Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland.

BACKGROUND: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types). METHODS: We used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction. RESULTS: Among vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74-83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant. In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8-52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD. CONCLUSION: Overall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained.

Coffee and tea consumption and risk of stroke subtypes in male smokers.

BACKGROUND AND PURPOSE: Coffee and tea consumption could potentially reduce the risk of stroke because these beverages have antioxidant properties, and coffee may improve insulin sensitivity. We examined the associations of coffee and tea consumption with risk of stroke subtypes. METHODS: We used prospective data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort study of 26 556 male Finnish smokers aged 50 to 69 years without a history of stroke at baseline. Coffee and tea consumption was assessed at baseline using a validated food-frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through December 2004, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained from national registries. RESULTS: After adjustment for age and cardiovascular risk factors, both consumption of coffee and tea was statistically significantly inversely associated with the risk of cerebral infarction but not intracerebral or subarachnoid hemorrhage. The multivariate relative risk of cerebral infarction for men in the highest category of coffee consumption (>/=8 cups/d) was 0.77 (95% CI, 0.66 to 0.90; P for trend <0.001) compared with those in the lowest category (<2 cups/d). The corresponding relative risk comparing men in the highest category of tea consumption (>/=2 cups/d) with those in the lowest category (nondrinkers) was 0.79 (95% CI, 0.68 to 0.92; P for trend=0.002). CONCLUSIONS: These results suggest that high consumption of coffee and tea may reduce the risk of cerebral infarction among men, independent of known cardiovascular risk factors.

Serum enterolactone concentration and the risk of coronary heart disease in a case-cohort study of Finnish male smokers.

The lignan enterolactone produced by the intestinal microflora from dietary precursors has been hypothesized to protect against coronary heart disease. The present study examined the association between serum enterolactone concentration and the risk of coronary heart disease. A prospective case-cohort study was conducted among male smokers randomized to receive a placebo supplement in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1986-1999). Serum enterolactone concentrations were measured by the gas chromatography-mass spectrometry method in serum collected at trial baseline from 340 men diagnosed with nonfatal myocardial infarction (n = 205) or coronary death (n = 135) during follow-up and from the randomly selected subcohort of 420 subjects. The classic risk factors-adjusted rate ratios for all coronary heart disease events in increasing quintiles of enterolactone were 1.00 (referent), 0.85 (95% confidence interval (CI): 0.51, 1.43), 0.59 (95% CI: 0.35, 1.00), 0.69 (95% CI: 0.40, 1.16), and 0.63 (95% CI: 0.33, 1.11), and the p(trend) was 0.07. For the highest versus the lowest quintile of enterolactone, the rate ratios for nonfatal myocardial infarction and coronary death were 0.67 (95% CI: 0.37, 1.23; p(trend) = 0.10) and 0.57 (95% CI: 0.26, 1.25; p(trend) = 0.18), respectively. In conclusion, only weak support for the association between serum enterolactone concentration and coronary heart disease was found.

Dietary patterns associated with colon and rectal cancer: results from the Dietary Patterns and Cancer (DIETSCAN) Project.

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 (quintile 4(multivariate) 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 4(multivariate) 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.

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.

BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. METHODS: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (P(trend)<.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) =.02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (P(trend)<.001) and rectum (P(trend) =.02). CONCLUSION: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer.

Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study.

AIMS: To evaluate the 6-year post-trial effects of alpha-tocopherol and beta-carotene supplementation on coronary heart disease (CHD) in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. METHODS AND RESULTS: 29,133 male smokers, aged 50-69 years were randomised to receive alpha-tocopherol 50 mg, or beta-carotene 20 mg, or both, or placebo daily for 5-8 years. At the beginning of the post-trial follow-up, 23,144 men were still at risk for a first-ever major coronary event (MCE), and 1255 men with pre-trial history of myocardial infarction (MI) were at risk for MCE. Post-trial risk for MCE (n=2059) was 0.95 (95% confidence interval 0.87-1.04) among alpha-tocopherol recipients compared with non-recipients, and 1.14 (1.04-1.24) among beta-carotene recipients compared with non-recipients. The risk for non-fatal MI (n=993) was 0.96 (0.85-1.09) and 1.16 (1.03-1.32), and for fatal CHD (n=1066) 0.94 (0.83-1.06) and 1.11 (0.99-1.25), respectively. Among men with pre-trial MI no effects were observed in post-trial risk of MCE (n=257). CONCLUSION: beta-Carotene seemed to increase the post-trial risk of first-ever non-fatal MI but there is no plausible mechanism to support it. Our findings do not advocate the use of alpha-tocopherol or beta-carotene supplements in prevention of CHD among male smokers.

Postintervention effect of alpha tocopherol and beta carotene on different strokes: a 6-year follow-up of the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

BACKGROUND AND PURPOSE: In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, -25% to -1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes. METHODS: A total of 29,133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes. RESULTS: Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively. CONCLUSIONS: Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.

Fatty acids and risk of prostate cancer in a nested case-control study in male smokers.

There is some evidence that alpha-linolenic acid might be positively related to prostate cancer risk. Associations between serum fatty acid composition as well as fatty acid intakes and prostate cancer risk were examined in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133 male smokers aged 50-69 years. During 5-8 years of follow-up, 246 prostate cancer cases were diagnosed. One control was selected and matched by age (+/- 1 month) for each case from the cohort subjects alive and free of prostate cancer at the time the case was diagnosed. This study included 198 case-control pairs with baseline serum sample available for both. Fatty acids of serum cholesterol esters were measured as a percentage of total fatty acids, using capillary gas chromatography. Intakes of fatty acids were assessed from a validated self-administered dietary questionnaire. Serum and dietary fatty acids had no consistent association with prostate cancer risk. Serum alpha-linolenic acid was not related to prostate cancer risk. Twofold risk was found in the highest quartile of serum myristic acid compared with the lowest quartile (odds ratio, 1.93; 95% confidence interval, 1.02-3.64). alpha-Tocopherol supplementation modified the association between serum linoleic acid and prostate cancer risk (P for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04-0.68) in the highest quartile of serum linoleic acid compared with the lowest quartile in men who received alpha-tocopherol, whereas no association was found in men who did not receive alpha-tocopherol. In conclusion, we found no overall association between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with alpha-tocopherol. High serum myristic acid associated with an increased risk of prostate cancer.

Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up.

CONTEXT: In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants. OBJECTIVE: To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review. MAIN OUTCOME MEASURES: Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality. RESULTS: Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases. CONCLUSIONS: The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.

Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland).

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 x 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% Cl 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.