Perspectives of an NCI T32 Training Program Designed to Train a Diverse Workforce in Cancer Health Equity Research.

With cancer health disparities on the rise in the United States (USA), there is an increased need for novel approaches to address these challenges. One such approach that may help address these disparities is increasing diversity in the biomedical research workforce. The Cancer Health Equity and Career Development Program (CHECDP) embodies this approach by recruiting and training underrepresented minorities in cancer research to develop the skills and training needed to be competitive for independent research careers, thus diversifying the biomedical research workforce. The training model that CHECDP employs is unique with its funding through the NCI training mechanism, its strong institutional support, and its participant-driven curriculum. The curriculum includes educational, career, and leadership opportunities that are continuously evaluated for sustained impact. The program has been comprised of mostly under-represented minorities that have been propelled to independent careers with a high rate of funded career development awards. Our T32 program serves as a model of success for other programs seeking to diversify the biomedical research workforce and reduce cancer health disparities.

Construction and case study of a novel lung cancer risk index.

PURPOSE: This study constructs a lung cancer risk index (LCRI) that incorporates many modifiable risk factors using an easily reproducible and adaptable method that relies on publicly available data. METHODS: We used meta-analysis followed by Analytic Hierarchy Process (AHP) to generate a lung cancer risk index (LCRI) that incorporates seven modifiable risk factors (active smoking, indoor air pollution, occupational exposure, alcohol consumption, secondhand smoke exposure, outdoor air pollution, and radon exposure) for lung cancer. Using county-level population data, we then performed a case study in which we tailored the LCRI for use in the state of Illinois (LCRIIL). RESULTS: For both the LCRI and the LCRIIL, active smoking had the highest weights (46.1% and 70%, respectively), whereas radon had the lowest weights (3.0% and 5.7%, respectively). The weights for alcohol consumption were 7.8% and 14.7% for the LCRI and the LCRIIL, respectively, and were 3.8% and 0.95% for outdoor air pollution. Three variables were only included in the LCRI: indoor air pollution (18.5%), occupational exposure (13.2%), and secondhand smoke exposure (7.6%). The Consistency Ratio (CR) was well below the 0.1 cut point. The LCRIIL was moderate though significantly correlated with age-adjusted lung cancer incidence (r = 0.449, P < 0.05) and mortality rates (r = 0.495, P < 0.05). CONCLUSION: This study presents an index that incorporates multiple modifiable risk factors for lung cancer into one composite score. Since the LCRI allows data comprising the composite score to vary based on the location of interest, this measurement tool can be used for any geographic location where population-based data for individual risk factors exist. Researchers, policymakers, and public health professionals may utilize this framework to determine areas that are most in need of lung cancer-related interventions and resources.

Creation and Evaluation of the Illinois Cancer Risk Index as a Predictor of Four Common Cancers.

INTRODUCTION: Nearly half of all cancer deaths in the US are attributed to 4 common cancers: lung, colorectal, breast, and prostate. Illinois residents experience higher rates of cancer death from all 4 cancers compared with the US overall. We developed the Illinois Cancer Risk Index (ICRI), which incorporates many predictors of these cancers into a single summary measure, to identify Illinois counties that would benefit most from public health intervention. METHODS: We identified 90 county-level predictors of 4 common cancers, used multicollinearity testing to reduce this number to 61, and applied factor analysis to extract and analyze 4 factors representing 25 variables. Next, we created the ICRI by regressing the 4 factors on our outcome of interest - an age-adjusted common cancers mortality rate (CCMR), incorporating the direction of the ß-coefficients from regression models to sum factor scores. Finally, we mapped and assessed the geographic distributions of both ICRI and CCMR by county across the state. RESULTS: The ICRI was positively associated with the CCMR (r = 0.59, P < .001) and explained 32.2% of the variance in the CCMR across Illinois. The ICRI showed distinct geospatial patterns across the state, with the highest risk counties located in the east-central, far northern, and southern regions. The CCMR showed similar geospatial patterns. CONCLUSION: Our study identifies counties in Illinois that may benefit most from interventions that target multiple cancer risk factors simultaneously. The ICRI may be adapted for use in other geographic locations where data are available.

Equity in Cancer and Chronic Disease Prevention through a Multi-Pronged Network Intervention: Works-in-Progress.

The increasing rates of cancer incidence are disproportionately borne by populations that are ineligible for screening and historically marginalized populations. To address this need, our community-centered model seeks to catalyze the widespread diffusion of evidence-based information and resources (e.g., community-based organizations, federally qualified health centers) to reduce the risks of cancer, chronic disease, and other conditions. In this study, we tested whether improving personal health literacy (i.e., confidence in seeking information) and enabling successful information transfer (i.e., intention to share the specific information learned through the program) among community residents could contribute to greater diffusion intention (i.e., number of network members with whom residents plan to share information and resources). The current study used post-intervention surveys, which were administered to Chicago residents who were 18 years or older and had participated in the program. Among the 1499 diverse Chicago residents, improved personal health literacy was associated with greater diffusion intention (ORs = 2.00-2.68, 95% CI [1.27-4.39], p ≤ 0.003). Successful information transfer was associated with greater diffusion, especially for cancer and other chronic disease risk reductions (ORs = 3.43-3.73, 95% CI [1.95-6.68], p < 0.001). The findings highlight the potential gains for health equity through sustainable, scalable, multi-sectoral partnerships.

Outcome of BMI2+: Motivational Interviewing to Reduce BMI Through Primary Care AAP PROS Practices.

BACKGROUND: Pediatric obesity rates in the United States remain at an all-time high. Pediatric primary care clinicians and registered dietitians can help treat childhood obesity, and motivational interviewing (MI) has shown promising effects in prior trials. METHODS: We randomized 18 pediatric primary care practices to receive the Brief Motivational Interviewing to Reduce BMI or BMI2+ intervention or continue with usual care (UC). Practices were recruited through the American Academy of Pediatrics Pediatric Research in Office Settings network. The intervention comprised 4 components1: in-person and telehealth MI counseling by pediatric clinicians; 4 recommended sessions,2 6 telephone MI counseling sessions from a registered dietitian,3 text message reminders and tailored motivational messages, and4 parent educational materials. The main outcome was the change in the percentage of the 95th percentile of BMI. The study was conducted 2017 through 2021. RESULTS: There was a significant treatment x time interaction (b = 0.017, 95% confidence interval: [0.0066-0.027]) for the main outcome, favoring the UC group, with youth in the intervention arm showing a greater relative increase in their percent of the 95th percentile. CONCLUSIONS: There was no overall benefit of the intervention and, contrary to expectations, youth in the intervention arm gained more weight, based on percent of the distance from the 95th percentile than matched youth from UC practices. The absolute excess weight gain among intervention relative to UC youth was small, approximately 0.5 BMI units and 1 kg over 2 years. We offer several potential explanations for these unexpected findings.

Phytanic acid and the risk of non-Hodgkin lymphoma.

Greater consumption of red meat, processed meat and dairy products has been associated with an increased risk of non-Hodgkin lymphoma (NHL) in several previous reports. Phytanic acid, a saturated fatty acid obtained primarily through the consumption of ruminant meat and dairy products, may offer a potential underlying mechanism for these associations. In a population-based case-control study of 336 cases and 460 controls conducted in Nebraska during 1999-2002, we examined whether phytanic acid-containing foods or total phytanic acid intake, estimated from a food frequency questionnaire and the published phytanic acid values of 151 food items, were associated with increased NHL risk. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for overall NHL and the common NHL histologic subtypes. In multivariable models, higher intakes of density-adjusted beef [OR(T3 vs. T1) = 1.5 (1.1-2.2); P(trend) = 0.02], total dairy products [OR = 1.5 (1.1-2.2); P(trend) = 0.02) and milk [OR = 1.6 (1.1-2.3); P(trend) = 0.01] were associated with an increased risk of NHL. Intake of total phytanic acid was positively associated with NHL risk [OR = 1.5 (1.0-2.1); P(trend) = 0.04]. In analyses stratified by NHL subtype, greater consumption of beef was associated with an increased risk of diffuse large B-cell lymphoma, and greater consumption of milk was associated with an increased risk of follicular lymphoma (FL). Total phytanic acid intake was associated with an increased risk of FL and small lymphocytic lymphoma/chronic lymphocytic leukemia. Our results provide support that total phytanic acid and phytanic acid-containing foods may increase NHL risk.

Genome-wide association study identifies common variants associated with circulating vitamin E levels.

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P= 1.7 × 10(-8)) and rs11057830 on 12q24.31 (P= 2.0 × 10(-8)) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P= 2.7 × 10(-10)). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P= 7.8 × 10(-12) (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 × 10(-10) (rs2108622 on 19pter-p13.11 near CYP4F2) and P= 8.2 × 10(-9) (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n= 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P< 1 × 10(-4) identified.

Estimated phytanic acid intake and prostate cancer risk: a prospective cohort study.

Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study--a cohort of Finnish male smokers aged 50-69 years. Diet was assessed at baseline in 27,111 participants using a validated 276-item dietary questionnaire. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items to estimate total daily intake. During up to 21 years of follow-up, a total of 1,929 incident prostate cancer cases (including 438 advanced cases) were identified. Higher phytanic acid intake, though unrelated to the risk of localized disease [relative risks (RR) and 95% confidence intervals (CI) for increasing quartiles of intake = 1.00 (ref), 0.83 (0.68-1.01), 0.76 (0.62-0.94) and 0.91 (0.74-1.13); p trend = 0.23], was associated with increased risks of advanced prostate cancer [RR and 95% CI = 1.00 (ref), 1.43 (1.09-1.89), 1.31 (0.99-1.75) and 1.38 (1.02-1.89); p trend = 0.06]. This association appeared to be driven predominantly by phytanic acid obtained from dairy products (particularly butter). Our study indicates that phytanic acid may contribute to previously observed associations between high-fat animal foods (particularly dairy products) and prostate cancer risk, although some caution is warranted as it may be acting as a surrogate marker of dairy fat.

Inverse association between glutathione peroxidase activity and both selenium-binding protein 1 levels and Gleason score in human prostate tissue.

BACKGROUND: Data from human epidemiological studies, cultured mammalian cells, and animal models have supported a potentially beneficial role of selenium (Se) in prostate cancer prevention. In addition, Se-containing proteins including members of the glutathione peroxidase (GPx) family and Selenium-Binding Protein 1 (SBP1) have been linked to either cancer risk or development. For example, SBP1 levels are typically reduced in tumors compared to non-cancerous tissue, with the degree of reduction associated with increasingly poor clinical outcome. METHODS: In order to investigate inter-relationships between blood and tissue Se levels and GPx activity, tissue SBP1 levels, and disease aggressiveness using the Gleason score, we measured levels of selenium and selected selenoproteins in fasting serum and histologically normal prostate tissues obtained from 24 men undergoing radical prostatectomy for the treatment of localized prostate cancer. RESULTS: GPx enzyme activity was inversely correlated with SBP1 levels in prostate tissue as determined by densitometry of Western blots obtained using anti-SBP1 antibodies [partial Spearman's correlation coefficients and corresponding P-values overall and in African-Americans = -0.42 (0.08) and -0.53 (0.10), respectively], which is consistent with previous observations in cultured cells and mice. Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02). CONCLUSION: These studies support the continued investigation of the role of Se and selenoproteins in prostate cancer prevention, development, and prognosis.

Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.

Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.

Mask Compliance Training for Individuals With Intellectual and Developmental Disabilities.

Since the arrival of the novel coronavirus, recommendations for public masking have emerged to decrease infection rates. For a variety of reasons, tolerating wearing a mask is challenging for many individuals with intellectual and developmental disabilities (IDDs). Therefore, we evaluated behavioral strategies to promote compliance with wearing a mask with six hospitalized individuals diagnosed with IDDs. One participant was compliant with wearing the mask for extended durations during baseline while engaging in various activities (e.g., academics, leisure). For the other five individuals, engagement in activities alone was ineffective. Blocking mask removal, reinforcement for mask wearing, and noncontingent access to preferred activities or competing stimuli were then evaluated using a changing-criterion design in which the duration participants were required to tolerate the mask gradually increased. Increases in compliance with mask wearing were achieved with all participants; however, the terminal duration was attained for only four of the five individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-021-00583-7.

No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma.

Previous epidemiologic studies that have examined the relationship between renal cell carcinoma (RCC) risk and intakes of plant foods and antioxidant nutrients have yielded inconsistent results. We therefore examined the associations between intakes of fruit, vegetables, carotenoids, flavonoids, vitamin E and vitamin C and RCC risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. At baseline, 27,062 male Finnish smokers aged 50-69 years completed a 276-item dietary questionnaire that included questions on frequency of consumption and portion size. During up to 19 years of follow-up, 255 men developed RCC. Cox proportional hazards models were utilized to estimate relative risks (RR) and 95% confidence intervals (CI). Despite a large range in intake, no association was observed between fruit, vegetables or antioxidant nutrients and RCC risk. For example, multivariate RRs and 95% CIs for the highest versus the lowest quartile of intake were 0.79 (0.55-1.14), 1.23 (0.85-1.79), 1.09 (0.74-1.60), 0.83 (0.57-1.21), 1.09 (0.73-1.64) and 0.99 (0.67-1.46) for fruit, vegetables, total carotenoids, total flavonoids, total vitamin E and vitamin C, respectively (all p values for trend > 0.05). Our results indicate that diet may not play a large role in the etiology of RCC in male smokers, although further examination of these associations in nonsmokers, women and diverse racial populations is warranted.

Reducing paediatric overweight and obesity through motivational interviewing: study protocol for a randomised controlled trial in the AAP PROS research network.

INTRODUCTION: Primary care remains an underused venue for prevention and management of paediatric overweight and obesity. A prior trial demonstrated a significant impact of paediatrician/nurse practitioner (Ped/NP)-and registered dietitian (RD)-delivered motivational interviewing (MI) on child body mass index (BMI). The study described here will test the effectiveness of an enhanced version of this primary care-based MI counselling intervention on child BMI. METHODS AND ANALYSIS: This cluster randomised effectiveness trial includes 24 Ped/NPs from 18 paediatric primary care practices that belong to the American Academy of Pediatrics (AAP) national Pediatric Research in Office Settings (PROS) practice-based research network. To date, practices have been randomised (nine to intervention and nine to usual care). Intervention Ped/NPs have been trained in MI, behavioural therapy, billing/coding for weight management and study procedures. Usual care Ped/NPs received training in billing/coding and study procedures only. Children 3- 11 years old with BMI >the 85th percentile were identified via electronic health records (EHRs). Parents from intervention practices have been recruited and enrolled. Over about 2 years, these parents are offered approximately 10 MI-based counselling sessions (about four in person sessions with their child's Ped/NP and up to six telephonic sessions with a trained RD). The primary outcome is change in child BMI (defined as per cent from median BMI for age and sex) over the study period. The primary comparison is between eligible children in intervention practices whose parents enrol in the study and all eligible children in usual care practices. Data sources will include EHRs, billing records, surveys and counselling call notes. ETHICS AND DISSEMINATION: Institutional Review Board approval was obtained from the AAP. All Ped/NPs provided written informed consent, and intervention group parents provided consent and Health Insurance Portability and Accountability Act (HIPAA) authorisation. Findings will be disseminated through peer-reviewed publications, conference presentations and appropriate AAP channels. TRIAL REGISTRATION NUMBER: NCT03177148; Pre-results.

Vitamin E intake and risk of esophageal and gastric cancers in the NIH-AARP Diet and Health Study.

We investigated the association of dietary alpha-tocopherol, gamma-tocopherol and supplemental vitamin E intake with the risk of esophageal squamous cell carcinoma (n = 158), esophageal adenocarcinoma (n = 382), gastric cardia adenocarcinoma (n = 320) and gastric noncardia adenocarcinoma (GNCA; n = 327) in the NIH-AARP Diet and Health Study, a cohort of approximately 500,000 people. Data on dietary and supplemental vitamin E intake were collected using a validated questionnaire at baseline and were analyzed using Cox regression models. Intakes were analyzed as continuous variables and as quartiles. For dietary alpha-tocopherol, we found some evidence of association with decreased esophageal squamous cell carcinoma and increased esophageal adenocarcinoma risk in the continuous analyses, with adjusted hazard ratios and 95% confidence intervals of 0.90 (0.81-0.99) and 1.05 (1.00-1.11), respectively, per 1.17 mg (half the interquartile range) increased intake. However, in quartile analyses, the p value for trend was nonsignificant for both these cancers. There was no association between dietary alpha-tocopherol and gastric cardia adenocarcinoma or GNCA. We observed no statistically significant associations with gamma-tocopherol. For supplemental vitamin E, the results were mainly null, except for a significantly lower risk of GNCA with higher doses of supplemental vitamin E. An increase of 71 mg/day (half the interquartile range) in supplemental vitamin E had an hazard ratio (95% confidence interval) of 0.92 (0.85-1.00) and the p value for trend in the quartile analysis was 0.015.

HPV vaccine recommendation profiles among a national network of pediatric practitioners: understanding contributors to parental vaccine hesitancy and acceptance.

Background: Practitioner communication is one of the most important influences and predictors of HPV vaccination uptake. The objective of this study was to conduct a latent class analysis characterizing pediatric practitioner HPV recommendation patterns. Methods: Pediatric practitioners of the American Academy of Pediatrics' (AAP) Pediatric Research in Office Settings (PROS) national network completed an online survey where they were presented with 5 hypothetical vignettes of well child visits and responded to questions. Questions asked about their use of communication strategies, assessments about the adolescent patient becoming sexually active in the next 2 years for decision-making about HPV vaccine recommendation, and peer norms. Latent class analysis characterized practitioner subgroups based on their response patterns to 10 survey questions. Multinomial logistic regression examined practitioner characteristics associated with each profile. Results: Among 470 respondents, we identified three distinct practitioner HPV vaccine recommendation profiles: (1) Engagers (52%) followed national age-based guidelines, strongly recommended HPV vaccination, and perceived peers as strongly recommending; (2) Protocol Followers (20%) also strongly recommended HPV vaccination, but were less likely to engage families in a discussion about benefits; and (3) Ambivalent HPV Vaccine Recommenders (28%) delayed or did not recommend HPV vaccination and were more likely to use judgment about whether adolescents will become sexually active in the next two years. Practicing in a suburban setting was associated with twice the odds of being an Ambivalent Recommender relative to being an Engager (OR = 2.2; 95% CI:1.1-4.1). Conclusions: Findings underscore the importance of continued efforts to bolster practitioner adoption of evidence-based approaches to HPV vaccine recommendation especially among Ambivalent Recommenders.

Intakes of fruit, vegetables, and specific botanical groups in relation to lung cancer risk in the NIH-AARP Diet and Health Study.

Increased fruit and vegetable consumption may protect against lung cancer, although epidemiologic findings are inconclusive. The authors prospectively examined associations between lung cancer risk and intakes of fruit, vegetables, and botanical subgroups in 472,081 participants aged 50-71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline (1995-1996) with a 124-item dietary questionnaire. A total of 6,035 incident lung cancer cases were identified between 1995 and 2003. Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women. Higher consumption of several botanical subgroups, however, was significantly inversely associated with risk, but only in men. For example, the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae, convolvulaceae, and umbelliferae were 0.82 (95% confidence interval (CI): 0.73, 0.91), 0.86 (95% CI: 0.75, 0.96), and 0.86 (95% CI: 0.78, 0.96), respectively; corresponding relative risks in women were 0.97 (95% CI: 0.85, 1.12), 0.95 (95% CI: 0.83, 1.09), and 0.92 (95% CI: 0.80, 1.06). These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men, although the findings could also be due to residual confounding by smoking or chance.

Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study.

Supplemental vitamin E (alpha-tocopherol) has been linked to lower prostate cancer incidence in one randomized trial and several, although not all, observational studies. The evidence regarding dietary intake of individual vitamin E isoforms and prostate cancer is limited and inconclusive, however. We prospectively examined the relations of supplemental vitamin E and dietary intakes of alpha-, beta-, gamma-, and delta- tocopherols to prostate cancer risk among 295,344 men, ages 50 to 71 years and cancer-free at enrollment in 1995 to 1996, in the NIH-AARP Diet and Health Study. At baseline, participants completed a questionnaire that captured information on diet, supplement use, and other factors. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) of prostate cancer. During 5 years of follow-up, 10,241 incident prostate cancers were identified. Supplemental vitamin E intake was not related to prostate cancer risk (for >0-99, 100-199, 200-399, 400-799, and > or = 800 IU/d versus never use: RR, 0.97, 0.89, 1.03, 0.99, and 0.97 (95% CI, 0.87-1.07) respectively; Ptrend = 0.90). However, dietary gamma-tocopherol, the most commonly consumed form of vitamin E in the United States, was significantly inversely related to the risk of advanced prostate cancer (for highest versus lowest quintile: RR, 0.68; 95% CI, 0.56-0.84; Ptrend = 0.001). These results suggest that supplemental vitamin E does not protect against prostate cancer, but that increased consumption of gamma-tocopherol from foods is associated with a reduced risk of clinically relevant disease. The potential benefit of gamma-tocopherol for prostate cancer prevention deserves further attention.

Serum and dietary vitamin E in relation to prostate cancer risk.

Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. We investigated whether serum alpha-tocopherol or intake of vitamin E (eight tocopherols and tocotrienols) was associated with prostate cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency questionnaire and food chemistry analyses. Proportional hazard models were used to determine multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). Higher serum alpha-tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest quintile; Ptrend = 0.03) and was strongly and inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; Ptrend = 0.002). The inverse serum alpha-tocopherol-prostate cancer association was greater among those who were supplemented with either alpha-tocopherol or beta-carotene during the trial. There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols. In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer.

Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

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.

A prospective investigation of height and prostate cancer risk.

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 [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); P(trend) = 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); P(trend) = 0.0008, P(interaction) = 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.