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BackgroundPrevious epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies.ObjectivesTo evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure.MethodsBasal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only.ResultsThere was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs.ConclusionsOverall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC.

The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH-AARP Diet and Health Study (1995-2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked < or =1 or >1 pack/day and for current smokers who smoked < or =1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Previous studies have provided limited evidence for a harmful effect of high glycemic index and dietary glycemic load on cancer. The authors analyzed associations among glycemic index, glycemic load, and risk of cancer in women and men in the National Institutes of Health-AARP Diet and Health Study. Published glycemic index values were assigned to 225 foods/food groups. Glycemic load was calculated by multiplying the glycemic index, carbohydrate content, and intake frequency of individual foods reported on a food frequency questionnaire. From 1995 through 2003, the authors identified 15,215 and 33,203 cancer cases in women and men, respectively. Cox proportional hazards models were used to estimate multivariate relative risks and 95% confidence intervals. For women and men, respectively, the relative risks for total cancer for high versus low glycemic index were 1.03 (P(trend)=0.217) and 1.04 (P(trend)=0.012) and, for glycemic load, were 0.90 (P(trend)=0.024) and 0.93 (P(trend)=0.01). Associations with total cancer held only among the overweight for glycemic index and among those of healthy weight for glycemic load. These findings suggest that glycemic index and glycemic load are not strong predictors of cancer incidence. The direction and small magnitude of associations might be explained by the manner in which high glycemic index and glycemic load track with overall diet and lifestyle patterns. [ABSTRACT FROM AUTHOR]

An increasing number of men and women are being diagnosed with cancer and many cancer survivors are seeking lifestyle-based approaches to improve survival. The American Cancer Society issued nutrition and physical activity recommendations for cancer survivors in 2006. This article discusses these guidelines, including more recent publications regarding obesity, exercise, diet, and nutrient supplement use in relation to cancer outcomes including survival. Observational data strongly indicate that obesity, weight gain, and physical inactivity are adverse prognostic factors, although data on diet or supplement use in relation to cancer survival are more limited and inconsistent. Randomized trials of lifestyle interventions in survivors are also very limited at present. Although there are major research gaps in the literature on nutrition and physical activity for cancer survivors, the available evidence to date suggests that physicians should be familiar with current guidelines and discuss them with their patients as an important strategy to improve long-term survival. [ABSTRACT FROM AUTHOR]

Because little is known about the etiology of non-Hodgkin lymphoma (NHL), a heterogeneous disease, and because dietary factors are modifiable, the authors examined the associations between nutrients related to one-carbon metabolism and risk of NHL in a population-based case-control study of Connecticut women diagnosed between 1996 and 2000. A total of 594 cases and 710 controls completed a food frequency questionnaire for determination of intakes of folate, vitamins B(2), B(6), and B(12), and methionine. Through unconditional logistic regression, the authors estimated the risk of NHL associated with intake of each nutrient. Comparing the highest quartile of intake with the lowest, the authors found lower risks of all NHL associated with increasing intakes of folate and methionine. Analysis by NHL subtype indicated lower risks of diffuse large B-cell lymphoma (highest quartile vs. lowest: odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30, 0.98; p-trend = 0.02) and marginal zone lymphoma (highest quartile vs. lowest: OR = 0.08, 95% CI: 0.02, 0.26; p-trend < 0.0001) associated with folate. Vitamin B(6) intake was also associated with lower risk of NHL overall and of marginal zone lymphoma (highest quartile vs. lowest: OR = 0.23, 95% CI: 0.08, 0.65; p-trend = 0.002). These findings suggest that these nutrients may be important for susceptibility to NHL. [ABSTRACT FROM AUTHOR]

Supplemental beta-carotene has been shown to increase lung cancer risk in recent chemoprevention trials, especially in current smokers. Several possible mechanisms for this effect have been suggested based upon in vitro and animal studies, but mechanistic data from human studies to explain the excess risk are lacking. beta-Carotene has both antioxidant and prooxidant effects in vitro; therefore, we evaluated whether or not high-dose supplemental beta-carotene might have prooxidant effects in vivo, especially in current smokers taking high-dose supplemental beta-carotene for several years (median 4.0 yr). Urine samples (n = 55 total) were collected from both smokers and nonsmokers participating in a multiyear randomized chemoprevention trial of supplemental beta-carotene (50 mg/day) versus placebo. Samples were analyzed by GC/MS for total isoprostanes and for 8-iso-prostaglandin F2 (8-iso-PGF2), stable end products of lipid peroxidation in vivo. Smokers had higher levels of both total isoprostanes and 8-iso-PGF2. Smokers and nonsmokers randomized to beta-carotene had nonsignificantly lower concentrations of total isoprostanes and of 8-iso-PGF2 [mean +- SD 8-iso-PGF2/ml = 2.00 +- 1.72 (placebo smoker); 1.72 +- 1.66 (beta-carotene smoker); 1.22 +- 0.68 (placebo nonsmoker); 0.97 +- 0.62 (beta-carotene nonsmoker)]. These results indicate that supplemental beta-carotene, even when given at high doses for many years, does not have prooxidant effects in either smokers or nonsmokers, as measured by urinary excretion of F2-isoprostanes. [ABSTRACT FROM AUTHOR]

Background: Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study.Methods: We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation.Results: Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%).Conclusion: In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables. [ABSTRACT FROM AUTHOR]

High doses of beta-carotene, a lipid-soluble nutrient, may affect the plasma concentrations of other lipid-soluble nutrients. The purpose of this study was to assess the effects of long-term daily supplementation with beta-carotene (50 mg/d) on circulating concentrations of other carotenoids, retinol, and alpha-tocopherol over time. Data were available from 259 men and women participating in the Carotene Prevention Trial, a 2-center chemoprevention trial designed to determine whether supplemental beta-carotene can prevent second malignant tumors in patients cured of an early stage cancer of the oral cavity, pharynx, or larynx. Up to 2 blood samples were obtained before the intervention (before and after a 1-mo placebo run-in), with postrandomization samples obtained at 3, 12, 24, 36, 48, and 60 mo. Supplementation with beta-carotene produced a persistent 9- to 10-fold increase in median plasma beta-carotene concentrations (225 nmol/L at baseline to 2255 nmol/L at 3 mo) and a persistent 2-fold increase in median plasma alpha-carotene concentrations (45 nmol/L at baseline to 95 nmol/L at 3 mo). Concentrations of retinol, alpha-tocopherol, lycopene, and lutein/zeaxanthin were not affected by supplemental beta-carotene. Up to 5 y of daily supplementation with beta-carotene increased circulating concentrations of alpha- and beta-carotene, but did not alter concentrations of lycopene, lutein/zeaxanthin, retinol, or alpha-tocopherol. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Abstract Background The Institute of Medicine has prioritized shared decision making (SDM), yet little is known about the impact of SDM over time on behavioral outcomes for children. This study examined the longitudinal association of SDM with behavioral impairment among children with special health care needs (CSHCN). Method CSHCN aged 5-17 years in the 2002-2006 Medical Expenditure Panel Survey were followed for 2 years. The validated Columbia Impairment Scale measured impairment. SDM was measured with 7 items addressing the 4 components of SDM. The main exposures were (1) the mean level of SDM across the 2 study years and (2) the change in SDM over the 2 years. Using linear regression, we measured the association of SDM and behavioral impairment. Results Among 2,454 subjects representing 10.2 million CSHCN, SDM increased among 37% of the population, decreased among 36% and remained unchanged among 27%. For CSHCN impaired at baseline, the change in SDM was significant with each 1-point increase in SDM over time associated with a 2-point decrease in impairment (95% CI: 0.5, 3.4), whereas the mean level of SDM was not associated with impairment. In contrast, among those below the impairment threshold, the mean level of SDM was significant with each one point increase in the mean level of SDM associated with a 1.1-point decrease in impairment (0.4, 1.7), but the change was not associated with impairment. Conclusion Although the change in SDM may be more important for children with behavioral impairment and the mean level over time for those below the impairment threshold, results suggest that both the change in SDM and the mean level may impact behavioral health for CSHCN.

BACKGROUND: Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype. METHODS: We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15 175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% CI from unconditional logistic regression models, controlling for study centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random-effects logistic regression, and by calculation of Wald chi(2) statistics. FINDINGS: People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0.83 [95% CI 0.76-0.89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0.73 [0.64-0.84] vs 0.95 [0.80-1.14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitt's lymphoma (0.51 [0.33-0.77]). INTERPRETATION: People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association. [ABSTRACT FROM AUTHOR]

Ultra-processed food consumption has increased worldwide, but associations with cancer risk remain unclear and potential underlying mechanisms are speculative. A robust, multidisciplinary, research agenda is needed to address current research limitations and gaps., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Purpose: HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case-control study in Connecticut, New Jersey and part of New York City., Methods: Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors., Results: The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2-204) and 2.13 (95% CI 1.52-3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls., Conclusions: Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

Background: There are few prospective studies comparing race-specific associations between diet, nutrients, and health-related parameters, and prostate cancer risk., Methods: Race-specific prostate cancer risk associations were examined among men in the National Institutes of Health (NIH)-AARP Diet and Health Study. We identified 1417 cases among black men (209 advanced), and 28,845 among white men (3898 advanced). Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). We also evaluated the cumulative change in the HR for black race following adjustment for each factor., Results: Race-specific prostate cancer associations were similar in black and white men across disease subtypes only for history of diabetes (overall : HR = 0.77, 95% CI: 0.65-0.90 and HR = 0.72, 95% CI: 0.69-0.76, respectively; P interaction  = 0.66). By contrast, there was a positive risk association with height for white men  and  inverse for black men (P interaction : non-advanced = 0.01; advanced = 0.04). This difference remained among men with at least 2 years of follow-up for non-advanced (P interaction  = 0.01), but not advanced disease (P interaction  = 0.24); or after adjustment for prostate cancer screening (non-advanced P interaction  = 0.53, advanced P interaction  = 0.31). The only other evidence of interaction with race was observed for dietary vitamin D intake and non-advanced disease, but only after adjustment for screening (P interaction  = 0.02). Cumulative adjustment for each factor increased the HR for black race by 32.9% for overall cancer and 12.4% for advanced disease., Conclusions: Our data suggest few of the dietary, nutrient, and health-related factors associated with prostate cancer risk in predominantly non-Hispanic white men were associated with risk in black men, and adjustment for these factors widen the black-white difference in risk. Larger studies of black men, particularly with prospective data, are needed to help identify risk factors relevant to this population.

Background: The epidemiologic evidence for associations between dietary factors and breast cancer is weak and etiologic mechanisms are often unclear. Exploring the role of dietary biomarkers with metabolomics can potentially facilitate objective dietary characterization, mitigate errors related to self-reported diet, agnostically test metabolic pathways, and identify mechanistic mediators. Objective: The aim of this study was to evaluate associations of diet-related metabolites with the risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Design: We examined prediagnostic serum concentrations of diet-related metabolites in a nested case-control study in 621 postmenopausal invasive breast cancer cases and 621 matched controls in the multicenter PLCO cohort. We calculated partial Pearson correlations between 617 metabolites and 55 foods, food groups, and vitamin supplements on the basis of the 2015 Dietary Guidelines for Americans and derived from a 137-item self-administered food-frequency questionnaire. Diet-related metabolites ( P- correlation < 1.47 × 10 -6 ) were evaluated in breast cancer analyses. ORs for the 90th compared with the 10th percentile were calculated by using conditional logistic regression, with body mass index, physical inactivity, other breast cancer risk factors, and caloric intake controlled for (false discovery rate <0.2). Results: Of 113 diet-related metabolites, 3 were associated with overall breast cancer risk (621 cases): caprate (10:0), a saturated fatty acid (OR: 1.77; 95% CI = 1.28, 2.43); γ-carboxyethyl hydrochroman (γ-CEHC), a vitamin E (γ-tocopherol) derivative (OR: 1.64; 95% CI: 1.18, 2.28); and 4-androsten-3β,17β-diol-monosulfate (1), an androgen (OR: 1.61; 95% CI: 1.20, 2.16). Nineteen metabolites were significantly associated with estrogen receptor (ER)-positive (ER + ) breast cancer (418 cases): 12 alcohol-associated metabolites, including 7 androgens and α-hydroxyisovalerate (OR: 2.23; 95% CI: 1.50, 3.32); 3 vitamin E (tocopherol) derivatives (e.g., γ-CEHC; OR: 1.80; 95% CI: 1.20, 2.70); butter-associated caprate (10:0) (OR: 1.81; 95% CI: 1.23, 2.67); and fried food-associated 2-hydroxyoctanoate (OR: 1.46; 95% CI: 1.03, 2.07). No metabolites were significantly associated with ER-negative breast cancer (144 cases). Conclusions: Prediagnostic serum concentrations of metabolites related to alcohol, vitamin E, and animal fats were moderately strongly associated with ER + breast cancer risk. Our findings show how nutritional metabolomics might identify diet-related exposures that modulate cancer risk. This trial was registered at clinicaltrials.gov as NCT00339495., (© 2017 American Society for Nutrition.)

Background: Few studies have prospectively examined the relationship between vitamin D status and prostate cancer risk in black men, a group at high risk for both low vitamin D status and prostate cancer., Methods: Among black men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we identified 226 prostate cancer cases and 452 controls matched on age at randomization (±5 years), date of blood draw (±30 days), calendar year of cohort entry, and time since baseline prostate cancer screening (±1 year). Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between serum 25-hydroxyvitamin D [25(OH)D], vitamin D binding protein (DBP), the 25(OH)D:DBP molar ratio, and prostate cancer risk., Results: Serum 25(OH)D was not associated with overall prostate cancer (Q4 vs Q1: OR, 0.73; 95% CI, 0.40-1.33; P for trend = .25), although there were apparent inverse associations for nonaggressive disease (global P = .03, clinical stage I/II, and Gleason score <7) and among men ≥62 years old (P for interaction = .04) that were restricted to Q3. Interestingly, serum DBP was significantly inversely associated with prostate cancer risk (Q4 vs Q1: OR, 0.45; 95% CI, 0.20-1.00; P for trend = .03), whereas the 25(OH)D:DBP molar ratio was not. Results were similar when we mutually adjusted for 25(OH)D and DBP, and we found no evidence of interaction between the two., Conclusion: Our study suggests higher (versus lower) circulating DBP may be independently associated with a decreased prostate cancer risk in black men independent of 25(OH)D status. Cancer 2017;123:2698-704. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Growing evidence suggests that some individuals may exhibit symptoms of dependence on ultraviolet (UV) light, a known carcinogen, in the context of tanning; however, few studies have investigated predictors of tanning dependence (TD)., Objective: To identify predictors of TD., Methods: Non-Hispanics of European ancestry who had previously participated in a case-control study of early-onset basal cell carcinoma completed an online survey to ascertain TD and other behaviours (alcohol dependence, nicotine dependence, seasonal affective disorder (SAD), exercise 'addiction' and depression). Information on host factors, such as skin and eye colour and history of sunbathing and indoor tanning, was obtained from a study in which the participants were previously enrolled. Lifetime TD was assessed using the modified Cut down, Annoyed, Guilty, Eye-opener (mCAGE) and the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (mDSM-IV-TR) questionnaires. Participants were classified as 'TD' if positive on both questionnaires and not TD if negative on both questionnaires., Results: In total, 499 individuals completed the online survey (81.9% participation rate), and 24.4% were classified as 'TD'. In the multivariate model, women were more likely to be TD [odds ratio (OR) 6.93; 95% confidence intervals (95% CI) (3.36-14.27)] than men. Alcohol dependence (OR 6.55: 95% CI 3.19-13.42), SAD (OR 2.77; 95% CI 1.26-6.09) and exercise 'addiction' (OR 5.47; 95% CI 1.15-26.06) were all significant predictors for TD., Conclusion: Increased knowledge of those at risk for TD will allow appropriate interventions to be designed., (© 2017 European Academy of Dermatology and Venereology.)

Background: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings., Methods: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake., Results: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53-0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62-0.99), fish (HR=0.74, 95% CI: 0.57-0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59-0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01-1.65, P-trend=0.03)., Conclusions: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

Background: Healthy dietary patterns that conform to national dietary guidelines are related to lower chronic disease incidence and longer life span. However, the precise mechanisms involved are unclear. Identifying biomarkers of dietary patterns may provide tools to validate diet quality measurement and determine underlying metabolic pathways influenced by diet quality., Objective: The objective of this study was to examine the correlation of 4 diet quality indexes [the Healthy Eating Index (HEI) 2010, the Alternate Mediterranean Diet Score (aMED), the WHO Healthy Diet Indicator (HDI), and the Baltic Sea Diet (BSD)] with serum metabolites., Design: We evaluated dietary patterns and metabolites in male Finnish smokers (n = 1336) from 5 nested case-control studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Participants completed a validated food-frequency questionnaire and provided a fasting serum sample before study randomization (1985-1988). Metabolites were measured with the use of mass spectrometry. We analyzed cross-sectional partial correlations of 1316 metabolites with 4 diet quality indexes, adjusting for age, body mass index, smoking, energy intake, education, and physical activity. We pooled estimates across studies with the use of fixed-effects meta-analysis with Bonferroni correction for multiple comparisons, and conducted metabolic pathway analyses., Results: The HEI-2010, aMED, HDI, and BSD were associated with 23, 46, 23, and 33 metabolites, respectively (17, 21, 11, and 10 metabolites, respectively, were chemically identified; r-range: -0.30 to 0.20; P = 6 × 10 -15 to 8 × 10 -6 ). Food-based diet indexes (HEI-2010, aMED, and BSD) were associated with metabolites correlated with most components used to score adherence (e.g., fruit, vegetables, whole grains, fish, and unsaturated fat). HDI correlated with metabolites related to polyunsaturated fat and fiber components, but not other macro- or micronutrients (e.g., percentages of protein and cholesterol). The lysolipid and food and plant xenobiotic pathways were most strongly associated with diet quality., Conclusions: Diet quality, measured by healthy diet indexes, is associated with serum metabolites, with the specific metabolite profile of each diet index related to the diet components used to score adherence. This trial was registered at clinicaltrials.gov as NCT00342992., (© 2017 American Society for Nutrition.)

Introduction: Basal cell carcinoma (BCC) is the most common malignancy in the US. Body mass index (BMI) and height have been associated with a variety of cancer types, yet the evidence regarding BCC is limited. Therefore, we evaluated BMI and height in relation to early-onset BCC (under age 40) and explored the potential role of ultraviolet (UV) radiation exposure and estrogen-related exposures in the BMI-BCC relationship., Methods: BCC cases (n=377) were identified through a central dermatopathology facility in Connecticut. Control subjects (n=389) with benign skin conditions were randomly sampled from the same database and frequency matched to cases on age (median=36, interquartile range 33-39), gender, and biopsy site. Participants reported weight (usual adult and at age 18), adult height, sociodemographic, phenotypic, and medical characteristics, and prior UV exposures. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models., Results: Adult BMI was inversely associated with early-onset BCC (obese vs. normal OR=0.43, 95% CI=0.26-0.71). A similar inverse association was present for BMI at age 18 (OR=0.54, 95% CI=0.34-0.85). Excluding UV exposures from the BMI models and including estrogen-related exposures among women only did not alter the association between BMI and BCC, indicating limited mediation or confounding. We did not observe an association between adult height and BCC (OR per cm=1.00, 95% CI=0.98-1.02)., Conclusions: We found a significant inverse association between BMI and early-onset BCC, but no association between height and BCC. This association was not explained by UV exposures or estrogen-related exposures in women., Competing Interests: None, (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Diet plays an important role in chronic disease etiology, but some diet-disease associations remain inconclusive because of methodologic limitations in dietary assessment. Metabolomics is a novel method for identifying objective dietary biomarkers, although it is unclear what dietary information is captured from metabolites found in serum compared with urine., Objective: We compared metabolite profiles of habitual diet measured from serum with those measured from urine., Design: We first estimated correlations between consumption of 56 foods, beverages, and supplements assessed by a food-frequency questionnaire, with 676 serum and 848 urine metabolites identified by untargeted liquid chromatography mass spectrometry, ultra-high performance liquid chromatography tandem mass spectrometry, and gas chromatography mass spectrometry in a colon adenoma case-control study (n = 125 cases and 128 controls) while adjusting for age, sex, smoking, fasting, case-control status, body mass index, physical activity, education, and caloric intake. We controlled for multiple comparisons with the use of a false discovery rate of <0.1. Next, we created serum and urine multiple-metabolite models to predict food intake with the use of 10-fold crossvalidation least absolute shrinkage and selection operator regression for 80% of the data; predicted values were created in the remaining 20%. Finally, we compared predicted values with estimates obtained from self-reported intake for metabolites measured in serum and urine., Results: We identified metabolites associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were correlated with ≥1 food, beverage, or supplement. More metabolites in urine (n = 154) than in serum (n = 39) were associated uniquely with one food. We found previously unreported metabolite associations with leafy green vegetables, sugar-sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and wine. Prediction of dietary intake from multiple-metabolite profiles was similar between biofluids., Conclusions: Candidate metabolite biomarkers of habitual diet are identifiable in both serum and urine. Urine samples offer a valid alternative or complement to serum for metabolite biomarkers of diet in large-scale clinical or epidemiologic studies., (© 2016 American Society for Nutrition.)

Despite the potentially important roles of diet and nutrition in cancer prevention, the evidence to support these roles is widely perceived by the public and health professionals as being inconsistent. In this Review, we present the issues and challenges in conducting and interpreting diet-cancer research, including those relating to the design of epidemiological studies, dietary data collection methods, and factors that affect the outcome of intervention trials. Approaches to improve effect estimates, such as the use of biomarkers to improve the accuracy of characterizing dietary exposures, are also discussed. Nutritional and dietary patterns are complex; therefore, the use of a reductionist approach to investigations, by focusing on specific nutrients, can produce misleading information. The effects of tumour heterogeneity and the failure to appreciate the nonlinear, U-shaped relationship between micronutrients and cancer in both observational studies and clinical trials are discussed. New technologies and investigational approaches are enabling the exploration of complex interactions between genetic, epigenetic, metabolic, and gut-microbial processes that will inform our knowledge of the diet-cancer relationship. Communicating the status of the evolving science in the context of the overall scientific evidence base, and evidence-based dietary recommendations for cancer prevention, should be emphasized in guidance for the public and for individual patients.

Alcohol is a known carcinogen that may be associated with colorectal cancer. However, most epidemiologic studies assess alcoholic beverage consumption using self-reported data, leading to potential exposure misclassification. Biomarkers of alcohol consumption may provide an alternative, complementary approach that reduces misclassification and incorporates individual differences in alcohol metabolism. Therefore, we evaluated the relationship between previously identified alcohol consumption-related metabolites and colorectal cancer and adenoma using serum metabolomics data from two studies. Data on colorectal cancer were obtained from a nested case-control study of 502 US adults (252 cases, 250 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Data on colorectal adenoma were obtained from a case-control study of 197 US adults (120 cases, 77 controls) from the Navy Colon Adenoma Study. Unconditional multivariable logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) for eight alcohol consumption-related metabolites identified in a previous analysis: ethyl glucuronide; 4-androstene-3beta,17beta-diol disulfate 1; 5-alpha-androstan-3beta,17beta-diol disulfate; 16-hydroxypalmitate; bilirubin (E,Z or Z,E); cyclo (-leu-pro); dihomo-linoleate (20:2n6); and palmitoleate (16:1n7). We found no clear association between these alcohol consumption-related metabolites and either endpoint. However, we did observe an inverse association between cyclo (-leu-pro) and colorectal adenoma that was only observed in the highest metabolite quantile (OR 4th vs. 1st Quantile = 0.30, 95% CI: 0.12-0.78; P-trend = 0.047), but no association for colorectal cancer. In conclusion, there were no adverse associations between alcohol consumption-related metabolites and colorectal cancer or adenoma.

Alcohol is a carcinogen suspected of increasing lung cancer risk. Therefore, we prospectively evaluated the relationship between alcohol consumption and lung carcinoma in 492,902 persons from the National Institutes of Health-AARP Diet and Health Study. We used Cox models to calculate hazard ratios and 95% confidence intervals, adjusting for tobacco smoking and other potential confounders. Between 1995/1996 and December 31, 2006, there were 10,227 incident cases of lung carcinoma, classified as adenocarcinoma (n = 4,036), squamous cell carcinoma (n = 1,998), small cell carcinoma (n = 1,524), undifferentiated carcinoma (n = 559), and other (n = 2,110). Compared with nondrinking, alcohol consumption was associated with a modest nonlinear reduction in total lung carcinoma risk at lower levels of consumption (for 0.5-<1 drink/day, HR = 0.89, 95% confidence interval: 0.82, 0.96) but a modest increase in risk in the highest category (for ≥7 drinks/day, HR = 1.11, 95% confidence interval: 1.00, 1.24). Regarding histological type, alcohol was associated with a nonlinear reduction in squamous cell carcinoma that became attenuated as consumption increased and a modest increase in adenocarcinoma among heavier drinkers. Cubic spline models confirmed these findings. Our data suggest that the relationship between alcohol consumption and lung carcinoma differs by histological subtype., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC)., Materials and Methods: Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R., Results: A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35)., Conclusions: Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Feasible, valid, and reliable tools are needed to assess dietary quality among preschoolers. We aimed to test construct-/criterion-related validity and reliability of a dietary quality index generated from a liking survey and novel dietary patterns for characterizing food hedonism and parental feeding practices., Methods: Participants included 416 economically disadvantaged, diverse preschoolers (41% overweight/obese) from educational centers and their parents. Parents completed liking and frequency surveys; the liking survey took half as long to complete. Preschoolers' skin carotenoid status (measured by Resonance Raman spectroscopy) and BMI percentile (measured weight/height) were assessed. The Healthy Eating Preference Index (HEPI) was constructed from weighted averages of liking scores for food groups and healthy variety score and Healthy Eating Index 2010 (HEI) from nutrient analysis of the frequency survey., Results: The HEPI was normally distributed and showed construct validity and adequate internal reliability. In hierarchical regression analyses, the HEPI explained carotenoid status and adiposity as alternative or value-added predictors to HEI, supporting criterion-related validity of HEPI. Parental reporting of children's liking of high-fat/sweet/salty foods in excess of pleasurable activities (food hedonism) predicted heavier preschoolers, as did discord between HEI and HEPI (potential parental pressure toward healthy eating). HEPI alone or with HEI explained variability in carotenoid status and adiposity in path models with adequate to good fits., Conclusions: With simple collection and processing, the liking survey can generate a valid/reliable dietary quality index in child care settings to identify preschoolers at risk for lower nutritional status. Using liking and frequency-based screeners could improve understanding of parental feeding behaviors and precision of predicting nutritional status.

Background: Coffee drinking has been inversely associated with mortality as well as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin sensitivity and reduced inflammation are among the hypothesized mechanisms by which coffee drinking may affect cancer risk; however, associations between coffee drinking and systemic levels of immune and inflammatory markers have not been well characterized., Methods: We used Luminex bead-based assays to measure serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic Whites. Usual coffee intake was self-reported using a food frequency questionnaire. We used weighted multivariable logistic regression models to examine associations between coffee and dichotomized marker levels. We conducted statistical trend tests by modeling the median value of each coffee category and applied a 20% false discovery rate criterion to P values., Results: Ten of the 77 markers were nominally associated (P trend < 0.05) with coffee drinking. Five markers withstood correction for multiple comparisons and included aspects of the host response namely chemotaxis of monocytes/macrophages (IFNγ, CX3CL1/fractalkine, CCL4/MIP-1β), proinflammatory cytokines (sTNFRII), and regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating levels of IFNγ [odds ratios (OR), 0.35; 95% confidence intervals (CI), 0.16-0.75], CX3CL1/fractalkine (OR, 0.25; 95% CI, 0.10-0.64), CCL4/MIP-1β (OR, 0.48; 95% CI, 0.24-0.99), FGF-2 (OR, 0.62; 95% CI, 0.28-1.38), and sTNFRII (OR, 0.34; 95% CI, 0.15-0.79) than non-coffee drinkers., Conclusions: Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases., Impact: Validation studies, ideally controlled feeding trials, are needed to confirm these associations., (©2015 American Association for Cancer Research.)

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival., Methods: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively., Results: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide., Conclusions: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.

Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

Background: Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited., Methods: Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health-AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non-coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant., Results: The highest category of coffee intake was inversely associated with malignant melanoma (≥4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P trend = .01). This association was statistically significant for caffeinated (≥4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but not for decaffeinated coffee (P trend = .55)., Conclusions: Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted., (Published by Oxford University Press 2015.)

Background: Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based)., Objective: We sought to assess where individuals tanned indoors and skin cancer risk by tanning device location., Methods: Multivariate logistic regression was conducted in 2 US case-control studies of melanoma (1161 cases, 1083 controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382 controls, age<40 years) conducted between 2004 and 2010., Results: Most indoor tanners (86.4%-95.1%), especially younger individuals, tanned exclusively in businesses. Persons who used indoor tanning exclusively in businesses were at increased risk of melanoma (odds ratio 1.82, 95% confidence interval 1.47-2.26) and basal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48) compared with non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95% confidence interval 1.75-9.78); 67.6% used sun lamps., Limitations: Self-reported tanning and potential recall bias are limitations., Conclusion: Business-only tanning, despite claims of "safe" tanning, was positively associated with a significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon and mostly from sun lamps, which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)