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1.  Diet and prostate cancer prevention 
World journal of urology  2012;30(2):157-165.
To evaluate the present human-based evidence that diet is related to the risk and outcome of prostate cancer.
Review of major case–control and cohort studies, and experimental trials evaluating the effect of diet or dietary constituents on the risk of prostate cancer.
Although non-experimental studies have suggested several dimensions of diet and several dietary components as related to risk and outcome of prostate cancer, the results of these studies are inconsistent. There is limited evidence that a diet that emphasizes plant products is associated with diminished risk of prostate cancer and of aggressive prostate cancer.
The non-experimental epidemiologic evidence that has now accrued justifies trials of dietary intervention for those at elevated risk of prostate cancer.
PMCID: PMC4303588  PMID: 22249340
Diet; Nutrition; Epidemiology; Chemoprevention; Prevention
2.  Addressing Tobacco Use in Patients With Cancer: A Survey of American Society of Clinical Oncology Members 
Journal of Oncology Practice  2013;9(5):258-262.
Among ASCO members who responded to an online survey about their practice patterns regarding tobacco, most believe that tobacco cessation is important and frequently assess tobacco at initial visit, but few provide cessation support.
Assessing tobacco use and providing cessation support is recommended by the American Society for Clinical Oncology (ASCO). The purpose of this study was to evaluate practice patterns and perceptions of tobacco use and barriers to providing cessation support for patients with cancer.
In 2012, an online survey was sent to 18,502 full ASCO members asking about their practice patterns regarding tobacco assessment, cessation support, perceptions of tobacco use, and barriers to providing cessation support for patients with cancer. Responses from 1,197 ASCO members are reported.
At initial visit, most respondents routinely ask patients about tobacco use (90%), ask patients to quit (80%), and advise patients to stop using tobacco (84%). However, only 44% routinely discuss medication options with patients, and only 39% provide cessation support. Tobacco assessments decrease at follow-up assessments. Most respondents (87%) agree or strongly agree that smoking affects cancer outcomes, and 86% believe cessation should be a standard part of clinical cancer care. However, only 29% report adequate training in tobacco cessation interventions. Inability to get patients to quit (72%) and patient resistance to treatment (74%) are dominant barriers to cessation intervention, but only 8% describe cessation as a waste of time.
Among ASCO members who responded to an online survey about their practice patterns regarding tobacco, most believe that tobacco cessation is important and frequently assess tobacco at initial visit, but few provide cessation support. Interventions are needed to increase access to tobacco cessation support for patients with cancer.
PMCID: PMC3770508  PMID: 23943904
3.  Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials 
Journal of Clinical Oncology  2012;30(23):2869-2875.
Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials.
Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument.
Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group.
Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.
PMCID: PMC3410402  PMID: 22689794
4.  Practice Patterns and Perceptions of Thoracic Oncology Providers on Tobacco Use and Cessation in Cancer Patients 
Tobacco use is associated with poor outcomes in cancer patients, but there is little information on the practice patterns or perceptions of tobacco use and smoking cessation by oncology providers.
An online survey of practices, perceptions, and barriers to tobacco assessment and cessation in cancer patients was conducted in members of the International Association for the Study of Lung Cancer (IASLC). Responses of physician level respondents were analyzed and reported.
Responses from 1,507 IASLC members who completed the survey are reported representing 40.5% of IASLC members. Over 90% of physician respondents believe current smoking affects outcome and that cessation should be a standard part of clinical care. At the initial patient visit, 90% ask patients about tobacco use, 79% ask patients if they will quit, 81% advise patients to stop tobacco use, but only 40% discuss medication options, 39% actively provide cessation assistance, and fewer yet address tobacco at follow-up. Dominant barriers to physician cessation effort are pessimism regarding their ability to help patients stop using tobacco (58%) and concerns about patient resistance to treatment (67%). Only 33% report themselves adequately trained to provide cessation interventions.
Physicians who care for lung cancer patients recognize the importance of tobacco cessation as a necessary part of clinical care, but many still do not routinely provide assistance to their patients. Increasing tobacco cessation will require increased assessment and cessation at diagnosis and during follow-up, increased clinician education, and improved tobacco cessation methods.
PMCID: PMC3628367  PMID: 23529191
smoking; tobacco; survey; thoracic; oncologists; cancer; cessation
5.  Phase III Trial of Selenium to Prevent Prostate Cancer in Men with High-Grade Prostatic Intraepithelial Neoplasia: SWOG S9917 
The threat of prostate cancer (PC) and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of PC, and substantial evidence suggests that men with HGPIN are in need of PC prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against PC motivated the study we report here: A double-blind, randomized, placebo-controlled trial of selenium 200 (mcg/day) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to PC over a three-year period. This NCI Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212, selenium; 211, placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium, and 75.5%, placebo) had a Gleason score of ≤ 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced PC risk (relative risk = 0.82; 95% confidence interval, 0.40–1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (< 106 ng/ml). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on PC risk. The 36% PC rate in men with HGPIN indicates the association of this lesion with an elevated PC risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics.
PMCID: PMC3208719  PMID: 21896650
Chemoprevention; selenium; prostate cancer; intraepithelial neoplasia; prevention; clinical trials
6.  Methyl Selenocysteine: single-dose pharmacokinetics in men 
The recently published report of the SELECT evaluation of selenium and vitamin E provided strong evidence that selenium 200mcg/day in the form of selenomethionine does not protect selenium-replete men against prostate or any other cancer. This appears to refute the result of the much smaller Nutritional Prevention of Cancer (NPC) trial of selenium. Since SELECT did not test the NPC agent, is possible that the difference between the two trials stems partly from the use of different agents: selenomethionine in SELECT, selenized yeast in the NPC trial. One of the organic selenium forms suspected of having strong chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine. This study characterizes the single-dose pharmacokinetics of methyl selenocysteine.
PMCID: PMC3208773  PMID: 21846796
selenium; selenomethionine; methyl selenocysteine; chemoprevention; pharmacokinetics
7.  Organ-Specific Exposure and Response to Sulforaphane, a Key Chemopreventive Ingredient in Broccoli: Implications for Cancer Prevention 
The British journal of nutrition  2012;109(1):10.1017/S0007114512000657.
Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 days. Tissue distribution of SF was measured by a high-performance liquid chromatography-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective Phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastrointestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2–4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3 to 6 fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritizing organs for further chemopreventive study of SF.
PMCID: PMC3393776  PMID: 22464629
Chemoprevention; nutrition; Phase 2 enzyme; sulforaphane
8.  When natural selection should optimize speed-accuracy trade-offs 
PMCID: PMC3989582  PMID: 24782703
decision-making; value; reward; error; Bayes risk; drift-diffusion; mechanism; evolution
9.  Adaptive Sampling of Information in Perceptual Decision-Making 
PLoS ONE  2013;8(11):e78993.
In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy.
PMCID: PMC3842256  PMID: 24312172
10.  Inclusive fitness theory and eusociality 
Abbot, Patrick | Abe, Jun | Alcock, John | Alizon, Samuel | Alpedrinha, Joao A. C. | Andersson, Malte | Andre, Jean-Baptiste | van Baalen, Minus | Balloux, Francois | Balshine, Sigal | Barton, Nick | Beukeboom, Leo W. | Biernaskie, Jay M. | Bilde, Trine | Borgia, Gerald | Breed, Michael | Brown, Sam | Bshary, Redouan | Buckling, Angus | Burley, Nancy T. | Burton-Chellew, Max N. | Cant, Michael A. | Chapuisat, Michel | Charnov, Eric L. | Clutton-Brock, Tim | Cockburn, Andrew | Cole, Blaine J. | Colegrave, Nick | Cosmides, Leda | Couzin, Iain D. | Coyne, Jerry A. | Creel, Scott | Crespi, Bernard | Curry, Robert L. | Dall, Sasha R. X. | Day, Troy | Dickinson, Janis L. | Dugatkin, Lee Alan | El Mouden, Claire | Emlen, Stephen T. | Evans, Jay | Ferriere, Regis | Field, Jeremy | Foitzik, Susanne | Foster, Kevin | Foster, William A. | Fox, Charles W. | Gadau, Juergen | Gandon, Sylvain | Gardner, Andy | Gardner, Michael G. | Getty, Thomas | Goodisman, Michael A. D. | Grafen, Alan | Grosberg, Rick | Grozinger, Christina M. | Gouyon, Pierre-Henri | Gwynne, Darryl | Harvey, Paul H. | Hatchwell, Ben J. | Heinze, Jürgen | Helantera, Heikki | Helms, Ken R. | Hill, Kim | Jiricny, Natalie | Johnstone, Rufus A. | Kacelnik, Alex | Kiers, E. Toby | Kokko, Hanna | Komdeur, Jan | Korb, Judith | Kronauer, Daniel | Kümmerli, Rolf | Lehmann, Laurent | Linksvayer, Timothy A. | Lion, Sébastien | Lyon, Bruce | Marshall, James A. R. | McElreath, Richard | Michalakis, Yannis | Michod, Richard E. | Mock, Douglas | Monnin, Thibaud | Montgomerie, Robert | Moore, Allen J. | Mueller, Ulrich G. | Noë, Ronald | Okasha, Samir | Pamilo, Pekka | Parker, Geoff A. | Pedersen, Jes S. | Pen, Ido | Pfennig, David | Queller, David C. | Rankin, Daniel J. | Reece, Sarah E. | Reeve, Hudson K. | Reuter, Max | Roberts, Gilbert | Robson, Simon K. A. | Roze, Denis | Rousset, Francois | Rueppell, Olav | Sachs, Joel L. | Santorelli, Lorenzo | Schmid-Hempel, Paul | Schwarz, Michael P. | Scott-Phillips, Tom | Shellmann-Sherman, Janet | Sherman, Paul W. | Shuker, David M. | Smith, Jeff | Spagna, Joseph C. | Strassmann, Beverly | Suarez, Andrew V. | Sundström, Liselotte | Taborsky, Michael | Taylor, Peter | Thompson, Graham | Tooby, John | Tsutsui, Neil D. | Tsuji, Kazuki | Turillazzi, Stefano | Úbeda, Francisco | Vargo, Edward L. | Voelkl, Bernard | Wenseleers, Tom | West, Stuart A. | West-Eberhard, Mary Jane | Westneat, David F. | Wiernasz, Diane C. | Wild, Geoff | Wrangham, Richard | Young, Andrew J. | Zeh, David W. | Zeh, Jeanne A. | Zink, Andrew
Nature  2011;471(7339):10.1038/nature09831.
PMCID: PMC3836173  PMID: 21430721
11.  A Mechanism for Value-Sensitive Decision-Making 
PLoS ONE  2013;8(9):e73216.
We present a dynamical systems analysis of a decision-making mechanism inspired by collective choice in house-hunting honeybee swarms, revealing the crucial role of cross-inhibitory ‘stop-signalling’ in improving the decision-making capabilities. We show that strength of cross-inhibition is a decision-parameter influencing how decisions depend both on the difference in value and on the mean value of the alternatives; this is in contrast to many previous mechanistic models of decision-making, which are typically sensitive to decision accuracy rather than the value of the option chosen. The strength of cross-inhibition determines when deadlock over similarly valued alternatives is maintained or broken, as a function of the mean value; thus, changes in cross-inhibition strength allow adaptive time-dependent decision-making strategies. Cross-inhibition also tunes the minimum difference between alternatives required for reliable discrimination, in a manner similar to Weber's law of just-noticeable difference. Finally, cross-inhibition tunes the speed-accuracy trade-off realised when differences in the values of the alternatives are sufficiently large to matter. We propose that the model, and the significant role of the values of the alternatives, may describe other decision-making systems, including intracellular regulatory circuits, and simple neural circuits, and may provide guidance in the design of decision-making algorithms for artificial systems, particularly those functioning without centralised control.
PMCID: PMC3759446  PMID: 24023835
12.  Altered folate availability modifies the molecular environment of the human colon: implications for colorectal carcinogenesis 
Low folate status increases colorectal cancer risk whereas abundant supplementation may paradoxically increase risk. The mechanisms are unknown.
To define molecular pathways in the human colon altered by either dietary folate depletion (followed by repletion), or by supplementation.
10 healthy volunteers consumed a low folate diet for 12 weeks. During the last 4 weeks, folic acid (1 mg/day) was administered. In a second study, 10 other subjects were provided supplemental folic acid for 8 weeks. Rectosigmoid biopsies were obtained at measured intervals in both studies for assessment of primary endpoints: genome-wide gene expression, genomic DNA methylation, promoter methylation (depletion study only) and p53 DNA strand breaks.
Serum and rectosigmoid folate concentrations accurately tracked all changes in folate delivery (p<0.05). Gene array analysis revealed that folate depletion downregulated genes involved in immunity, inflammation, cell cycle and mitochondrial energy pathways; repletion produced reversal in most instances. Similarly, supplementation upregulated multiple inflammatory- and immune-related pathways, and in addition altered several 1-carbon related enzymes (p<0.001). Neither genomic or promoter-specific DNA methylation changed over the course of the depletion/repletion protocol; nor did genomic methylation change due to supplementation. p53 strand breaks increased with depletion after 12 weeks.
Depletion downregulates, whereas repletion or supplementation upregulates, pathways related to inflammation and immune response. Supplementation also altered expression of several pivotal genes involved in 1-carbon metabolism. These changes occurred in the absence of changes in gene methylation. Modest changes in folate delivery create substantial changes in the molecular milieu of the human colon.
PMCID: PMC3742550  PMID: 21321062
Folic acid; folate depletion; folate supplementation; colonic carcinogenesis; one carbon metabolism; inflammation; gene expression profiling; DNA methylation
13.  Dietary Supplements and Cancer Prevention: Balancing Potential Benefits Against Proven Harms 
Nutritional supplementation is now a multibillion-dollar industry, and about half of all US adults take supplements. Supplement use is fueled in part by the belief that nutritional supplements can ward off chronic disease, including cancer, although several expert committees and organizations have concluded that there is little to no scientific evidence that supplements reduce cancer risk. To the contrary, there is now evidence that high doses of some supplements increase cancer risk. Despite this evidence, marketing claims by the supplement industry continue to imply anticancer benefits. Insufficient government regulation of the marketing of dietary supplement products may continue to result in unsound advice to consumers. Both the scientific community and government regulators need to provide clear guidance to the public about the use of dietary supplements to lower cancer risk.
PMCID: PMC3352833  PMID: 22534785
14.  Autofluorescence-Guided Surveillance for Oral Cancer 
Early detection of oral premalignant lesions (OPL) and oral cancers (OC) is critical for improved survival. We evaluated if the addition of autofluorescence visualization (AFV) to conventional white-light examination (WLE) improved the ability to detect OPLs/OCs. Sixty high-risk patients, with suspicious oral lesions or recently diagnosed untreated OPLs/OCs, underwent sequential surveillance with WLE and AFV. Biopsies were obtained from all suspicious areas identified on both examinations (n = 189) and one normal-looking control area per person (n = 60). Sensitivity, specificity, and predictive values were calculated for WLE, AFV, and WLE + AFV. Estimates were calculated separately for lesions classified by histopathologic grades as low-grade lesions, high-grade lesions (HGL), and OCs. Sequential surveillance with WLE + AFV provided a greater sensitivity than WLE in detecting low-grade lesions (75% versus 44%), HGLs (100% versus 71%), and OCs (100% versus 80%). The specificity in detecting OPLs/OCs decreased from 70% with WLE to 38% with WLE + AFV. Thirteen of the 76 additional biopsies (17%) obtained based on AFV findings were HGLs/OCs. Five patients (8%) were diagnosed with a HGL/OC only because of the addition of AFV to WLE. In seven patients, additional HGL/OC foci or wider OC margins were detected on AFV. Additionally, AFV aided in the detection of metachronous HGL/OC in 6 of 26 patients (23%) with a history of previously treated head and neck cancer. Overall, the addition of AFV to WLE improved the ability to detect HGLs/OCs. In spite of the lower specificity, AFV + WLE can be a highly sensitive first-line surveillance tool for detecting OPLs/OCs in high-risk patients.
PMCID: PMC3653312  PMID: 19892665
15.  Genome-Wide Association Study of Serum Selenium Concentrations 
Nutrients  2013;5(5):1706-1718.
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.
PMCID: PMC3708345  PMID: 23698163
selenium; serum; selenoprotein; genome-wide association study; AGA; NEIL3; SLC39A11
16.  Accuracy of Self-Reported Tobacco Assessments in a Head and Neck Cancer Treatment Population 
Radiotherapy and Oncology  2011;103(1):45-48.
Prospective analysis was performed of self-reported and biochemically confirmed tobacco use in 50 head and neck cancer patients during treatment. With 93.5% compliance to complete weekly self-report and biochemical confirmatory tests, 29.4% of smokers required biochemical assessment for identification. Accuracy increased by 14.9% with weekly vs. baseline self-reported assessments. Data confirm that head and neck cancer patients misrepresent true tobacco use during treatment.
PMCID: PMC3327779  PMID: 22119370
tobacco; smoking; head/neck; radiotherapy; cotinine
Coffee has been hypothesized to have pro- and anti-carcinogenic properties, while tea may contain anti-carcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, while findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (abbreviated as SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous.
In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model.
No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR=1.10, 95% CI=0.81-1.48 comparing ≥900 to <0g/day; 237g≈8oz), tea (MVRR=0.96, 95% CI=0.78-1.16 comparing ≥400 to 0g/day; 237g≈8oz) or SSB (MVRR=1.19, 95% CI=0.98-1.46 comparing ≥250 to 0g/day; 355g≈12oz) (p-value, test for between-studies heterogeneity >0.05). These associations were consistent across levels of sex, smoking status and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR=1.06, 95% CI=1.02-1.12).
Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.
PMCID: PMC3275675  PMID: 22194529
Pancreatic Cancer; Beverages; Pooled Analysis
18.  Folate Intake and Risk of Pancreatic Cancer: Pooled Analysis of Prospective Cohort Studies 
Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies.
We analyzed primary data from 14 prospective cohort studies that included 319 716 men and 542 948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided.
During 7–20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, Ptrend = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, Ptrend = .90). No between-study heterogeneity was observed (for dietary folate, Pheterogeneity = .15; for total folate, Pheterogeneity = .22).
Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
PMCID: PMC3243674  PMID: 22034634
19.  Individual-Level Factors in Colorectal Cancer Screening: A Review of the Literature on the Relation of Individual-Level Health Behavior Constructs and Screening Behavior 
Psycho-Oncology  2010;20(10):1023-1033.
Compliance with colorectal cancer screening recommendations requires considerable conscious effort on the part of the individual patient, making an individual's decisions about engagement in screening an important contributor to compliance or noncompliance. The objective of this paper was to examine the effectiveness of individual-level behavior theories and their associated constructs in accounting for engagement in colorectal cancer screening behavior. We reviewed the literature examining constructs from formal models of individual-level health behavior as factors associated with compliance with screening for colorectal cancer. All published studies examining one or more constructs from the health belief model, theory of planned behavior, transtheoretical model, or social cognitive theory and their relation to screening behavior or behavioral intentions were included in the analysis. By and large, results of studies supported the theory-based predictions for the influence of constructs on cancer screening behavior. However, the evidence base for many of these relations, especially for models other than the health belief model, is quite limited. Suggestions are made for future research on individual-level determinants of colorectal cancer screening.
PMCID: PMC3038178  PMID: 21954045
colorectal cancer screening; decision making; individual adherence; literature review
Epidemiologic studies of pancreatic cancer risk have reported null or non-significant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently.
A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model.
Compared to individuals with a body mass index (BMI) at baseline between 21–22.9kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI≥30kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI=1.09–1.56 comparing BMI≥25kg/m2 to a BMI between 21–22.9kg/m2). Compared to individuals who were not overweight in early adulthood (BMI<25kg/m2) and not obese at baseline (BMI<30kg/m2), pancreatic cancer risk was 54% higher (95%CI=24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥10kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR=1.35 comparing the highest versus lowest quartile, 95%CI=1.03–1.78).
BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
PMCID: PMC3073156  PMID: 21105029
Pancreatic Cancer; Anthropometry; Pooled Analysis
21.  PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells 
Oncogene  2011;31(12):1484-1492.
Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here, we report that C-MYC in cells from several randomly chosen melanoma lines was up-regulated at the protein level, and largely due to the increased protein stability. Of all known regulators of C-MYC stability, levels of B56α subunit of the PP2A tumor suppressor complex were substantially suppressed in all human melanoma cells compared to normal melanocytes. Accordingly, immuno-histochemical analysis revealed that the lowest and the highest amounts of PP2A-B56α were predominantly detected in metastatic melanoma tissues and in primary melanomas from patients with good clinical outcome, respectively. Importantly, PP2A-B56α overexpression suppressed C-MYC in melanoma cells and induced OIS, whereas depletion of PP2A-B56α in normal human melanocytes up-regulated C-MYC protein levels and suppressed BRAFV600E- and, less efficiently, NRASQ61R-induced senescence. Our data reveal a mechanism of C-MYC overexpression in melanoma cells and identify a functional role for PP2A-B56α in OIS of melanocytic cells.
PMCID: PMC3213274  PMID: 21822300
PP2A-B56α; C-MYC; melanoma; senescence
22.  Consistent Implementation of Decisions in the Brain 
PLoS ONE  2012;7(9):e43443.
Despite the complexity and variability of decision processes, motor responses are generally stereotypical and independent of decision difficulty. How is this consistency achieved? Through an engineering analogy we consider how and why a system should be designed to realise not only flexible decision-making, but also consistent decision implementation. We specifically consider neurobiologically-plausible accumulator models of decision-making, in which decisions are made when a decision threshold is reached. To trade-off between the speed and accuracy of the decision in these models, one can either adjust the thresholds themselves or, equivalently, fix the thresholds and adjust baseline activation. Here we review how this equivalence can be implemented in such models. We then argue that manipulating baseline activation is preferable as it realises consistent decision implementation by ensuring consistency of motor inputs, summarise empirical evidence in support of this hypothesis, and suggest that it could be a general principle of decision making and implementation. Our goal is therefore to review how neurobiologically-plausible models of decision-making can manipulate speed-accuracy trade-offs using different mechanisms, to consider which of these mechanisms has more desirable decision-implementation properties, and then review the relevant neuroscientific data on which mechanism brains actually use.
PMCID: PMC3440404  PMID: 22984425
23.  Tobacco sales in pharmacies: a survey of attitudes, knowledge and beliefs of pharmacists employed in student experiential and other worksites in Western New York 
BMC Research Notes  2012;5:413.
Pharmacies are venues in which patients seek out products and professional advice in order to improve overall health. However, many pharmacies in the United States continue to sell tobacco products, which are widely known to cause detrimental health effects. This conflict presents a challenge to pharmacists, who are becoming increasingly more involved in patient health promotion activities. This study sought to assess Western New York (WNY) area pharmacists’ opinions about the sale of tobacco products in pharmacies, and pharmacists’ opinions on their role in patient smoking cessation.
Participants responded to two parallel surveys; a web-based survey was completed by 148 university-affiliated pharmacist preceptors via a list based sample, and a mail-based survey was completed by the supervising pharmacist in 120 area pharmacies via a list-based sample. The combined response rate for both surveys was 31%. Univariate and bivariate analyses were performed to determine any significant differences between the preceptor and supervising pharmacist survey groups.
Over 75% of respondents support legislation banning the sale of tobacco products in pharmacies. Over 86% of respondents would prefer to work in a pharmacy that does not sell tobacco products. Differences between preceptor and supervising pharmacist groups were observed. Action regarding counseling patients was uncommon among both groups.
Pharmacists support initiatives that increase their role in cessation counseling and initiatives that restrict the sale of tobacco products in pharmacies. These data could have important implications for communities and pharmacy practice.
PMCID: PMC3492148  PMID: 22867129
Tobacco sales; Pharmacists; Preceptors; Public health policy; Survey research; Pharmacies
24.  Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis 
A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.
We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from four studies (total 3891 cases, 4490 controls): the Women’s Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions.
SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI 1.01–1.40; p-trend 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI 0.99–1.25; p-trend 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of seventeen studies (including these four) gave an OR per A allele of 1.07 (95% CI 1.03–1.12; p-trend 0.001).
Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.
If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia.
PMCID: PMC3005543  PMID: 20978172
colorectal; adenoma; cancer; 9p24; rs719725
25.  Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies 
Cancer causes & control : CCC  2010;21(11):1745-1757.
To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer.
Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model.
Among 676,141 men and women, 5,454 colon cancer cases were identified (7–20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76–1.02, >4,000 vs. ≤1,000 μg/day) for vitamin A, 0.81 (0.71–0.92, >600 vs. ≤100 mg/day) for vitamin C, and 0.78 (0.66–0.92, >200 vs. ≤6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81–0.96).
Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.
PMCID: PMC3091388  PMID: 20820901
Vitamin A; Vitamin C; Vitamin E; Multivitamin; Colon cancer; Cohort study; Pooled analysis

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