Biomedical subjects

Sheila A Bingham

Publications and source records attributed to Sheila A Bingham.

64 records · Page 4Linked to original sources

PubMed2003

Plasminogen activator inhibitor-1 gene polymorphism and colorectal cancer risk and prognosis.

Plasminogen activator inhibitor-1 (PAI-1) is a factor in urokinase-type plasminogen activator proteolytic system, which is important for tumour invasion and metastasis. Elevated PAI-1 levels in tumours are associated with poor prognosis. An insertion/deletion (4G/5G) promoter polymorphism in the PAI-1 gene affects activity of its product, the 4G/4G genotype being related to higher transcription levels. We assessed the association between the polymorphism and colorectal cancer risk in 206 cancer patients and 355 healthy controls. The results indicated that the PAI-1 gene polymorphism did not affect colorectal cancer risk. Nevertheless, within the case group, the 4G/4G genotype was associated with more advanced tumours (Dukes' C&D), whereas the 5G/5G homozygocity was associated with the Dukes' A&B tumours. The association with the 4G/4G presence was stronger in patients with proximal colon cancers (odds ratio= 6.02, 95% confidence interval, 1.15-31.54). Our results suggest that PAI-1 genotype may be a useful prognostic marker for colorectal cancer, however further specifically designed studies are needed to assess its value in this respect.

Adenocarcinoma↗

PubMed2003

Quantification of isoflavones and lignans in serum using isotope dilution liquid chromatography/tandem mass spectrometry.

Phytoestrogens (isoflavones and lignans) are receiving increasing attention due to a potential protective effect against a number of complex diseases. However, in order to investigate these associations, it is necessary to accurately quantify the levels of phytoestrogens in foods and biological fluids. We report an assay for three isoflavones (daidzein, genistein, and glycitein), two metabolites of daidzein (O-desmethylangolensin and equol), and two lignans (enterodiol and enterolactone) in human serum using electrospray ionisation liquid chromatography/mass spectrometry (LC/MS) with selective reaction monitoring. A simple, highly automated sample preparation procedure requires only 200 microL of sample and utilises one solid-phase extraction stage. Limits of detection are in the region of 10 pg/mL for all analytes except equol, which had a limit of detection of approximately 100 pg/mL. The method developed is suitable for measuring the concentrations of phytoestrogens in blood samples collected from large epidemiological studies. The results of the analysis of serum samples from 300 men and women living in the UK are reported.

Calibration↗

PubMed2003

Apolipoprotein E gene polymorphism and colorectal cancer: gender-specific modulation of risk and prognosis.

Apolipoprotein E ( ApoE ) gene polymorphism is a major factor in lipid metabolism. It has been suggested that this polymorphism can modulate colorectal tumour risk. We tested this hypothesis for colorectal cancer (CRC). ApoE genotype was determined in 206 patients with CRC and 353 healthy controls from the East Anglia region of the U.K. Compared with individuals possessing the most common epsilon 3/epsilon 3 genotype, those with the epsilon 2/epsilon 3 genotype had an increased risk of colon cancer [odds ratio (OR) = 1.91; 95% confidence interval 1.05-3.45]. However, this association was strongly affected by gender. Separate analysis of male and female subjects revealed a highly significant association in men (OR = 2.71; 95% confidence interval 1.30-5.65), but no association in women (OR = 1.01; 95% confidence interval 0.37-2.77). Likewise, the proportion of male patients with more advanced tumours (Dukes' C&D) was significantly increased among those with the ApoE epsilon 2/epsilon 3 genotype (OR = 4.16; 95% confidence interval 1.36-12.75). No significant effect of the presence of the epsilon 4 allele on CRC risk was found; however, there were no epsilon 4/epsilon 4 homozygotes among patients with proximal colon cancers. The ApoE epsilon 3/epsilon 3 majority genotype appeared to be associated with the lowest risk of CRC. These results suggest that ApoE genotype can influence both CRC risk and prognosis of the existing disease in a gender-dependent manner.

Aged↗

PubMed2003

Urine nitrogen as a biomarker for the validation of dietary protein intake.

When validated for completeness, 24-h urine nitrogen obtained from repeated 24-h urine collections has provided useful insights into the validity of dietary assessments, underreporting behaviors and the structure of measurement errors that are associated with different methods. This is particularly so when nitrogen is combined with another marker in 24-h urine samples, potassium. Although the collection of 24-h urine is a tedious procedure, the method is readily accessible and comparatively inexpensive. Other markers of dietary intake and intermediate risk markers may also be measured in the 24-h urine that is obtained.

Biomarkers↗

PubMed2002

Quantitative analysis using gas chromatography/combustion/isotope ratio mass spectrometry and standard addition of intrinsically labelled standards (SAIL)--application to isoflavones in foods.

We have investigated a novel application of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) for the quantitative analysis of the isoflavones in food matrices. Previous methods have been hampered by the lack of analytical standards to introduce early enough in the extraction procedure to allow compensations for losses at all stages of the procedure. In this work we have produced standard materials that can be added at the initial extraction, by intrinsically labelling soya plants by growing them in an atmosphere enriched in the stable isotope of carbon in CO(2). On analysis these plants were shown to contain phytoestrogens at a high (up to 20%) level of enrichment. The dried plant material has been used to estimate the isoflavone concentrations of a set of spiked flours. For daidzein the methodology was shown to produce results comparable to those achieved by GC/MS techniques. The method was less successful for genistein, possibly due to the greater fragility of this compound under the conditions required for the analysis.

Carbon Isotopes↗

PubMed2002

Differences in N-acetylation genotypes between Caucasians and Black South Africans: implications for cancer prevention.

Polymorphic N-acetyltransferase genes (NAT1 and NAT2) determine rapid or slow acetylation phenotypes, which are believed to affect cancer risk related to environmental exposure. Black South Africans have a unique incidence pattern of environment-related cancers, but genetic characteristics of this population are mostly unknown. In this study, we compared NAT1 and NAT2 allele distributions in 101 Black South Africans and 112 UK Caucasians. Frequencies of the rapid alleles were significantly higher in Black South Africans for both NAT1 and NA72. Putative rapid NAT1 genotypes due to the presence of either NAT1*10 or NAT1*11 were found in 74.3% of Black South Africans (only NAT1*10) and 42.0% of UK Caucasians (P < 0.0001). Similarly, NAT2 analysis showed that the presence of NA12*4, NAT2*12A, NAT2*12B, NA72*12C, and NAT2*13 alleles provided significantly higher (P = 0.0001) frequency of rapid acetylation genotypes among Black South Africans (60.4%) than in the Caucasian group (33.9%). The rapid acetylation genotype in Caucasians usually depended on the NAT2*4 allele presence. The significant differences in N-acetylation genotypes can be among the factors determining a distinctive cancer morbidity and mortality pattern observed in Black South Africans. Both further genetic characterization of different populations and development of preventive strategies adopted for ethnicities with different genetic backgrounds are needed to deal adequately with the emerging health care problems in developing multiethnic societies.

Acetylation↗

PubMed2002

Isolation of exfoliated colonocytes from human stool as a new technique for colonic cytology.

Cell exfoliation in the gut is an important cell renewal mechanism. To approach its investigation we applied a novel immunomagnetic technique for isolation of exfoliated cells from human stool. Exfoliated colonocytes were isolated from 168 stool samples. The cells were assessed microscopically using conventional stains and immunohistochemistry. The technique allowed us to obtain well-preserved colonocytes displaying characteristic features of well-differentiated colonic epithelium and positive immunostaining for cytokeratin 5/8. No mucin-producing cells were found. Exfoliated cells did not produce inducible nitric oxide synthase, albeit cultured colon carcinoma cells HT-29 analysed in parallel showed strong immunostaining. Analysis of exfoliated cell numbers in consecutive stool samples from the same subjects revealed considerable interindividual variation. Overall exfoliated colonocyte numbers were relatively low, isolation being unaffected by addition during the procedure of excessive amounts of HT-29 cells. Apoptosis was extremely rare among exfoliated colonocytes. Well-preserved exfoliated colonocytes can be consistently isolated from human faeces using a simple procedure. Our findings suggest that the actual process of cell exfoliation in the human colon may be much less intense than is generally accepted. Exfoliated cell isolation from human stool constitutes a convenient non-invasive approach that can be used for diagnostic and research purposes.

Colon↗

PubMed2002

Biomarkers in nutritional epidemiology.

OBJECTIVE: To illustrate biomarkers of diet that can be used to validate estimates of dietary intake in the study of gene-environment interactions in complex diseases. DESIGN: Prospective cohort studies, studies of biomarkers where diet is carefully controlled. SETTING: Free-living individuals, volunteers in metabolic suites. SUBJECTS: Male and female human volunteers. RESULTS: Recent studies using biomarkers have demonstrated substantial differences in the extent of measurement error from those derived by comparison with other methods of dietary assessment. The interaction between nutritional and genetic factors has so far largely gone uninvestigated, but can be studied in epidemiological trials that include collections of biological material. Large sample sizes are required to study interactions, and these are made larger in the presence of measurement errors. CONCLUSIONS: Diet is of key importance in affecting the risk of most chronic diseases in man. Nutritional epidemiology provides the only direct approach to the quantification of risks. The introduction of biomarkers to calibrate the measurement error in dietary reports, and as additional measures of exposure, is a significant development in the effort to improve estimates of the magnitude of the contribution of diet in affecting individual disease risk within populations. The extent of measurement error has important implications for correction for regression dilution and for sample size. The collection of biological samples to improve and validate estimates of exposure, enhance the pursuit of scientific hypotheses, and enable gene-nutrient interactions to be studied, should become the routine in nutritional epidemiology.

Biomarkers↗

PubMed2002

Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.

Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M(1)-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M(1)-dG levels and whether M(1)-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoblot blot assay. This study has shown for the first time that M(1)-dG is present in human colorectal tissue. M(1)-dG levels ranged from undetectable (n = 13) to 12.23 per 10(7) total bases. Mean levels were 4.3 +/- 3 and 4.6 +/- 2.9 per 10(7) total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M(1)-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M(1)-dG adducts (P < 0.005).

Adenoma↗

PubMed2001

Mammographic breast density as a biomarker of effects of isoflavones on the female breast.

Isoflavones possess both estrogenic and anti-estrogenic actions, and are hypothesized to protect against breast cancer. However, two intervention studies of markers of proliferation on breast tissue have raised concerns that soy isoflavones may have an estrogenic effect on breast tissue. Increased mammographic breast density is associated with an elevated risk of breast cancer, although the mechanism underlying this relationship has not been explained. Estrogens increase and anti-estrogens decrease breast density. Breast density may therefore serve as a biomarker of estrogenic or anti-estrogenic effects of a treatment on breast tissue. The effect of isoflavones on breast density is under investigation.

Biomarkers↗