Association of serum α-tocopherol, ß-carotene, and retinol with liver cancer incidence and chronic liver disease mortality.

BACKGROUND: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, ß-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. METHODS: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. RESULTS: Higher ß-carotene and retinol levels were associated with less liver cancer (ß-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of ß-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. CONCLUSIONS: Our findings suggest that higher concentrations of ß-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

Effects of α-tocopherol and ß-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

BACKGROUND: Recent data suggest the possible benefits of α-tocopherol and ß-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. METHODS: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) ß-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. RESULTS: Supplemental α-tocopherol, ß-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. CONCLUSIONS: Long-term supplemental α-tocopherol or ß-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. METHODS: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. CONCLUSION: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Intake of antioxidants and risk of type 2 diabetes in a cohort of male smokers.

BACKGROUND/OBJECTIVES: Oxidative stress may induce insulin resistance in peripheral tissues and impair insulin secretion from pancreatic ß-cells. Antioxidants are suggested to decrease the risk of diabetes through reduction of oxidative stress. However, only a few studies exist on dietary antioxidants and the risk of type 2 diabetes. We investigated the association of dietary antioxidants with incident type 2 diabetes in the α-Tocopherol, ß-Carotene Cancer Prevention Study cohort. SUBJECT/METHODS: The study cohort included 29,133 male smokers aged 50-69 years. During a median follow-up of 10.2 years 660 incident cases of diabetes were observed among the 25,505 men with a completed baseline food frequency questionnaire. RESULTS: Dietary α-tocopherol, ß-tocopherol and ß-tocotrienol were positively associated with the risk of diabetes when adjusted for age and supplementation (relative risk (RR) 1.17 (95% confidence interval (CI) 0.91-1.51) P for trend 0.02; RR 1.31 (95% CI 1.02-1.68) P for trend 0.01; RR 1.28 (95% CI 1.00-1.63) P for trend 0.01, respectively), but the association disappeared after multivariate adjustment (RR 0.92 (95% CI 0.71-1.19) P for trend 0.97; RR 1.06 (95% CI 0.82-1.36) P for trend 0.48; RR 1.04 (95% CI 0.80-1.35) P for trend 0.46, respectively). Other tocopherols and tocotrienols as well as vitamin C, carotenoids, flavonols and flavones had no association with risk of diabetes. CONCLUSIONS: Dietary antioxidants were not associated with a decreased risk of incident diabetes in middle-aged male smokers.

Dietary acrylamide intake and the risk of cancer among Finnish male smokers.

OBJECTIVE: To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. METHODS: The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. RESULTS: During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. CONCLUSIONS: High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether alpha-tocopherol or beta-carotene affected the occurrence of type 2 diabetes. METHODS: In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for alpha-tocopherol and beta-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. RESULTS: Baseline serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of alpha-tocopherol was 1.59 (95% CI 0.89-2.84) and that for beta-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving alpha-tocopherol compared with non-recipients and 0.99 (95% CI 0.85-1.15) for participants receiving beta-carotene compared with non-recipients. CONCLUSIONS/INTERPRETATION: Neither alpha-tocopherol nor beta-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of type 2 diabetes.

Physical activity and the risk of pneumonia in male smokers administered vitamin E and beta-carotene.

It has been proposed that moderate exercise may enhance the immune system. We evaluated whether physical activity at work or at leisure is associated with the risk of pneumonia, and whether the antioxidants vitamin E and beta-carotene affect pneumonia risk in physically active people. A cohort of 16 804 male smokers aged 50-69 years and working at study entry was drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the effect of vitamin E, 50 mg/day, and beta-carotene, 20 mg/day, on lung and other cancers. Physical activity at work, and the type of leisure-time exercise, were recorded at study entry. We retrieved the first occurrence of hospital-treated pneumonia during a 3-year follow-up from the National Hospital Discharge Register (133 cases). Physical activity at work and at leisure had no association with the risk of pneumonia. In participants with physically loading jobs, neither vitamin E nor beta-carotene affected the risk of pneumonia. In participants carrying out moderate or heavy exercise at leisure, beta-carotene had no effect, but vitamin E reduced the risk of pneumonia by 50% (95% CI: 16-70%). Previously, exercise has been shown to affect diverse laboratory measures of the immune system which are, however, only surrogate markers for the resistance to infections. The lack of association between physical activity and the risk of pneumonia observed in our study emphasizes the problem of drawing conclusions from surrogate end points. The finding that vitamin E reduced the risk of pneumonia in persons carrying out leisure-time exercise warrants further study.

Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers.

OBJECTIVE: To study the association between dietary and serum antioxidant vitamins and carotenoids and risk for colorectal cancer in male smokers. DESIGN: A prospective cohort study within a randomised, double-blind, placebo-controlled trial testing supplementation with alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day) or both in preventing cancer. SUBJECTS AND METHODS: Participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study with complete dietary data and serum samples available from baseline. These included 26,951 middle-aged male smokers among whom 184 colorectal cancer cases were diagnosed during 8 y of follow-up. Relative risks were calculated with Cox proportional hazards models adjusting for trial supplementation, age, body mass index, serum cholesterol, cigarettes smoked per day and physical activity. RESULTS: There was no significant association between dietary vitamin C or E, alpha-or gamma-tocopherol, retinol, alpha- or beta-carotene, lycopene or lutein+zeaxanthin and risk for colorectal cancer. Serum alpha-tocopherol, beta-carotene or retinol was also not associated with the risk, neither did the season when baseline blood was drawn modify the relationship between serum beta-carotene and colorectal cancer risk. CONCLUSIONS: Our data support the results from previous studies in which no association between dietary antioxidant vitamins and carotenoids and risk for colorectal cancer has been observed. Likewise, no association between baseline serum antioxidant concentrations and colorectal cancer risk was evident. SPONSORSHIP: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by a contract with the US National Cancer Institute (N01-CN-45165).

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.

Influence of antioxidants and the CYP1A1 isoleucine to valine polymorphism on the smoking--lung cancer association.

To evaluate the association between CYP1A1 genotype and lung cancer risk and to assess the effect of CYP1A1 genotype and antioxidant supplementation on the smoking--lung cancer relationship we conducted a case-control study nested within a large cancer prevention trial cohort. Controls (n = 324) were matched to cases (n = 282) on age (+/- 5 years), intervention group and study clinic in a 1:1 ratio, using incidence density sampling. Genotype was determined by a PCR-based method and logistic regression was used to calculate relative risk estimates. Overall, we found no association between CYP1A1 genotype and lung cancer risk. CYP1A1 genotype did not modify the effect of smoking on lung cancer risk. However, in an examination of subgroups defined by randomized intervention assignment our findings suggest that alpha-tocopherol supplementation may reduce the risk of lung cancer associated with cumulative smoking exposure regardless of CYP1A1 genotype with the greatest effect seen among those with the variant CYP1A1 allele.

Helicobacter pylori seropositivity as a risk factor for pancreatic cancer.

BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer.

Educational differences in lung cancer mortality in male smokers.

BACKGROUND: To assess the extent of lung cancer mortality differentials by education while adjusting for exposure to tobacco smoke and asbestos based on survey questions. METHODS: Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) Study of 50-69-year-old Finnish male smokers enrolled 1985-1988. These analyses are based on the placebo group and the alpha-tocopherol supplementation group, altogether 14 011 men, with full information on tobacco smoking. Mortality follow-up was to the end of April 1993 and it was based on the complete death certificate register of the Statistics Finland. RESULTS: Lung cancer mortality of basic-educated men was 32% (rate ratio [RR] = 1.32; 95% CI : 0.93-1.87) higher than that of better-educated men in the ATBC Study. The excess is practically unchanged when additional adjustment was made for age at initiation, duration of smoking, current smoking at baseline and at first follow-up, smoke inhalation, occupational exposure to asbestos and interactions between asbestos exposure and all smoking variables. This excess mortality was about 40% of the similar excess observed in the general population of men of similar age. CONCLUSIONS: Educational differences in lung cancer mortality in the total Finnish population are likely to be mainly caused by differences in exposure, particularly to active smoking. Further understanding of the determinants and consequences of socioeconomic differences in smoking behaviour are of major scientific and public health importance.

Effects of long-term alpha-tocopherol supplementation on serum hormones in older men.

BACKGROUND: alpha-tocopherol supplementation significantly reduced risk of prostate cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. Sex hormones are thought to be involved in the etiology of prostate cancer. We examined whether long-term supplementation with alpha-tocopherol modified serum hormone levels. METHODS: Men who were cancer-free consumed > or = 90% of the study capsules, and who had both baseline and follow-up blood available, were eligible for the study. One hundred men who received alpha-tocopherol were matched on age, study center, and length of time between blood draws to 100 men who received a placebo. Multivariate linear regression models which allowed for a separate intercept for each matched pair were used to evaluate the effect of alpha-tocopherol supplementation on follow-up hormone concentrations. RESULTS: Compared to men who received a placebo, we found significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentrations among men who received alpha-tocopherol, after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking, and fasting time. Geometric mean (95% confidence interval; CI) androstenedione concentration among men who received alpha-tocopherol was 145 ng/dl (CI, 137-153) after adjusting for covariates, compared to 158 ng/dl (CI, 148-167) among men who received a placebo. Mean testosterone concentrations for men who received alpha-tocopherol and placebo were 539 (CI, 517-562) and 573 (CI, 549-598) ng/dl, respectively. CONCLUSIONS: These results suggest that long-term alpha-tocopherol supplementation decreases serum androgen concentrations, and could have been one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha-tocopherol treatment group of the ATBC Study.

Intake of flavonols and flavones and risk of coronary heart disease in male smokers.

Flavonols and flavones are antioxidant polyphenolic compounds found in tea, vegetables, fruits, and wine. In experimental studies they have been effective free radical scavengers, metal chelators, and antithrombotic agents. In the few epidemiologic studies of these agents, some have suggested an inverse association between intake of flavonols and flavones and the risk of cardiovascular disease. Our study population comprised 25,372 male smokers, 50-69 years of age, with no previous myocardial infarction. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, which was a randomized, double-blind, placebo-controlled trial with daily supplementation of alpha-tocopherol (50 mg per day) and/or beta-carotene (20 mg per day). The men completed a validated dietary questionnaire at baseline. After 6.1 years of follow-up, there were 1,122 nonfatal myocardial infarctions and 815 coronary deaths. In the multivariate model, the relative risk of nonfatal myocardial infarction was 0.77 (95% confidence interval = 0.64-0.93) among men in the highest (median 18 mg per day) compared with the lowest (median 4 mg per day) quintile of flavonol and flavone intake. The respective relative risk for coronary death was 0.89 (95% confidence interval = 0.71-1.11). Thus, intake of flavonols and flavones was inversely associated with nonfatal myocardial infarction, whereas there was a weaker association with coronary death.

Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland).

BACKGROUND: Calcium, phosphorus, fructose, and animal protein are hypothesized to be associated with prostate cancer risk, potentially via their influence on 1,25-dihydroxyvitamin D3. We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC Study). MATERIALS AND METHODS: The ATBC Study was a randomized 2 x 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers; 27,062 of the men completed a food-use questionnaire at baseline, and comprise the current study population. There were 184 incident clinical (stage 2-4) prostate cancer cases diagnosed between 1985 and 1993. We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer. RESULTS: We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk. However, men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 (95% CI 0.3-1.0) compared to men with lower intakes of both nutrients, adjusting for age, smoking, body mass index, total energy, education, and supplementation group. Of the other foods and nutrients examined, none was significantly associated with risk. DISCUSSION: This study provides, at best, only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk, but suggests that there may be an interaction between these nutrients.

Vitamin E and beta carotene supplementation in high risk for stroke: a subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

CONTEXT: High serum or dietary levels of vitamin E and beta carotene appear to be associated with lower risk of stroke, but studies regarding their supplementation have not supported their use in stroke prevention. OBJECTIVE: To determine if vitamin E (dl-alpha tocopherol) and beta carotene supplementations could be used in prevention of stroke in men at high risk for hemorrhagic or ischemic events. DESIGN: Population-based, randomized, double-blind, placebo-controlled, 2 x 2 factorial design trial (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study), conducted from April 1985 through April 30, 1993, with median follow-up of 6 years. INTERVENTIONS: Alpha tocopherol, 50 mg; beta carotene, 20 mg; both; or placebo. PARTICIPANTS: From the total male population aged 50 through 69 years in southwestern Finland (n = 290,406), 29,133 male smokers were randomized to 1 of 4 treatment regimens. We excluded 614 men because of previous stroke at baseline, leaving 28, 519. MAIN OUTCOME MEASURES: Incident and fatal subarachnoid and intracerebral hemorrhage, cerebral infarction, and unspecified stroke. RESULTS: Stroke occurred in a total of 1057 men: 85 had subarachnoid and 112 had intracerebral hemorrhage, 807 had cerebral infarction, and 53 had unspecified stroke. Within 90 days from onset, 160 men died of stroke. Vitamin E supplementation increased the risk of subarachnoid hemorrhage (relative risk [RR], 2.45; 95% confidence interval [CI], 1.08-5.55) and decreased risk of cerebral infarction (RR, 0.70; 95% CI, 0.55-0.89) in hypertensive men but had no effect among normotensive men. Furthermore, it decreased the risk of cerebral infarction, without elevating the risk of subarachnoid hemorrhage, among hypertensive men with concurrent diabetes (RR, 0.33; 95% CI, 0.14-0.78). Beta carotene supplementation appeared to increase the risk of intracerebral hemorrhage and modestly decrease that of cerebral infarction among men with greater alcohol consumption. CONCLUSION: Vitamin E supplementation may prevent ischemic stroke in high-risk hypertensive patients, but further studies are needed. Arch Neurol. 2000;57:1503-1509

Serum CD44 levels preceding the diagnosis of non-Hodgkin's lymphoma.

Serum CD44 (s-CD44) concentrations were measured in sera taken from 49 individuals who were diagnosed with non-Hodgkin's lymphoma 0.9 to 7.2 years after taking the blood sample, and from 49 controls matched for age. The serum samples had been collected in conjunction of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, which evaluated the influence of vitamin supplementation on cancer prevention. S-CD44 was measured using chemiluminescence enzyme immunoassay. S-CD44 concentrations of the cases were significantly elevated before the diagnosis of lymphoma when compared to the serum levels found in the controls (median, 447 ng/mL; range, 108-780 ng/mL vs. median, 364 ng/mL; range, 53-660 ng/mL; p=0.012). Individuals who were later diagnosed with high grade lymphoma according to the Kiel classification (n=21) had significantly higher values than the controls 0.9-4.0 years before the diagnosis, but such a difference could not be detected if serum samples had been taken more than 4 years before the diagnosis. The s-CD44 levels were not significantly elevated among individuals who were later diagnosed with low grade malignant non-Hodgkin's lymphoma (n=25) as compared to their controls. The prediagnostic s-CD44 levels in cases and controls overlapped markedly, and a value higher than the highest value found among the controls (660 ng/mL) was found only in 5 (10%) samples taken from individuals who were later diagnosed with lymphoma. We conclude that serum CD44 may be elevated a few years preceding the diagnosis of non-Hodgkin's lymphoma, but the levels overlap markedly with those found in individuals without lymphoma.

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.