nucleotide polymorphisms were identified; 3 were in exon 3 and 1 was in exon 13. Furthermore, 2 base substitutions in exon 13 were present in all the Chinese subjects compared with the published European SCNN1G DNA sequence.

Base Sequence↗
PubMed1999

Detection and assessment of circle of Willis aneurysms in acute subarachnoid hemorrhage with three-dimensional computed tomographic angiography: correlation with digital substraction angiography findings.

In this retrospective study, we examined the usefulness of computed tomographic angiography (CTA) for the detection and assessment of circle of Willis aneurysms in patients with acute nontraumatic subarachnoid hemorrhage (SAH), using selective digital substraction angiography (DSA) as the gold standard. Thirty-five patients who presented with acute, nontraumatic SAH, diagnosed on the basis of unenhanced computed tomography or lumbar puncture findings or both, underwent both CTA and DSA. The CTA images were interpreted for the presence, location, size, and shape of the aneurysm, presence of a neck, and relationship of the aneurysm to adjacent arterial branches. The CTA and DSA images were then compared, with the latter images serving as the gold standard. DSA revealed 37 aneurysms in 32 patients and ruled out intracranial aneurysms in the remaining three. The sensitivity and specificity of CTA for aneurysm detection were 97% and 100%, respectively. The size of the smallest aneurysm shown was 4 mm, and the largest aneurysm was 21 mm. The size and lobularity of the aneurysms estimated from CTA images corresponded well with those estimated from DSA images. In addition, CTA provided a three-dimensional representation of the aneurysmal lesion, which was considered useful for surgical planning. Our results confirm the accuracy of CTA in comparison with DSA. Because of its reliability, minimal invasiveness, and rapidity, CTA may become the technique of choice for neuroradiologic work-up of SAH patients. DSA then would be used to diagnose intracranial aneurysms only in selected, questionable cases.

Acute Disease↗
PubMed1999

N-acetylglucosaminyltransferase V activity in metastatic models of human hepatocellular carcinoma in nude mice.

N-linked beta 1-6 branched oligosaccharides may contribute directly to the malignant phenotype including metastatic potential of tumour cells. Increased beta 1-6 branching was associated with an increased level of N-acetylglucosaminyltransferase V (GnT V). In this report, the tissues from two metastatic models of human hepatocellular carcinoma (HCC) in nude mice were obtained. GnT V activity and mRNA level were determined. Results showed that GnT V activity in highly metastatic LCI-D20 models (Liver Cancer Institute, passage time: 20 days) (413.1+/-86.4U) was much higher than that in low metastatic LCI-D35 model (passage time 35 days) (155.3+/-31.9U). Northern blot showed that the mRNA level of GnT V in two models had no change. During the selection of a highly metastatic LCI-D20 model, GnT V activity increased from 301.6+/-57.3U to 413.1+/-86.4U while the highly metastatic LCI-D20 model acquired higher metastatic ability after selection. When highly metastatic LCI-D20 model tissues were implanted subcutaneously (s.c.), the GnT V activity decreased dramatically from 413.1+/-86.4U to 94.9U. This is the first report that GnT V activity increased in HCC during metastasis in vivo.

Animals↗
PubMed1999

Decreased in vitro formation of AGEs with extraneal solution compared to dextrose-containing peritoneal dialysis solutions.

Extraneal peritoneal dialysis (PD) solution (Baxter Healthcare, Deerfield, Illinois, U.S.A.) contains glucose polymer (icodextrin) as an osmotic agent in place of dextrose. We investigated the ability of Extraneal to form advanced glycation end products (AGEs) in vitro compared to standard PD solutions containing dextrose. Extraneal, Dianeal PD-2 [1.5%, 2.5%, or 4.25% dextrose (Baxter Healthcare)], or phosphate buffered saline (PBS) were incubated for 45 days with human serum albumin (HSA) or type IV collagen. AGE formation was measured by spectrofluorometry using excitation at 350 nm and emission at 430 nm. Solutions were also incubated with collagen affixed to plastic, simulating matrix collagen in the peritoneal membrane. In addition, AGE formation was assessed using icodextrin metabolites (maltose, maltotriose, and maltotetraose) at concentrations normally found in the plasma of patients treated using icodextrin. For PD solutions incubated with albumin, the relative order of AGE formation was: 4.25% dextrose > 2.5% dextrose > 1.5% dextrose > Extraneal. For incubations with collagen (in solution or affixed to plastic), AGE formation was greatest for 4.25% dextrose, intermediate for Extraneal and 2.5% dextrose, and lowest for 1.5% dextrose. Incubation of icodextrin metabolites with albumin for 45 days did not result in appreciable AGE formation. These results confirm that solutions containing icodextrin result in less in vitro AGE formation than do high dextrose solutions. The results also suggest that Extraneal may lead to improved solution biocompatibility in vivo.

Glucans↗
PubMed1999

Airway obstruction in general anesthesia--two different episodes in the same patient: case report.

The case of a patient with Apert's syndrome (acrocephalosyndactyly) who had a tracheostomy tube and who encountered two different episodes of critical airway obstruction during two different general-anesthetic procedures for craniofacial surgery is reported. The first episode, at the age of four, involved occlusion of the uncuffed tracheostomy tube by a blood clot, which might have come from the surgical field of the maxillary Le-Fort III advancement procedure. The second episode was encountered during his emergence from the general anesthesia of a degloving midface osteoplasty and a maxillary Le-Fort I osteotomy procedure 3 years later. Although a cuffed armored tube had been inserted through the tracheostoma to prevent aspiration of blood from the surgical field, the armored tube was plugged by a piece of granulation tissue that might have been dislodged from the peri-stomal area. Factors that lead to tracheostomy tube obstruction, their clinical features and preventive measures are discussed. We believe that being alert to changes in the airway pressure, the ventilation pattern, and the hemodynamic status is necessary during the administration of general anesthesia. Precautions should be taken at all times, particularly for patients with a tracheostomy.

Airway Obstruction↗
PubMed1999

Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction?

5,10-Methylene-tetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, may play a role in the etiology of colorectal adenomas via effects on DNA methylation and nucleotide synthesis. We investigated the association between a common polymorphism (C677T, reduced MTHFR activity) and colorectal adenomas within the Minnesota CPRU case-control study. Cases (n = 527) were diagnosed with colonoscopically confirmed adenomas; controls (n = 645) were derived from the same gastroenterology practice and were polyp free at colonoscopy. Dietary intakes were obtained from a self-administered food-frequency questionnaire prior to colonoscopy. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals for the MTHFR genotype were 0.9 (0.7-1.2; CT versus CC wild-type) and 0.8 (0.6-1.3; TT versus CC). The associations between dietary intakes of folate, vitamin B12, vitamin B6, or methionine and risk of adenomas showed consistent patterns dependent upon MTHFR genotype. Individuals with the TT genotype and intakes of any of these nutrients in the lowest tertile were at elevated risk for adenomas (about 2-3-fold when compared with TT genotype with high intakes). These trends were more pronounced among individuals over age 60, resulting in a 3-6-fold increase for low intakes of folate, B12, and B6. An increased risk with increasing alcohol consumption was observed only among those with the CC genotype (P-trend = 0.005); among those with the TT genotype, those with moderate alcohol consumption were at lowest risk (P for interaction P = 0.02). In conclusion, nutrients involved in the MTHFR metabolic pathway may modify the relationship between the MTHFR C677T polymorphism and colorectal adenomas. Low intakes of folate, vitamin B12, and vitamin B6 increase risk among those (particularly the elderly) with the MTHFR TT genotype.

Adenoma↗