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.

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.

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.

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.

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.

Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers.

Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating ß-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive ß-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant ß-carotene among men not taking ß-carotene supplements should be interpreted cautiously, as they are likely due to chance.

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 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.

Associations between functional polymorphisms in antioxidant defense genes and urinary oxidative stress biomarkers in healthy, premenopausal women.

Functional polymorphisms in endogenous antioxidant defense genes including manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX-1) have been linked with risk of cancer at multiple sites. Although it is presumed that these germline variants impact disease risk by altering the host's ability to detoxify mutagenic reactive oxygen species, very few studies have directly examined this hypothesis. Concentrations of 8-isoprostane F2α (8-iso-PGF2α) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoxdG)-sensitive indicators of lipid peroxidation and DNA oxidation, respectively-were measured in 24-h urine samples obtained from 93 healthy, premenopausal women participating in a dietary intervention trial. In addition, DNA was extracted from blood for genotyping of MnSOD Val16Ala, CAT-262 C > T, and GPX1 Pro198Leu genotypes by Taqman assay. Although geometric mean concentrations of 8-iso-PGF2(α) and 8-oxoxdG varied across several study characteristics including race, education level, body mass index, and serum antioxidant levels, there was little evidence that these biomarkers differed across any of the examined genotypes. In summary, functional polymorphisms in endogenous antioxidant defense genes do not appear to be strongly associated with systemic oxidative stress levels in young, healthy women.

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 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.

Dietary supplements and human health: for better or for worse?

Encouraged by the potential health benefits of higher dietary intake of substances with beneficial properties, the use of supplements containing these compounds has increased steadily over recent years. The effects of several of these, many of which are antioxidants, have been supported by data obtained in vitro, in animal models, and often by human studies as well. However, as carefully controlled human supplementation trials have been conducted, questions about the efficacy and safety of these supplements have emerged. In this Educational Paper, three different supplements were selected for consideration of the benefits and risks currently associated with their intake. The selected supplements include ß-carotene, selenium, and genistein. The use of each is discussed in the context of preclinical and clinical data that provide evidence for both their use in reducing disease incidence and the possible liabilities that accompany their enhanced consumption. Variables that may influence their impact, such as lifestyle habits, baseline nutritional levels, and genetic makeup are considered and the application of these issues to broader classes of supplements is discussed.

Effects of beta-carotene supplementation on molecular markers of lung carcinogenesis in male smokers.

Two primary prevention trials unexpectedly showed adverse effects of supplemental beta-carotene on lung cancer incidence in cigarette smokers. To elucidate the molecular mechanisms that might underlie these effects, we studied the immunohistochemical expression of cytochrome P450 1A1, 1A2, and 2E1, retinoic acid receptor beta, activated protein-1 elements, cyclin D1, and Ki67 in lung tumors and, when available, adjacent normal tissues obtained from incident cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Archival lung tissue was available from 52 men randomized to receive 20 mg of beta-carotene per day and 30 men randomized to the placebo arm, all of whom were diagnosed with incident non-small-cell lung carcinoma during the course of the trial and subsequently underwent radical pulmonary resection. In normal-appearing bronchial epithelium, positive staining for cyclin D1 was observed in 23% of cases in the beta-carotene group and 0% of cases in the placebo group (based on only 3 of 13 versus 0 of 11 cases staining positively, however; P = 0.04), with no differences in expression noted in lung tumor tissue (P = 0.48). There were no statistically significant differences in Ki67 expression in normal or cancerous lung tissue between intervention groups, although a small increase in staining in tumors was noted among cases in the beta-carotene versus placebo group (88% versus 71% of cases stained positive, respectively; P = 0.13). Contrary to expectation, beta-carotene supplementation had no apparent effect on retinoic acid receptor-beta expression. These findings suggest that male smokers supplemented with beta-carotene may have had an increased risk of lung cancer due to aberrant cell growth, although our results are based on a relatively small number of cases and require confirmation in other completed trials of beta-carotene supplementation.

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.

Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer.

BACKGROUND: The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear. METHODS: We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. RESULTS: Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile. CONCLUSION: Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

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.

Genetic variation in sodium-dependent ascorbic acid transporters and risk of gastric cancer in Poland.

Higher ascorbic acid consumption is associated with a reduced risk of gastric cancer in numerous epidemiologic studies. We investigated whether single nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2--genes that encode key ascorbic acid transport proteins--affect gastric cancer risk in 279 incident cases and 414 age- and gender-matched controls drawn from a population-based case-control study in Poland. Compared to subjects who were homozygous for the common G allele of the SLC23A2 SNP rs12479919, carriers of the AA genotype had a 41% lower risk of gastric cancer [odds ratio (OR)=0.59, 95% confidence interval (CI): 0.36-0.95; P trend=0.06]. A haplotype that contained the common allele of the rs6139591, rs2681116 and rs14147458 SNPs in SLC23A2 was also significantly inversely associated with gastric malignancy. No other polymorphisms in either gene were related to risk, and there was no effect modification by ascorbic acid intake. These findings suggest that genetic variation in SLC23A2 impacts gastric cancer risk, although confirmation in other studies is required.