Recognition of the complex, multidimensional relationship between excess adiposity and cancer control outcomes has motivated the scientific community to seek new research models and paradigms. The ...National Cancer Institute developed an innovative concept to establish a center grant mechanism in nutrition, energetics, and physical activity, referred to as the Transdisciplinary Research on Energetics and Cancer (TREC) Initiative. This paper gives an overview of the 2011âeuro"2016 TREC Collaborative Network and the 15 research projects being conducted at the centers. Four academic institutions were awarded TREC center grants in 2011: Harvard University, University of California San Diego, University of Pennsylvania, and Washington University in St. Louis. The Fred Hutchinson Cancer Research Center is the Coordination Center. The TREC research portfolio includes three animal studies, three cohort studies, four randomized clinical trials, one cross-sectional study, and two modeling studies. Disciplines represented by TREC investigators include basic science, endocrinology, epidemiology, biostatistics, behavior, medicine, nutrition, physical activity, genetics, engineering, health economics, and computer science. Approximately 41,000 participants will be involved in these studies, including children, healthy adults, and breast and prostate cancer survivors. Outcomes include biomarkers of cancer risk, changes in weight and physical activity, persistent adverse treatment effects (e.g., lymphedema, urinary and sexual function), and breast and prostate cancer mortality. The NIH Science of Team Science group will evaluate the value added by this collaborative science. However, the most important outcome will be whether this transdisciplinary initiative improves the health of Americans at risk of cancer as well as cancer survivors.PUBLICATION ABSTRACT
BACKGROUND Heavy alcohol drinking is associated with a dose-dependent increase in blood pressure, but data on the relation between alcohol consumption and mortality in hypertensive patients are ...sparse. OBJECTIVE To assess the relation between light to moderate alcohol consumption and total mortality from cardiovascular disease (CVD) among men with hypertension. PARTICIPANTS AND DESIGN From the Physicians' Health Study enrollment cohort of 88 882 men who provided self-reported information on alcohol intake, we identified a group of 14 125 men with a history of current or past treatment for hypertension who were free of myocardial infarction, stroke, cancer, or liver disease at baseline. MAIN OUTCOME MEASURE Comparison of total and CVD mortality among men with hypertension who had reported to be either nondrinkers or rare drinkers, or light to moderate drinkers. RESULTS During 75 710 person-years of follow-up, there were 1018 deaths, including 579 from CVD. Compared with individuals who rarely or never drank alcoholic beverages, those who reported monthly, weekly, and daily alcohol consumption, respectively, had multivariate adjusted relative risks (RRs) for CVD mortality of 0.83 (95% confidence interval CI, 0.62-1.13), 0.61 (CI, 0.49-0.77), and 0.56 (CI, 0.44-0.71) (P<.001 for linear trend). In the same groups, RRs for total mortality were respectively 0.86 (CI, 0.67-1.10), 0.72 (CI, 0.60-0.86), and 0.73 (CI, 0.61-0.87) (P<.001 for linear trend). Among men with a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher, the RRs for CVD mortality were, respectively, 1.00 (referent), 0.82 (CI, 0.56-1.21), 0.64 (CI, 0.48-0.85), and 0.56 (CI, 0.42-0.75) (P<.001 for linear trend). On the other hand, we found no significant association between moderate alcohol consumption and cancer mortality (P = .8 for linear trend). CONCLUSION These results, which require confirmation in other large-scale studies, suggest that light to moderate alcohol consumption is associated with a reduction in risk of total and CVD mortality in hypertensive men.Arch Intern Med. 2004;164:623-628-->
IntroductionMobility limitation is a component of frailty that shares a bidirectional relationship with cardiovascular disease (CVD). Whether established CVD prevention therapies such as aspirin can ...prevent frailty and mobility limitation is unknown.MethodsProspective cohort of 14,896 participants >60 years in the Physicians’ Health Study I, a completed randomized controlled trial of aspirin (1982-1986) with extended post-trial follow-up. Annual questionnaires (1986-2001) collected data on aspirin use, lifestyle and other clinical factors. Aspirin exposure was computed from 1986-2001 when walking pace was assessed. Average aspirin use was categorized for each participant<60 d/yr, 60-180 d/yr, or >180 d/yr over 15 years. Self-assessed walking pace was categorized asdon’t walk regularly, easy casual <2mph, normal ≥2-2.9mph, or brisk or very brisk ≥3mph. Propensity scoring created covariate balance across the categories of aspirin use. Aspirin randomization group was included as a covariate in the propensity score. Multinomial logistic regression models estimated the odds of prevalent mobility limitation according to level of aspirin use.ResultsMedian age was 70 years (range 60-101); mean duration of aspirin use was 9 years (range 0-15). 15.3%, 62.1%, and 22.6% of participants reported aspirin use <60, 60-180, and ≥180 days/year, respectively. Those with greater aspirin use were more likely to drink alcohol daily, have smoked previously, and have hypertension, prevalent CVD and stroke. Lower frequency of aspirin was associated with Coumadin use and bleeding history. For walking, 12% reported not walking regularly, 12.6% walked <2 mph, 44.9% walked ≥2-2.9 mph, and 30.9% walked ≥3 mph. After propensity score adjustment, the estimated odds ratios (95% confidence intervals) of not walking regularly were 0.78 (0.69-0.90) and 0.84 (0.72-0.99) for 60-180 and >180 days/yr of aspirin use, respectively, in comparison to <60 days. In analyses considering all walking speed categories, increasing aspirin use was consistently associated with greater walking speed (p-trend=0.017).ConclusionsThese results suggest that long-term aspirin use prevents mobility limitation, defined by walking speed, possibly due to anti-inflammatory effects.
Abstract
Background: Selenoprotein P (SelP) is the most common selenoprotein in serum and delivers selenium around the body, carrying up to ten selenocysteine residues per polypeptide. Antioxidants ...such as selenium may decrease the risk of developing prostate cancer (PCa). One study observed that serum SelP levels were lower in PCa cases than in controls while another found the expression of the gene, SEPP1, decreased with progression from normal prostate tissue to carcinoma to metastatic disease. Genetic variation in SEPP1 may also influence PCa risk or progression, or may modify the effects of selenium. We examined the association of single nucleotide polymorphisms (SNPs) in SEPP1 with PCa risk and survival, and tested for interactions with plasma selenium levels.
Methods: The Physicians' Health Study (PHS) is a prospective cohort of 22,071 US physicians, of whom 2,584 were diagnosed with PCa between 1982 and 2005. Blood was collected from 68% of participants at baseline. We used a nested case-control study of 1,352 PCa cases and 1,382 controls matched on age, smoking status, and follow-up time; analyses were restricted to Caucasians. Using the HapMap database, we selected 5 SNPs to capture variation with a minor allele frequency >5% within SEPP1 and 5 kb up- and downstream. Four SNPs had high genotyping success (92–97%); the other failed genotyping, however, it tagged only itself so did not reduce the coverage. The incidence analysis used unconditional logistic regression, adjusting for matching factors. For survival analysis, individuals were censored at death or the end of follow-up; PCa deaths or metastases were considered lethal events (n=191). Plasma selenium levels were measured on 805 cases and 549 controls.
Results: Two of the four SNPs were significantly associated with risk of incident PCa. For rs11959466, each additional T allele significantly increased the risk of PCa (odds ratio (OR)=1.31; 95% confidence interval (CI): 1.02, 1.69; ptrend=0.03), while for rs13168440, the minor allele homozygote genotype (CC) was associated with a decreased risk compared to the homozygote TT referent (OR=0.56, 95% CI: 0.33, 0.96). Moreover, there was a significant interaction of rs13168440 with quartiles of plasma selenium; increasing levels were associated with a decreased risk of PCa only among men with the minor allele (OR=0.76; 95% CI: 0.62, 0.93; pinteraction=0.02). None of the four SNPs was associated with PCa survival among the cases.
Conclusions: Genetic variation within SEPP1 was associated with PCa incidence and may modify the association of selenium. Considering the multiple hypotheses tested, replication of these findings in an independent data set is needed to confirm or refute these results.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A122.
Although subjects randomized into clinical trials tend to have different mortality experiences from those not randomized, few studies have examined how baseline characteristics may explain these ...differences. We used the recruitment experience of the Physicians' Health Study (PHS) to describe and compare subgroups of subjects ultimately randomized — or not — into the PHS. A total of 112,528 male physicians ages 40–84 years responded to letters of invitation and baseline questionnaires sent to 261,248 subjects. Baseline information was collected on eligibility criteria, plus lifestyle and clinical risk factors. Total, cardiovascular, cancer, and other mortality were determined through the National Death Index after a mean follow-up of 5.39 years. Respondents had 19 and 19% lower total and cardiovascular mortality rates than nonrespondents. Similarly, willing respondents were 19 and 16% less likely to die than unwilling respondents. However, much of this difference in mortality was explained by disease and lifestyle factors. Respondents who were eligible for the PHS had significantly lower age-adjusted relative risks (RRs) that were attenuated but remained substantially below 1 upon multivariate adjustment in models for total (RRs from 0.48 to 0.79), cardiovascular (from 0.40 to 0.85), and cancer mortality (from 0.55 to 0.87). Finally, a nearly halving in the age-adjusted risk of total and cause-specific mortality among men completing a run-in and randomized into PHS compared with those not randomized was nominally altered upon adding all covariates into multivariate models. In conclusion, a difference in mortality rates according to willingness to participate in a trial was explained by disease and lifestyle factors. In contrast, diseases and risk factors explain some, but not all, of the lower mortality rates of physicians based on eligibility status and their ability to complete a run-in phase.
Abstract
PR-1
Background
Basic science and observational studies support a potential role of antioxidants, including vitamins E and C, in the prevention of cancer. Previous trials have suggested a ...possible benefit of vitamin E, in particular on prostate cancer. Few long-term trials have evaluated vitamin C alone in the prevention of cancer. Despite uncertainty regarding long-term effects, use of vitamin supplementation remains highly prevalent in the US.
Methods
The Physicians’ Health Study II (PHS II) evaluated the roles of supplementation with vitamin E (400 IU every other day) and vitamin C (500 mg daily) on risk of cancer in a randomized, double-blind, placebo-controlled trial of 14,641 U.S. male physicians initially aged ≥50 years. The trial included 1,274 (8.7%) men with prevalent cancer at randomization. The randomized vitamin E and C trial components terminated as scheduled on August 31, 2007, and identification of cancer endpoints that occurred prior to that date will continue through September 30, 2008. The primary endpoint of the vitamin E component was prostate cancer, with total cancer (defined as excluding non-melanoma skin cancer) as a secondary endpoint. For vitamin C, the primary endpoint was total cancer. All endpoints were reviewed and confirmed by an Endpoints Committee of physicians blinded to randomized treatment assignment. High rates of morbidity and mortality follow-up have been maintained in the PHS II.
Results
During a median (interquartile range) follow-up of 7.6 (7.1 to 9.6) years among men with a mean baseline age of 64.3 years, there have been 1,929 cases of cancer, including 1,013 cases of prostate cancer. Based upon preliminary results, those randomized to vitamin E had a relative risk of prostate cancer of 0.95 (490 events in the active group vs. 523 in the placebo group; 95% CI, 0.84-1.07; p=0.39), and a relative risk of total cancer of 1.04 (978 vs 951; 95% confidence interval, 0.95-1.14; p=0.38). For those randomized to vitamin C, the relative risk of total cancer was 1.00 (964 events in the active group, 965 in placebo; 95% CI, 0.92-1.10; p=0.95).
In addition to updating the results above, we will also present the results for other site-specific cancers, as well as analyses that consider the effects of compliance, effect modification by baseline risk factors and baseline cancer, and potential adverse effects.
Conclusion
These preliminary data from a large-scale prevention trial of long duration indicate no beneficial effect of vitamin E supplementation on either prostate or total cancer, nor a beneficial effect of vitamin C supplementation on total cancer. These data will help inform clinical and public health recommendations regarding effects of vitamin E or vitamin C supplementation on risks of total and site-specific cancers.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-1.
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