Search

Greater adult height, which reflects a combination of early nutrition, exposure to androgens, growth hormones, and other factors during growth and development, as well as heredity, has been associated with increased prostate cancer risk in several observational studies, but findings have been inconsistent. We examined this relationship in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline, 29,119 Finnish male smokers 50 to 69 years old had height and weight measured by trained personnel, provided information on demographic, smoking, medical, and other characteristics, and completed an extensive diet history questionnaire. A total of 1,346 incident prostate cancer cases were identified during a follow-up period of up to 17.4 years (median, 14.1 years). In age-adjusted Cox proportional hazards models, the hazard ratios and 95% confidence intervals for prostate cancer according to increasing quintiles of height [≤168, 169-171, 172-175, 176-178, and >178 cm] were 1.00 (reference), 1.11 (0.93-1.32), 1.11 (0.95-1.31), 1.30 (1.01-1.55), and 1.14 (0.96-1.35); Ptrend = 0.04. In analyses stratified by disease stage (available for 916 cases), a strong dose-response relationship was observed between greater height and advanced, but not earlier-stage, disease [tumor-node-metastasis stage III-IV, hazard ratio and 95% confidence interval for increasing quintiles of height: 1.77 (1.18-2.65), 1.82 (1.25-2.65), 1.93 (1.29-2.90), and 2.02 (1.37-2.97); Ptrend = 0.0008, Pinteraction = 0.002]. Our study provides additional evidence that increased height is a risk factor for prostate cancer and suggests that taller men are particularly susceptible to advanced disease. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2174–8)

BACKGROUND A meta-analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation. Little is known, however, about the relation between mortality and circulating concentrations of vitamin E resulting from dietary intake, low-dose supplementation, or both. OBJECTIVE We examined whether baseline serum alpha-tocopherol concentrations are associated with total and cause-specific mortality. DESIGN A prospective cohort study of 29 092 Finnish male smokers aged 50-69 y who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was carried out. Fasting serum alpha-tocopherol was measured at baseline by using HPLC. Only 10% of participants reported vitamin E supplement use at baseline, and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors. Risks of total and cause-specific mortality were estimated by using proportional hazards models. RESULTS During up to 19 y of follow-up, 13 380 deaths (including 4518 and 5776 due to cancer and cardiovascular disease, respectively) were identified. Men in the higher quintiles of serum alpha-tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [relative risk (RR) = 0.82 (95% CI: 0.78, 0.86) for total mortality and 0.79 (0.72, 0.86), 0.81 (0.75, 0.88), and 0.70 (0.63, 0.79) for deaths due to cancer, cardiovascular disease, and other causes, respectively; P for trend for all < 0.0001]. Cubic regression spline analysis of continuous serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to approximately 13-14 mg/L, after which no further benefit was noted. CONCLUSION Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers.

Background: Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case – control study of H. pylori serology to address these questions. Methods: Case and control subjects were selected from the 29 133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fi t conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confi dence intervals (CIs) for the association of H. pylori seropositivity, defi ned as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. Results: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically signifi cantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori – positive participants of this cohort would be 63 and 12 per 100 000 person-years, respectively, whereas corresponding rates in H. pylori – negative participants would be 8 and 37 per 100 000 person-years, respectively. Conclusion: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These fi ndings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries. [J Natl Cancer Inst 2006;98: 1445 – 52 ]

Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer. Anthropometric measures (height, weight, and body mass index (weight (kg)/height (m)(2)) and metabolic abnormalities associated with insulin resistance syndrome (IRS) (abnormalities in measured blood pressure, high density lipoprotein (HDL) cholesterol, and total cholesterol) were prospectively evaluated for associations with incident colon (n = 227), rectal (n = 183), and colorectal (n = 410) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. In comparison with the lowest quintile, the highest quintile of body mass index was significantly associated with colorectal cancer (hazard ratio (HR) = 1.70, 95% confidence interval (CI): 1.01, 2.85; p-trend = 0.01), particularly colon cancer. Subjects with a cluster of three IRS-related conditions (hypertension, body mass index >/=25 kg/m(2), and HDL cholesterol level

The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of participants in the Carotene and Retinol Efficacy Trial of lung cancer prevention. We assessed the validity of the Bach model among 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The expected numbers of lung cancer cases and deaths without lung cancer were calculated from the Bach model and compared with the observed numbers of corresponding events over 10 years. We found that the risk model slightly underestimated the observed lung cancer risk (number of lung cancers expected/number observed = 0.89, 95% confidence interval [CI] = 0.80 to 0.99) over 10 years. The competing risk portion of the model substantially underestimated risk of non-lung cancer mortality (number of non-lung cancer deaths expected/number observed = 0.61, 95% CI = 0.57 to 0.64) over 10 years. The age-specific concordance indices for 10-year predictions were 0.77 (95% CI = 0.70 to 0.84), 0.59 (95% CI = 0.53 to 0.65), 0.62 (95% CI = 0.57 to 0.67), and 0.57 (95% CI = 0.49 to 0.67) for the age groups 50-54, 55-59, 60-64, and 65-69 years, respectively. Periodic radiographic screening in the ATBC Study may explain why slightly more cancers were observed than expected from the Bach model.

A total of 29,133 male smokers, aged 50-69 years, were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in 1984-1988. The nationwide Finnish Cancer Registry (FCR) recorded 5944 incident cases of cancer in this cohort through the end of 1999. Compared with the FCR data of the entire Finnish male population of same age the standardized incidence ratio (SIR) of total cancer in the ATBC cohort was 1.55 [95% confidence interval (CI) 1.51-1.59]. There was a significant excess of established smoking-related malignancies, such as lung cancer (SIR 2.45, 95% CI 2.35-2.56), and cancers of the tongue, mouth, pharynx, larynx, oesophagus, pancreas, stomach, liver, urinary bladder and kidney. In addition to these sites, cancers of the prostate and colon were slightly more common in the ATBC cohort than in the total Finnish male population (SIR 1.10, 95% CI 1.04-1.18 and SIR 1.14, 95% CI 1.00-1.30, respectively). In conclusion, the risk of many cancers was significantly higher in the ATBC Study cohort compared with the total Finnish male population of same age. In addition to the well known smoking-related cancers, cigarette smoking may increase slightly the risk of colon and prostate cancer, too.

Helicobacter pylori infection is an important risk factor for gastric cancer, but

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk. (c) 2005 Wiley-Liss, Inc.

In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the alpha-tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR = 0.4, 95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR = 0.2, 95% CI = 0.1-0.7, p trend = 0.02; OR = 0.2, 95% CI = 0.1-0.9, p trend = 0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend = 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Low urine pH may be an important risk factor for bladder cancer, although few studies have evaluated this association. We examined the relationship between estimated renal net acid excretion (NAE), an indirect measure of urine pH based on nutrient intake and anthropometry, and bladder cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.At baseline, 27,096 male smokers 50-69 years old completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months, had height and weight measured, and provided a history of smoking. A total of 446 incident bladder cancer cases were identified during up to 17.4 years of follow-up.In multivariate proportional hazards models, the relative risk (RR) for bladder cancer was 1.15 (95% confidence interval (CI)=0.86-1.55) for individuals in the highest (i.e., most acidic) versus the lowest (i.e., least acidic) NAE quintile (p=0.38). Among men who smoked for more than 45 years, there was a suggestion of increased risk with higher NAE levels (RR=1.72, 95% CI=0.96-3.10, p=0.08).These findings do not indicate that urine pH is a major risk factor for bladder cancer, although certain subsets of individuals may be at increased risk.

The effect of consumption of fruits, vegetables, and antioxidants on the incidence of gastric cancer is inconclusive. In this prospective cohort study, we report the association of dietary intake of fruits, vegetables, antioxidants, and baseline serum levels of antioxidants with subsequent incidence of gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Participants of this study were 29,133 male smokers recruited into the α-Tocopherol, β-Carotene Cancer Prevention study between 1985 and 1988. At baseline, a self-administered food use questionnaire with 276 food items was used to assess dietary intake. Baseline serum samples were stored at −70°C. During a median follow-up of 12 years, 243 incident gastric adenocarcinomas (64 GCC and 179 GNCC) were diagnosed in this cohort, of whom 220 (57 GCC and 163 GNCC) had complete dietary information. For GCC, high dietary intake of retinol was protective [hazard ratio (HR), 0.46; 95% confidence interval (95% CI), 0.27-0.78], but high intake of α-tocopherol (HR, 2.06; 95% CI, 1.20-3.54) and γ-tocopherol (HR, 1.94; 95% CI, 1.13-3.34) increased risk. For GNCC, higher intakes of fruits (HR, 0.51; 95% CI, 0.37-0.71), vitamin C (HR, 0.60; 95% CI, 0.41-0.86), α-tocopherol (HR, 0.78; 95% CI, 0.55-1.10), γ-tocopherol (HR, 0.69; 95% CI, 0.49-0.96), and lycopene (HR, 0.67; 95% CI, 0.47-0.95) were protective. Our results suggest a difference in the effect of some of these exposures on GCC and GNCC. Tocopherols were associated with higher risk of GCC, whereas dietary intake of fruits, vitamin C, tocopherols, and lycopene seemed protective for GNCC.

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. We examined baseline serum concentrations of alpha-tocopherol and gamma-tocopherol to compare their respective associations with prostate cancer risk. From the ATBC Study cohort of 29 133 Finnish men, 50-69 years old, we randomly selected 100 incident prostate cancer case patients and matched 200 control subjects. Odds ratios and 95% confidence intervals (CIs) were estimated for the serum tocopherols (measured by high-performance liquid chromatography) using logistic regression models. All P values were two-sided. Odds ratios for the highest versus the lowest tertiles were 0.49 (95% CI = 0.24 to 1.01, P(trend) = .05) for alpha-tocopherol and 0.57 (95% CI = 0.31 to 1.06, P(trend) = .08) for gamma-tocopherol. Further analyses indicated that the association of high serum tocopherols with low prostate cancer risk was stronger in the alpha-tocopherol-supplemented group than in those not receiving alpha-tocopherol. Participants with higher circulating concentrations of the major vitamin E fractions, alpha-tocopherol and gamma-tocopherol, had similarly lower prostate cancer risk.

Background: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. Objective: We studied the relation between the intake of antioxidant vitamins and CHD risk. Design: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline. Results: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P = 0.17) and 1.23 (1.04, 1.45; P = 0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend < 0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. Conclusions: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.

At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (

In many observational studies, a higher intake of individual antioxidants is inversely associated with lung cancer risk. Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients; therefore, consideration of multiple antioxidants simultaneously may be important in terms of risk estimation. The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline (1985-1988), 27,111 Finnish male smokers aged 50-69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985-1999). Principal components analyses were individually applied to the carotenoid, flavonoid, and vitamin E nutrient groups, and summation of retained principal component scores, plus selenium and vitamin C, yielded the composite antioxidant index. In multivariate proportional hazards models, the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 (referent), 1.00 (95% confidence interval (CI): 0.87, 1.14), 0.91 (95% CI: 0.79, 1.05), 0.79 (95% CI: 0.68, 0.92), and 0.84 (95% CI: 0.72, 0.98) (p for trend = 0.002). These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers.

Background Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis. Study objective To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial. Design and setting The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 × 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed. Participants ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline. Main outcome measure The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases). Results Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had β-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (≥ 21 years; n = 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (RR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89). Conclusions Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation.

Background: An analysis of dietary patterns or combinations of foods may provide insight regarding the influence of diet on the risk of colon and rectal cancer. Objective: A primary aim of the Dietary Patterns and Cancer (DIETSCAN) Project was to develop and apply a common methodologic approach to study dietary patterns and cancer in 4 European cohorts: the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (Finland-ATBC), the Netherlands Cohort Study (NLCS) on Diet and Cancer, the Swedish Mammography Cohort (SMC), and the Ormoni e Dieta nella Eziologia dei Tumori (Italy-ORDET). Three cohorts (ATBC, NLCS, and SMC) provided data on colon and rectal cancer for the present study. Design: The cohorts were established between 1985 and 1992; follow-up data were obtained from national cancer registries. The participants completed validated semiquantitative food-frequency questionnaires at baseline. Results: Exploratory factor analysis, conducted within each cohort, identified 3-5 stable dietary patterns. Two dietary patterns - Vegetables and Pork, Processed Meats, Potatoes (PPP) - were common across all cohorts. After adjustment for potential confounders, PPP was associated with an increased risk of colon cancer in the SMC women (quintile4multivariate relative risk: 1.62; 95% CI: 1.12,2.34; P for trend = 0.01). PPP was also associated with an increased risk of rectal cancer in the ATBC men (quintile 4multivariate relative risk: 2.21; 95% CI: 1.07, 4.57; P for trend = 0.05). Neither pattern was associated with the risk of colon or rectal cancer in the NLCS women and men. Conclusion: Although certain dietary patterns may be consistent across European countries, associations between these dietary patterns and the risk of colon and rectal cancer are not conclusive. © 2004 American Society for Clinical Nutrition.

Intervention trials with supplemental β-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7–16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. β-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87–1.11; highest versus lowest quintile). The RRs for α-carotene, lutein/zeaxanthin, and lycopene were also close to unity. β-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67–0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in β-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

Diet may affect mood and cognitive functions. Tryptophan and serine augmentation strategies have been applied for patients with mood or psychotic disorders. We studied the association between dietary intake of amino acids and low mood. We studied 29,133 men aged 50-69 years for 5-8 years in a population-based trial in Finland. Intake of amino acids was calculated from a diet history questionnaire completed by 27,111 men at baseline. Self-reports of depressed mood were recorded thrice a year, data on hospital treatment due to depressive disorders were derived from the national Hospital Discharge Register, and suicides were identified from death certificates. Participants were smokers at study entry. Strengths of our study include detailed data on food consumption, a substantial number of study participants, a long prospective follow-up time, and versatile data on indices of low mood. We found no association between the dietary intake of amino acids and self-report of depressed mood or risk of suicide. However, dietary intake of lysine and serine was associated with risk of hospital treatment due to major depressive disorder but these associations disappeared after excluding from analysis those who had reported depressed mood at study entry. There is no consistent association between dietary intake of amino acids and low mood.

Background: Poor dental health has been associated with increased risks of oral, esophageal, and gastric cancer and may also be associated with pancreatic cancer. In addition, Helicobacter pylori has been found in dental plaque and has been associated with periodontal disease and pancreatic cancer. Objective: The objective was to investigate prospectively the relation between dentition history and pancreatic cancer in the AlphaTocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland and the association between dentition history and H. pylori seropositivity in a cross-sectional sample of subjects without cancer (n = 475) from the same cohort. Design: Of the 29 104 male smokers aged 50‐69 y in the cohort for whom there were complete data, 174 developed pancreatic cancer from 1985 to 1997. Cox proportional hazard models were used to estimate age-, smoking-, education-, urban living‐, and height-adjusted hazard ratios and 95% CIs for pancreatic cancer, and logistic regression models were used to estimate age- and education-adjusted odds ratios for H. pylori carriage. Results: Tooth loss was positively associated with pancreatic cancer (edentulous compared with missing 0‐10 teeth: hazard ratio = 1.63; 95% CI: 1.09, 2.46; P for trend = 0.02) but was not significantly associated with H. pylori seropositivity (edentulous compared with missing 0‐10 teeth: odds ratio = 1.30; 95% CI: 0.73, 2.32; P for trend = 0.37). Conclusion: Additional studies are needed to evaluate the association between tooth loss and pancreatic cancer, as well as cancers at other gastrointestinal sites, particularly with respect to possible biological mechanisms. Am J Clin Nutr 2003;78:176‐81.

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori-positive atrophic corpus gastritis. Duration of endoscopic follow-up was 6 years and follow-up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow-up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fisher's exact test). There was a small but significant (p=0.0004, Page's test) declining trend in mean atrophy score of the corpus during follow-up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow-up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

Background and Purpose— Homocysteine is associated with stroke, but it is not clear whether this relationship is causal. We examined the association between total serum homocysteine concentration (tHcy) and cerebral infarction in a cohort of Finnish male smokers. Methods— This is a matched case-control study of 201 cases of cerebral infarction and 201 concurrently sampled age-matched controls nested in a cohort of 13 840 male smokers free of cardiovascular disease at the completion of the Alpha-Tocopherol and Beta-Carotene (ATBC) Cancer Prevention study. Conditional logistic regression was used to calculate odds ratios (ORs) and to adjust for confounding variables. An unmatched analysis was also performed. Results— The geometric mean tHcy was 13.3 μmol/L (95% CI, 12.6 to 13.9) in cases and 12.6 μmol/L (95% CI, 12.0 to 13.2) in controls ( P =0.09). There was a graded increase in the OR of cerebral infarction per quartile increase in tHcy (OR, 1.0, 1.7, 1.9, 2.1; trend P =0.02; 201 case-control pairs) when adjusted for traditional risk factors. There was a similar trend in a subgroup of 120 case-control pairs for which further adjustment for lifestyle factors was possible (OR, 1.0, 1.9, 2.5, 2.2; trend P =0.07 in the matched analyses; OR, 1.0, 1.2, 1.9, 2.0; trend P =0.02 in the unmatched analyses). The adjusted OR per 1-SD increase in log-transformed tHcy (equivalent to 4.7 μmol) was 1.4 (95% CI, 1.1 to 1.7; P =0.01). Conclusions— tHcy appears to predict cerebral infarction in Finnish male smokers.

The objective of this study was to investigate the association between flavonol and flavone intake and the risk of intermittent claudication in male smokers. The study population consisted of participants of the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study, who were free of intermittent claudication at study entry. These 25,041 male smokers were 50-69 years old at baseline. Participants completed a validated dietary questionnaire at baseline. The occurrence of intermittent claudication was assessed by annual administration of the Rose questionnaire. During the median follow-up of 4.1 years, 2412 new cases of intermittent claudication were observed. Dietary intake of flavonols and flavones was inversely associated with the risk of intermittent claudication when adjusted for cardiovascular risk factors (relative risk, RR in the highest vs. lowest quintile of intake 0.86, 95% confidence interval, CI: 0.75-0.98, p for trend 0.007). However, after further adjustment for intakes of vitamins C and E and total carotenoids, the association was attenuated (RR: 0.93, 95% CI: 0.81-1.08, p for trend 0.12). The risk of intermittent claudication was lower among men in the highest quintile of vegetable consumption (RR: 0.78, 95% CI: 0.69-0.89, p for trend 0.0001) and among wine drinkers (RR: 0.63, 95% CI: 0.41-0.98). Adjustment for flavonol and flavone intake only marginally changed these associations. In conclusion, flavonol and flavone intake was not independently associated with the risk of intermittent claudication.

Associations between lung cancer risk and common polymorphisms in the DNA repair genes xeroderma pigmentosum complementation group D (XPD), X-ray repair cross-complementing group 1 (XRCC1), XRCC3 and apurinic/apyrimidinic endonuclease/redox factor 1 were examined within a randomized clinical trial designed to determine whether alpha-tocopherol, beta-carotene, or both would reduce cancer incidence among male smokers in Finland. We found no direct association between lung cancer risk and any of the DNA repair genotypes studied, however, the association between XPD codon 751 genotype and lung cancer was modified by alpha-tocopherol supplementation, and the association between XRCC1 codon 399 genotype and lung cancer was modified by the amount of smoking. Our results suggest that common alterations in single DNA repair genes are not major determinants of lung cancer susceptibility among smokers.

Objective: Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation (α-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. Methods: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. Results: Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96–3.08, p = 0.07). Supplementation with α-tocopherol had no impact on the MnSOD–prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15–6.40, p = 0.02). Conclusion: These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued.

Few studies have examined exercise in relation to risk of renal cell cancer. We examined the association between leisure-time and occupational physical activity and renal cell cancer in a cohort of 29,133 male smokers 50–69 years of age in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study. Physical activity was assessed at baseline using a self-administered questionnaire that inquired about usual level of physical activity during leisure-time and at work during the past year. Cox proportional hazards modeling was used to adjust simultaneously for known or suspected risk factors for renal cell cancer. During 12 years (354,407 person-years) of follow-up, 210 incident cases of renal cell cancer were identified. In age-adjusted analysis, the RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy) were 1.0, 0.89 (95% CI = 0.67–1.17) and 0.38 (95% CI = 0.15–0.94), respectively (p-value for trend = 0.06). After adjustment for body mass index, energy intake, smoking, hypertension, education and fruit and vegetable intake, the multivariate RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy), were 1.0, 0.89 (95% CI = 0.66–1.19), and 0.46 (95% CI = 0.18–1.13) (p-value for trend = 0.12). Occupational physical activity was unrelated to renal cell cancer risk. These data suggest that recreational physical activity may play a role in the prevention of renal cell cancer in men. © 2003 Wiley-Liss, Inc.

Objective To characterize novel type of mutations of the epithelial sodium channel (ENaC) β or γ subunits in patients with Liddle's syndrome, an autosomal dominant form of hypertension.Patients and methods DNA samples from two probands with early-onset, treatment-resistant hypertension and suppresse

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 α-tocopherol (50 mg/day), β-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, α-or γ-tocopherol, retinol, α- or β-carotene, lycopene or lutein+zeaxanthin and risk for colorectal cancer. Serum α-tocopherol, β-carotene or retinol was also not associated with the risk, neither did the season when baseline blood was drawn modify the relationship between serum β-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).

There have been few prospective studies relating diet to pancreatic cancer, with most having fewer than 100 cases and only one examining dietary nutrients. The authors prospectively examined dietary factors hypothesized to be associated with exocrine pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland. Of the 27,111 male smokers aged 50-69 years with complete dietary information, as ascertained from a self-administered dietary history questionnaire given at baseline (1985-1988), 163 developed pancreatic cancer from 1985 through November 1997. Cox proportional hazards models were used to estimate smoking- and age-adjusted hazard ratios and 95% confidence intervals. Energy-adjusted butter consumption and saturated fat intake were positively associated with pancreatic cancer (highest quintile vs. lowest: hazard ratio (HR) = 1.40, 95% confidence interval (CI): 0.87, 2.25 (p trend = 0.04), and HR = 1.60, 95% CI: 0.96, 2.64 (p trend = 0.02), respectively). Energy intake and energy-adjusted carbohydrate intake were inversely associated with the disease (highest quintile vs. lowest: HR = 0.62, 95% CI: 0.36, 1.07 (p trend = 0.05), and HR = 0.62, 95% CI: 0.37, 1.03 (p trend = 0.02), respectively). These results support the hypothesis that a high intake of saturated fat may increase the risk of pancreatic cancer in smokers, while greater intakes of energy and carbohydrate may reduce the risk.

We examined the association between physical activity and lung cancer in a prospective cohort of 27,087 male smokers, ages 50-69 years, enrolled in the Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) Study. After an average of 10 years of follow-up, 1,442 lung cancer cases were diagnosed. Cox proportional hazards models were used to estimate the relative risk (RR) and 95% confidence intervals (CI) of lung cancer associated with self-reported occupational and leisure-time activity, adjusted for age, supplement group, body mass index, cigarettes smoked daily, years of smoking, education, energy intake and vegetable intake. There were no associations between occupational, leisure-time or combined categories of physical activity with lung cancer risk; however, age appeared to modify the effect of leisure-time activity (p = 0.02). Within increasing quartiles of age, the RRs (CI) for men active in leisure time compared to sedentary men were 0.77 (0.54-1.09), 0.74 (0.57-0.95), 1.09 (0.89-1.33) and 1.03 (0.88-1.21). These data suggest that among smokers, neither occupational nor leisure-time activity is associated with lung cancer risk. There may, however, be some modest risk reduction associated with leisure activity among younger smokers. Published 2002 Wiley-Liss, Inc.

Background: The objective of this investigation was to evaluate the association between toenail selenium concentration and lung cancer risk in male smokers. Methods: We conducted a nested case–control study within the Alpha–Tocopherol Beta–Carotene Cancer Prevention Study cohort. This substudy included 250 randomly selected incident lung cancer cases and 250 controls matched on age (up to ± 5 years), intervention group assignment, and date or randomization (±15 days). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression methods. Finland began fortification of argricultural fertilizers in the fall of 1984, increasing the dietary intake, plasma, and toenail selenium concentrations for the population. The present analyses were based on the calculated residual of toenail selenium after regressing it on date of randomization. The selenium residual and the interaction of the residual with date of randomization were included in models with smoking status and body mass index as covariates. Results: We observed a suggestion of a protective association for higher selenium status among men who entered the trial early (when the range of selenium values included very low levels). The OR for men with adjusted toenail selenium concentrations at the 75th percentile compared to those with the lowest selenium concentrations ranged between 0.20 (0.09–0.44) for men randomized earliest in the trail and 0.61 (0.27–1.41) for men randomized in the fifth year. Conclusions: These results suggest that low selenium status may be associated with increased risk for lung cancer.

Objectives: This study investigated the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of gastric cancer. Methods: A total of 29,133 male smokers, aged 50–69 years, participated in a placebo-controlled prevention trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in southwestern Finland between 1985 and 1993. The men were randomly assigned to receive alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) supplementation in a 2 × 2 factorial design. We identified 126 gastric cancer cases during the median follow-up of six years. Of these, 122 were adenocarcinomas: 75 of intestinal type, 30 of diffuse type, and 17 of mixed type. Results: There was no significant effect for either supplementation on the overall incidence of gastric cancer: relative risk (RR) 1.21, 95% confidence interval (CI) 0.85–1.74 for alpha-tocopherol, and RR 1.26, 95% CI 0.88–1.80 for beta-carotene. Subgroup analyses by histologic type suggested an increased risk for beta-carotene on intestinal type cancers, RR 1.59, 95% CI 0.99–2.56. There were no differences across anatomic locations (cardia/noncardia) in the effects of alpha-tocopherol or beta-carotene supplementation. Conclusions: Our study found no overall preventive effect of long-term supplementation with alpha-tocopherol or beta-carotene on gastric cancer in middle-aged male smokers.

Objective: To examine the association between several medical conditions, anthropometric measurements, occupational and leisure physical activity, and pancreatic cancer in a cohort of male Finnish smokers. Methods: We performed a cohort analysis of the 172 subjects who developed pancreatic cancer between 1985 and 1997 (median 10.2 years follow-up) among the 29,048 male smokers, 50–69 years old, who had complete baseline data and participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: We observed positive associations between pancreatic cancer risk and self-reported history of diabetes mellitus (HR = 2.02, 95% CI 1.17–3.50) and bronchial asthma (HR = 2.16, 95% CI 1.17–3.98). Men having combined occupational and leisure activity greater than at sedentary levels had reduced risk for the cancer; for example those with moderate/heavy activity in both settings showed a HR of 0.42 (95% CI 0.22–0.83). There were no significant associations with other self-reported illnesses, total or HDL (high-density lipoprotein) cholesterol, height, weight, or body mass index. Conclusions: Our data suggest that diabetes mellitus and bronchial asthma predict the subsequent risk of developing pancreatic cancer in male smokers, and that greater physical activity may reduce the risk.

We evaluated the accuracy and time to reporting of cancer diagnoses obtained through the Finnish Cancer Registry (FCR) for the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study in 1985-1997. In the ATBC Study suspect neoplasms were centrally reviewed through medical records and pathology specimens. The FCR data were compared against the reviewed data for 3600 cancers of eight sites. For most sites, 95% of the cases were reported to the FCR within 0.9 years with longer delays for lung and pancreatic cancers. Ninety-six percent of all FCR cases received the same primary site diagnosis in the ATBC review, and in 1.4% no malignancy was found. Conversely, 97% of cancers ascertained in the ATBC review had the same primary site in the FCR and 0.8% were unknown to the Registry. The accuracy of the FCR data is high but the delay in case notification should be considered in epidemiological studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and icecream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

The intake of the mainly plant-derived n-3 PUFA α-linolenic acid (ALA) has been reported to be associated with a lower risk of CHD. However, the results have been inconsistent. Therefore, the objective of the present study was to examine the association between the intake of ALA and the risk of CHD. Potential effect modification by the intake of long-chain n-3 PUFA (n-3 LCPUFA) was also investigated. Data from eight American and European prospective cohort studies including 148 675 women and 80 368 men were used. The outcome measure was incident CHD (CHD event and death). During 4–10 years of follow-up, 4493 CHD events and 1751 CHD deaths occurred. Among men, an inverse association (not significant) between the intake of ALA and the risk of CHD events and deaths was observed. For each additional gram of ALA consumed, a 15 % lower risk of CHD events (hazard ratios (HR) 0·85, 95 % CI 0·72, 1·01) and a 23 % lower risk of CHD deaths (HR 0·77, 95 % CI 0·58, 1·01) were observed. No consistent association was observed among women. No effect modification by the intake of n-3 LCPUFA was observed.

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10 '21), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10 '10), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10 '8) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10 '13 and 3.63 × 10 '11, respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL. © 2014 Nature America, Inc. All rights reserved.

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.

The authors examined prospectively whether dietary folate and other factors known to influence methyl-group availability were associated with the development of exocrine pancreatic cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Of the 27,101 healthy male smokers aged 50--69 years who completed a self-administered dietary questionnaire at baseline, 157 developed pancreatic cancer during up to 13 years of follow-up from 1985 to 1997. Cox proportional hazards models were used to estimate the hazards ratios and 95% confidence intervals. The adjusted hazards ratio comparing the highest with the lowest quintile of dietary folate intake was 0.52 (95% confidence interval: 0.31, 0.87; p-trend = 0.05). Dietary methionine, alcohol intake, and smoking history did not modify this relation. No significant associations were observed between dietary methionine, vitamins B(6) and B(12), or alcohol intake and pancreatic cancer risk. Consistent with prior studies, this study shows that cigarette smoking was associated with an increased risk (highest compared with lowest quintile, cigarettes per day: hazards ratio = 1.82; 95% confidence interval: 1.10, 3.03; p-trend = 0.05). These results support the hypothesis that dietary folate intake is inversely associated with the risk of pancreatic cancer and confirm the risk associated with greater cigarette smoking.

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B(6), vitamin B(12)) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B(12), or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B(6) levels. Compared with men with the lowest vitamin B(6) concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B(6) in lung cancer.

In order to examine whether a polymorphism in the promoter region of the myeloperoxidase (MPO) gene is associated with lung cancer among male smokers, we conducted a case-control study nested within a Finnish clinical trial cohort. Although we found no evidence of an overall association between lung cancer risk and MPO genotype, the variant MPO genotype was associated with an increased risk of lung cancer among a subset of older men. These findings contrast with those from previous studies that report decreased lung cancer risk among MPO variant individuals.

Background α-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 α-tocopherol modified serum hormone levels. Methods Men who were cancer-free consumed ≥ 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 α-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 α-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 α-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 α-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 α-tocopherol and placebo were 539 (CI, 517–562) and 573 (CI, 549–598) ng/dl, respectively. Conclusions These results suggest that long-term α-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 α-tocopherol treatment group of the ATBC Study. Prostate 46:33–38, 2001. © 2001 Wiley-Liss, Inc.

Objective: To study the associations between the intake of flavonols and flavones and the risk of cancer.

Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile [ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7-2.5), 1.1 (0.6-2.2) and 2.4 (1.1-5.1); P(trend) = 0.008]. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.

Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2-Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2-Q4 vs. Q1 OR = 1.48, 95% CI: 1.00-2.20) and statistically significant among male smokers (Q2-Q4 vs. Q1 OR = 1.83, 95% CI: 1.14-2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2-Q4 vs. Q1: OR = 2.31, 95% CI: 1.62-3.30) and a highly significant trend was observed (P = 8.7 × 10(-7)). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52-2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers.

Background and Purpose —Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke. Methods —The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers. Results —During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of β-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0.91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between β-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99). Conclusions —Dietary intake of β-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.

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.