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K F Gey

Publications and source records attributed to K F Gey.

At least 19 recordsLinked to original sources

Serum alpha-tocopherol concentration in relation to subsequent colorectal cancer: pooled data from five cohorts.

BACKGROUND: Vitamin E is an antioxidant that inhibits mutagenesis and cell transformation. Previous findings in five prospective epidemiologic studies suggested that the level of serum alpha-tocopherol, the predominant form of vitamin E in the blood, was lower in subjects who subsequently developed colorectal cancer than in control subjects. However, the difference was neither obvious nor statistically significant in any one of these five studies. PURPOSE: To evaluate in greater detail the association between serum alpha-tocopherol concentration and risk of colorectal cancer, we pooled and analyzed the original data from the five studies. Our analyses were designed to (a) test the hypothesis with greater statistical power, (b) examine the association after adjustment for serum cholesterol levels, and (c) evaluate the association after uniform exclusion of cases diagnosed shortly after blood specimens were drawn. METHODS: Data for individual subjects were analyzed. To make the design of the component investigations uniformly nested case-control studies with individual matching, we matched controls to cases in two of the cohorts. Subjects were categorized according to study-specific quartile of serum alpha-tocopherol level within the study. The pooled analysis included 289 cases of colorectal cancer and 1267 matched controls. RESULTS: For cancers of the colon and rectum combined, the matched odds ratio (OR) for the highest quartile of serum alpha-tocopherol concentration compared with the lowest was 0.6 (95% confidence interval [CI] = 0.4-1.0). Adjustment for serum cholesterol level attenuated the OR to 0.7 (95% CI = 0.4-1.1). CONCLUSION: The results suggest that serum alpha-tocopherol concentration may be inversely related to risk of colorectal cancer. It is unclear whether an association exists, however, because the association between serum alpha-tocopherol level and decreased risk of colorectal cancer was modest, the CIs were wide, and, overall, the tests for trend in effect were not significant. IMPLICATIONS: Larger observational studies with concurrent dietary data are needed to determine whether vitamin E has a modest but potentially important protective effect against colorectal cancer.

Adolescent

Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow-up of the Prospective Basel Study.

There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT TRUNCATED AT 400 WORDS)

Antioxidants

[Vitamins during high dose chemo- and radiotherapy].

Plasma from 22 patients was examined for alpha- and gamma-tocopherol (vitamin E), the carotenoids beta-carotene (provitamin A) and lycopene, retinol (vitamin A), and ascorbic acid (vitamin C) before, during and after conditioning chemotherapy for bone marrow transplantation, 18 of these received total body irradiation as well. In addition, alpha-tocopherol in red blood cell membranes was measured. Retinol and ascorbic acid have been applied in multiple of the recommended doses (Deutsche Gesellschaft für Ernährung and Recommended Dietary Allowance, respectively). The chosen doses were sufficient to maintain the initial plasma concentrations of these vitamins. However, alpha-tocopherol (in RDA doses) and beta-carotene (no RDA established) concentrations deteriorated after the conditioning therapy (20 and 50% loss, respectively). The loss of these lipid-soluble antioxidants has been considered to result from lipid peroxidation. On the basis of the presented results we propose intervention studies to investigate the effect of high dose antioxidant administration on the toxicity (mainly of liver and lung) of intensive antineoplastic therapy protocols.

Adolescent

Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel Study.

Plasma antioxidant vitamins A, C, and E and carotene were measured in a group of 2,974 men participating in the third examination of the prospective Basel Study in 1971-1973. In 1985, the vital status and mortality of all participants were assessed. A total of 204 men had died from cancer, including 68 with bronchus cancer and 37 with gastrointestinal cancer (20 with stomach cancer and 17 with large bowel cancer excluding cancer of the rectum). Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer also had lower mean vitamin C and lipid-adjusted vitamin A levels than did survivors (p less than 0.05). After calculation of the relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low plasma carotene (below quartile 1) was associated with a significantly increased risk for bronchus cancer (relative risk (RR) = 1.8, p less than 0.05), low plasma levels of carotene and vitamin A with all cancers (RR = 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than age 60 years) with lung cancer (RR = 2.17, p less than 0.05). Low levels of vitamin C increased the risk of stomach cancer (RR = 2.38) and gastrointestinal cancer (RR = 2.46) in older subjects, but only significantly with the inclusion of the first 2 years. The authors conclude that low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality. This effect was stronger in men above age 60 years at blood sampling, and the effect seems to be site-specific.

Adult

Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene.

The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54. Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina. There was no significant relation with vitamin A. Smoking was a confounding factor. The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking. Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight. The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02). These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E.

Adult

Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged.

Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor. Using stepwise regression statistical analysis, the variables age, cholesterol, cholesterol/total phospholipid and phosphatidyl ethanolamine/phosphatidyl choline molar ratios were all shown to have a significant positive influence on membrane microviscosity, whereas total phospholipids had a negative effect. No statistically significant difference was seen in content of any single saturated or unsaturated fatty acid between young and old donors. After pooling, however, the proportion of all unsaturated fatty acids was significantly higher in cells from the elderly as a consequence of an increase of n-6 and n-3 polyunsaturated fatty acids. Changes in lipid composition and physical properties of lymphocyte plasma membranes may, therefore, be responsible (at least partially) for the diminution of immune reactivity in old age.

Adult

Antioxidant vitamin intakes assessed using a food-frequency questionnaire: correlation with biochemical status in smokers and non-smokers.

The increasing interest in the possible role of antioxidant vitamins in many disease states means that methods of assessing vitamin intakes which are suitable for large-scale investigations are now required. The suitability of the food-frequency questionnaire, which was developed by the Medical Research Council - Cardiff Group, for determining dietary intake of antioxidant vitamins in epidemiological studies was investigated in 196 Scottish men. The validity of the dietary data was assessed by comparison with serum vitamin concentrations, and separate analyses were performed for current smokers and non-smokers. The results showed that total energy intake and the percentage of energy derived from sugar were higher in smokers, and that both dietary and serum values of vitamin C, beta-carotene and vitamin E were lower in smokers than non-smokers. After adjustment for serum lipids, energy intake and body mass index, correlation coefficients between dietary and serum vitamins C and E were similar for smokers (r 0.555 and 0.25 respectively) and non-smokers (r 0.58 and 0.32 respectively). Correlation between dietary and serum carotenes was reduced from 0.28 in non-smokers to 0.09 in smokers and correlations for retinol and total vitamin A were weakly significant only for non-smokers. The food-frequency questionnaire assigned greater than 70% of subjects correctly into the upper or lower plus adjacent tertiles of serum vitamin values, with the exception of beta-carotene and total vitamin A for smokers. Thus, the food-frequency questionnaire appeared to be an adequate tool for assigning individuals into tertiles of serum antioxidant vitamins with the main exception of beta-carotene for smokers. Marked differences do occur between the vitamins and between the smoking groups which may reflect reduced accuracy of reporting on the food-frequency questionnaire or differential absorption and metabolism of the vitamins.

Adult

Beta-carotene and cancer prevention: the Basel Study.

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Adult

Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology.

Essential antioxidants were determined in plasma of middle-aged men representing 16 European study populations, which differed sixfold in age-specific mortality from ischemic heart disease (IHD). In 12 populations with "common" plasma cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors lacked significant correlations to IHD mortality, whereas absolute levels of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). Evaluating all populations, cholesterol and diastolic blood pressure were moderately associated, but their correlation was inferior to that of vitamin E. In stepwise regression and multiple regression analysis, mortality was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol), and to 87% by all the above parameters plus blood pressure. Thus, in the present study the cross-cultural differences of IDH mortality are primarily attributable to plasma status of vitamin E, which might have protective functions.

Adult

The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms.

Plasma levels of major essential antioxidants were determined in representative random samples of middle-aged men from 16 European study populations which differed up to 6-fold in age-specific mortality from ischaemic heart disease (IHD). In 12 study populations having total plasma cholesterol in the medium range (5.7-6.2 mmol/l) and usual blood pressure, both these classical risk factors lacked a significant correlation to IHD mortality, whereas the absolute level of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). On evaluation of all study populations, cholesterol and diastolic blood pressure had a moderate direct association with IHD, but their importance still remained inferior to that of vitamin E as an inversely associated, presumably protective factor. In stepwise regression and multiple regression analysis, the IHD mortality of the study populations was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and total cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol) and to 87% by all the above parameters plus diastolic blood pressure. In conclusion, in the present study the plasma status of vitamin E is the most important factor to explain cross-cultural differences of IHD mortality. This finding is consistent with the hypothesis of the prevention of arteriosclerosis by antioxidant protection against peroxidative lipoprotein modification, but does not exclude additional effects of antioxidant vitamins, e.g. on the cellular or immunological level.

Adult

Plasma vitamin E and beta-carotene concentrations during radiochemotherapy preceding bone marrow transplantation.

Blood from 19 patients was examined for the essential antioxidants alpha-tocopherol and beta-carotene before, during, and after bone marrow transplantation (BMT). Marrow ablation and immunosuppression for BMT conditioning was achieved by treatment with high-dose chemotherapy, mostly combined with total body irradiation. All patients required total parenteral nutrition beginning 1 wk before BMT. After conditioning therapy the concentration of absolute and lipid-standardized alpha-tocopherol and beta-carotene in plasma decreased significantly, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early posttransplant organ toxicity.

Adolescent

Effect of etoposide (VP16-213) on lipid peroxidation and antioxidant status in a high-dose radiochemotherapy regimen.

A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2 +/- 60 mg/kg). Patients stratified to be at high risk for relapse (6/13) were additionally treated with etoposide (30 mg/kg). Plasma concentrations of absolute and lipid-standardized antioxidants (alpha-tocopherol and beta-carotene) decreased following conditioning therapy, presumably as the result of an enhanced breakdown of these antioxidants. Etoposide treatment did not amplify the loss of essential anti-oxidants but significantly increased lipid hydroperoxide concentrations in serum. We suggest that the abnormal generation of lipid hydroperoxides is the result of free radical formation.

Anemia, Aplastic

[Plasma vitamin A and E correlate inversely with coronary mortality].

All essential plasma antioxidants were measured in representative samples of apparently healthy males from 12 European study populations the coronary mortality of which differed by the factor 4. Lipid-standardized vitamins A and E showed a strong inverse correlation to the age-specific coronary mortality (r2 = 0.33 and r2 = 0.49, resp.; combined r2 = 0.53) and thus complemented substantially the direct correlation of coronary mortality with total cholesterol (r2 = 0.51). Multiple regression analysis with these three variables predicted the actual mortality almost completely (r2 = 0.94). In conclusion, a fair plasma status of vitamins A and E could be a quantitatively important, hitherto underrated protective factor of coronary heart disease. These antioxidant vitamins presumably protect lipoproteins against peroxidation and atherogenic modification, respectively, but might still have additional antiarteriosclerotic effects in the arterial wall.

Adult

Plasma vitamin E, apolipoprotein B and HDL-cholesterol in middle-aged men from southern Italy.

Plasma vitamin E, HDL-cholesterol, apolipoprotein B and triglycerides were measured in an apparently healthy, male, random population sample (n = 74) from Southern Italy. Plasma vitamin E concentration was positively correlated to that of serum cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B (all P less than 0.001). The results of partial correlation analysis showed that apo B, the apolipoprotein constituent of LDL, was related to vitamin E independently of serum triglycerides, a fairly accurate marker of VLDL. On the other hand, triglycerides were related to vitamin E independently of apo B. Both correlations were much weaker if an adjustment was performed for non-HDL-cholesterol. No independent relationship was demonstrated between plasma vitamin E and HDL-cholesterol.

Adult

Plasma vitamins E and A inversely correlated to mortality from ischemic heart disease in cross-cultural epidemiology.

In eight study populations in which the medians of total plasma cholesterol did not differ significantly (mean 5.8 mM, p greater than 0.05) and therefore did not correlate with the IHD mortality (r2 = 0.05), the median of absolute plasma level of vitamin E (alpha-tocopherol) was inversely related to the IHD mortality (r2 = 0.55; p = 0.003). Vitamin A behaved similarly (r2 = 0.51; p = 0.046). The absolute levels of vitamins E and A together with cholesterol predicted (by multiple regression analysis) the IHD mortality of these eight populations fairly well (r2 = 0.81; p = 0.06). Considering all 12 study populations analyzed thus far, total plasma cholesterol correlated with the IHD mortality directly as expected (r2 = 0.51; p less than 0.01), but the median of the plasma alpha-tocopherol individually standardized for cholesterol and triglycerides (220 mg/dL + 110 mg/dL, respectively) maintained a strong inverse association with the IHD mortality (r2 = 0.49; p = 0.01). In the partial regression analysis, lipid-standardized vitamin E exhibited an even stronger inverse correlation with IHD mortality (r2 = 0.69; p less than 0.001). Again, vitamin A behaved similarly to vitamin E, that is, after lipid-standardization of individuals (r2 = 0.33; p = 0.07), as well as in the cholesterol-independent partial regression analysis (r2 = 0.74; p less than 0.001). Both vitamins may act singularly, for after lipid-standardization they vary de facto independently (rs = 0.012) in individuals. The combination of vitamins E and A as obtained by multiple partial regression predicted the actual IHD mortality to a large extent (r2 = 0.89; p less than 0.001), whereas the three-variable prediction model, with the median of total cholesterol and of individually lipid-standardized vitamins E and A, fit the actual IHD mortality of these 12 populations almost completely (r2 = 0.94; p less than 0.001). In conclusion, the plasma status of vitamins E and A are important, hitherto underrated risk factors of IHD, which may act independently, but can, if combined, predict at least 53% of the cross-cultural differences of IHD mortality. After inclusion of total cholesterol into a multivariate model, up to 94% of the IHD mortality can be predicted. The present epidemiological data are in agreement with the hypothesis that these vitamins have physiological functions in the protection of lipoproteins against peroxidation and atherogenic apo-B modifications, respectively, but that does not exclude additional beneficial effects of vitamin E and A in the arterial wall.

Adult

Low plasma vitamins E and C. Increased risk of angina in Scottish men.

Cross-cultural studies suggest that low plasma antioxidant levels contribute to the high incidence of coronary heart disease (CHD) in Scotland. One hundred twenty-five cases of angina without reported history were identified by a postal WHO chest pain questionnaire from a systemic population sample of 6000 Edinburgh men (35-54 years). Classical CHD risk factors (lipids, blood pressure, smoking, and relative weight), plasma vitamins, and a new independent CHD risk factor, adipose tissue linoleate, were measured in angina (n = 125) and healthy controls (n = 430). Cigarette smoking was common in angina (46% vs. 29%, p less than 0.01), and adipose tissue linoleate was lower (8.77 +/- 0.18% vs. 9.81 +/- 0.14% (p less than 0.01). Classical CHD risk factors were not different. Vitamin E/cholesterol molar ratio (micron/mM) was lower in angina than in controls: 1.58 +/- 0.03 vs. 1.66 +/- 0.02 (p less than 0.01). Plasma vitamin C was also lower in angina than in controls: 23.6 +/- 1.7 vs. 30.5 +/- 1.1 microM (p less than 0.001). The relative risk of angina for those in the lowest versus those in the highest quintile of the vitamin E/cholesterol ratio distribution was 2.2:1, irrespective of other risk factors (p less than 0.009). Adipose tissue linoleate removed the association between vitamin E and angina. The relative risk of angina for those in the lowest versus those in the highest quintile of plasma vitamin C was 2.6:1 (p less than 0.01), and the increased risk was also independent of classical risk factors, but closely related to a smoking habit. Low plasma vitamin E or adipose linoleate predisposes to angina, and smoking may increase the risk of angina by lowering plasma vitamin C levels in Scottish men.

Adult