Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial.

Antioxidants may retard atherogenesis and limit inflammatory processes involved in aneurysm formation. We evaluated effects of alpha-tocopherol and beta-carotene supplementation on incidence of large abdominal aortic aneurysm (AAA) in a randomised, double-blind, placebo-controlled trial. Subjects (n=29133) were 50-69-years-old male smokers, participants in the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study. They were randomised to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo in a 2x2 design. Incidence of AAA was evaluated from mortality and hospital registers. During 5.8 years of follow-up, 181 men were diagnosed with either ruptured AAA (n=77) or nonruptured large AAA treated with aneurysmectomy (n=104). Relative risk (RR) for AAA was 0.83 (95% confidence interval [CI] 0.62-1.11) among men receiving alpha-tocopherol compared with those who did not, and 0.93 (95% CI 0.69-1.24) among men receiving beta-carotene compared with those who did not. A modest though nonsignificant decrease in risk for nonruptured AAA was observed among alpha-tocopherol supplemented men (RR 0.71, 95% CI 0.48-1.04) compared with men not receiving alpha-tocopherol. For beta-carotene, RR for nonruptured AAA was 0.86 (95% CI 0.59-1.27) compared with men not receiving beta-carotene. Neither antioxidant affected risk for ruptured AAA. In conclusion, long-term supplementation with alpha-tocopherol or beta-carotene had no preventive effect on large AAA among male smokers.

Life-style factors and risk for abdominal aortic aneurysm in a cohort of Finnish male smokers.

Prospective studies evaluating risk factors for abdominal aortic aneurysm are few. We studied the association of life-style factors with risk for abdominal aortic aneurysm among 29,133 male smokers 50-69 years of age, participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. During a mean follow-up of 5.8 years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured abdominal aortic aneurysm plus aneurysmectomy. Risk for abdominal aortic aneurysm was positively associated with age [relative risk (RR) = 4.56, 95% confidence interval (CI) = 2.42-8.61 for > 65 vs < or = 55 years], smoking years (RR = 2.25, 95% CI = 1.33-3.81 for > 40 vs < or = 32 years), systolic blood pressure (RR = 1.92, 95% CI = 1.13-3.25 for > 160 vs < or = 130 mmHg), diastolic blood pressure (RR = 1.80, 95% CI = 1.05-3.08 for > 100 vs < or = 85 mmHg), and serum total cholesterol (RR = 1.85, 95% CI = 1.09-3.12 for > 6.5 vs < or = 5.0 mmol/liter). High-density lipoprotein cholesterol showed a strong inverse association with risk for aortic aneurysm (RR = 0.16, 95% CI = 0.08-0.32 for > 1.5 vs < or = 0.9 mmol/liter). High energy intake was associated with lower risk for aortic aneurysm (RR = 0.59, 95% CI = 0.38-0.94 for the highest quartile vs the lowest), whereas no associations with nutrients were evident. We conclude that classical risk factors for atherosclerotic diseases seem to be important in pathogenesis of large abdominal aortic aneurysms.

Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group.

BACKGROUND AND AIMS: The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. MATERIAL AND METHODS: The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. RESULTS: Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). CONCLUSIONS: We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Prospective study of diet, lifestyle, and intermittent claudication in male smokers.

The association between dietary and lifestyle factors and intermittent claudication was investigated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort comprised 26,872 male smokers aged 50-69 years who were free of claudication at study entry. At baseline (1985-1988), subjects completed a diet history questionnaire. During a median follow-up period of 4 years (ending in spring 1993), 2,578 men reported symptoms of claudication on the Rose questionnaire, which was administered annually. Smoking status was assessed every 4 months. Smoking, systolic blood pressure, serum total cholesterol, and diabetes mellitus were positively associated with risk for claudication, whereas serum high density lipoprotein cholesterol, education, and leisure time exercise were inversely associated with risk. Dietary carbohydrates, fiber, and n-6 polyunsaturated fatty acids were inversely associated with risk for claudication, as were some dietary and serum antioxidants: dietary vitamin C (highest quartile vs. lowest: relative risk (RR) = 0.86; 95% confidence interval (CI): 0.77, 0.97), dietary gamma-tocopherol (RR = 0.89; 95% CI: 0.79, 1.00), dietary carotenoids (RR = 0.82; 95% CI: 0.73, 0.92), serum alpha-tocopherol (RR = 0.88; 95% CI: 0.77, 1.00), and serum beta-carotene (RR = 0.77; 95% CI: 0.68, 0.86). Smoking cessation reduced subsequent risk for claudication (RR = 0.86; 95% CI: 0.75, 0.99). The authors conclude that classical risk factors for atherosclerosis are associated with claudication. High intakes of antioxidant vitamins may be protective. Further research is needed before antioxidants can be recommended for the prevention of intermittent claudication.

Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers.

Observational data suggest that diets rich in fruits and vegetables and with high serum levels of antioxidants are associated with decreased incidence and mortality of stroke. We studied the effects of alpha-tocopherol and beta-carotene supplementation. The incidence and mortality of stroke were examined in 28 519 male cigarette smokers aged 50 to 69 years without history of stroke who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). The daily supplementation was 50 mg alpha-tocopherol, 20 mg beta-carotene, both, or placebo. The median follow-up was 6.0 years. A total of 1057 men suffered from incident stroke: 85 men had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. Deaths due to stroke within 3 months numbered 38, 50, 65, and 7, respectively (total 160). alpha-Tocopherol supplementation increased the risk of subarachnoid hemorrhage 50% (95% CI -3% to 132%, P=0.07) but decreased that of cerebral infarction 14% (95% CI -25% to -1%, P=0.03), whereas beta-carotene supplementation increased the risk of intracerebral hemorrhage 62% (95% CI 10% to 136%, P=0.01). alpha-Tocopherol supplementation also increased the risk of fatal subarachnoid hemorrhage 181% (95% CI 37% to 479%, P=0.01). The overall net effects of either supplementation on the incidence and mortality from total stroke were nonsignificant. alpha-Tocopherol supplementation increases the risk of fatal hemorrhagic strokes but prevents cerebral infarction. The effects may be due to the antiplatelet actions of alpha-tocopherol. beta-Carotene supplementation increases the risk of intracerebral hemorrhage, but no obvious mechanism is available.

Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland).

OBJECTIVES: Epidemiological studies have suggested a protective effect of vegetables and fruits on urinary tract cancer but the possible protective nutrients are unknown. We studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation on urinary tract cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. METHODS: A total of 29,133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years (median 6.1 years). Incident urothelial cancers (bladder, ureter, and renal pelvis; n = 169) and renal cell cancers (n = 102) were identified through the nationwide cancer registry. The diagnoses were centrally confirmed by review of medical records and pathology specimens. The supplementation effects were estimated using a proportional hazards model. RESULTS: Neither alpha-tocopherol nor beta-carotene affected the incidence of urothelial cancer, relative risk 1.1 (95% confidence interval (CI) 0.8-1.5) and 1.0 (95% CI 0.7-1.3), respectively, or the incidence of renal cell cancer, relative risk 1.1 (95% CI 0.7-1.6) and 0.8 (95% CI 0.6-1.3), respectively. CONCLUSION: Long-term supplementation with alpha-tocopherol and beta-carotene has no preventive effect on urinary tract cancers in middle-aged male smokers.

The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial.

We evaluated the effect of long-term supplementation with vitamin E (alpha-tocopherol) and beta-carotene on occurrence of claudication symptoms and risk for peripheral vascular surgery among men with intermittent claudication. Subjects, 50-69-year old male smokers, were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who reported intermittent claudication through a structured questionnaire (Rose) at study entry (n=1484). They were randomly assigned to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo, in a 2 x 2 design. During follow-up, claudication was evaluated by repeating use of the questionnaire once a year. Information on peripheral vascular surgery came from the National Hospital Discharge Register. We observed no effect of alpha-tocopherol and beta-carotene supplementation on claudication during a mean follow-up of 3.7 years. A slightly increased risk (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.05-2.44) for vascular surgery was observed among beta-carotene supplemented men compared to those who did not receive beta-carotene. Alpha-tocopherol supplementation had no effect. In conclusion, long-term supplementation with alpha-tocopherol and beta-carotene showed no beneficial effect on symptoms and progression of intermittent claudication.

The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers.

Epidemiological and experimental studies have indicated that dietary factors such as vitamin C, vitamin E, and beta-carotene are associated with the risk of colorectal cancer. This study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study), whose participants were randomly assigned to four supplementation groups: (a) alpha-tocopherol (AT), 50 mg/day; (b) beta-carotene (BC), 20 mg/day; (c) both AT and BC; and (d) placebo. We included the 15,538 ATBC Study participants who had been randomized within the areas of three major cities in southern Finland. Cases of colorectal adenoma (n = 146) were identified by the pathology laboratories in the study areas, and these participants' medical records were collected and reviewed. Alpha-tocopherol supplementation increased the risk for adenomas (relative risk, 1.66; 95% confidence interval, 1.19-2.32), whereas beta-carotene supplementation had no effect on the risk (relative risk, 0.98; 95% confidence interval, 0.71-1.35). Slightly more prediagnosis rectal bleeding and intestinal pain occurred in those adenoma cases who received alpha-tocopherol supplements than in those who did not. Thus, some bias may have resulted, with alpha-tocopherol supplementation leading to more colonoscopies and, thus, to an increased detection of incident polyps in this group. This is further supported by the trial finding that alpha-tocopherol supplementation did not increase the risk of colorectal cancer.

Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study.

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Effects of alpha tocopherol and beta carotene supplements on symptoms, progression, and prognosis of angina pectoris.

OBJECTIVE: To evaluate the effects of alpha tocopherol and beta carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris. DESIGN: Placebo controlled clinical trial. SETTING: The Finnish alpha tocopherol beta carotene cancer prevention study primarily undertaken to examine the effects of alpha tocopherol and beta carotene on cancer. SUBJECTS: Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795). INTERVENTIONS: alpha tocopherol (vitamin E) 50 mg/day, beta carotene 20 mg/day or both, or placebo in 2 x 2 factorial design. MAIN OUTCOME MEASURES: Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease). RESULTS: There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: alpha tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), alpha tocopherol and beta carotene 1.02 (0.82 to 1.27), beta carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo. CONCLUSIONS: There was no evidence of beneficial effects for alpha tocopherol or beta carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

Tissue stores of individual monounsaturated fatty acids and breast cancer: the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

The strongest evidence that monunsaturated fat may influence breast cancer risk comes from studies of southern European populations, in whom intake of oleic acid sources, particularly olive oil, appears protective. No previous study has examined the relation of adipose tissue fatty acid content to breast cancer in such a population. We used adipose biopsies with diverse fat intake patterns gathered in 5 European centers, including southern Europe (Malaga, Spain), to test the hypothesis that stores of oleic acid or other monounsaturates are inversely associated with breast cancer. Gluteal fat aspirates were obtained from 291 postmenopausal incident breast cancer patients and 351 control subjects, frequency-matched for age and catchment area. Logistic regression was used to model breast cancer by monounsaturates, with established risk factors controlled for. Oleic acid showed a strong inverse association with breast cancer in the Spanish center. The odds ratio for the difference between 75th and 25th percentiles was 0.40 (95% CI: 0.28, 0.58) in Malaga and 1.27 (0.88, 1.85) in all other centers pooled, with a peak at 2.36 (1.01, 5.50) for Zeist. Palmitoleic and myristoleic acids showed evidence of an inverse association outside Spain, and cis-vaccenic acid showed a positive association in 3 centers. These data do not support the hypothesis that increasing tissue stores of oleic acid are protective against breast cancer in non-Spanish populations. This finding implies that the strong protective associations reported for olive oil intake in dietary studies may be due to some other protective components of the oil and not to the direct effect of oleic acid uptake. Alternatively, high olive oil intake may indicate some other protective aspect of the lifestyle of these women.

Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease.

BACKGROUND: Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis. In epidemiological studies antioxidants have been inversely related with coronary heart disease. Findings from controlled trials are inconclusive. METHODS: We studied the primary preventive effect of vitamin E (alpha tocopherol) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial undertaken primarily to examine the effects of these agents on cancer. A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20 mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end point was the first major coronary event, either nonfatal myocardial infarction (surviving at least 28 days; n = 1204) or fatal coronary heart disease (n = 907). RESULTS: The incidence of primary major coronary events decreased 4% (95% confidence interval, -12% to 4%) among recipients of vitamin E and increased 1% (95% confidence interval, -7% to 10%) among recipients of beta carotene compared with the respective nonrecipients. Neither agent affected the incidence of nonfatal myocardial infarction. Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to 5%), but beta carotene had no effect on this end point. CONCLUSIONS: Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infarction, but no influence on nonfatal myocardial infarction. Supplementation with beta carotene has no primary preventive effect on major coronary events.

Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels.

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.

Gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene. The Helsinki Gastritis Study Group.

BACKGROUND: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis. METHODS: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years. RESULTS: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates. CONCLUSIONS: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.

Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.

The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms.

The effects of alpha-tocopherol (50 mg/d) and beta-carotene (20 mg/d) supplementation on symptoms of chronic obstructive pulmonary disease were studied among the 29,133 participants of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study undertaken to investigate the effects of these two substances in the prevention of lung and other cancers. During the follow-up the supplementations did not affect the recurrence or incidence of chronic cough, phlegm, or dyspnea. The prevalence of chronic bronchitis and dyspnea at baseline was lower among those with high dietary intake of beta-carotene (OR = 0.78 and 0.67, respectively) or vitamin E (OR = 0.87 and 0.77) and high serum beta-carotene (OR = 0.59 and 0.62) and alpha-tocopherol (OR = 0.76 and 0.82). High intake and serum levels of retinol were associated with low prevalence of dyspnea (OR = 0.84 and 0.80, respectively) but not with chronic bronchitis. The results indicate no benefit from supplementation with alpha-tocopherol or beta-carotene on the symptoms of chronic obstructive pulmonary disorders but support the beneficial effect of dietary intake of fruits and vegetables rich in these compounds.

Lycopene and myocardial infarction risk in the EURAMIC Study.

A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.