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Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race.We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models.The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (ORObesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV(1))] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV(1) was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGA(ex)). We used mixed-effects linear regression modeling to examine the ∆vitE–FEV(1) association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P

Black women diagnosed with epithelial ovarian cancer have poorer survival compared to white women. Factors that contribute to this disparity, aside from socioeconomic status and guideline-adherent treatment, have not yet been clearly identified. We examined data from the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium which harmonized data on 1074 Black women and 3263 white women with ovarian cancer from seven US studies. We selected potential mediators and confounders by examining associations between each variable with race and survival. We then conducted a sequential mediation analysis using an imputation method to estimate total, direct, and indirect effects of race on ovarian cancer survival. Black women had worse survival than white women (HR = 1.30; 95% CI 1.16-1.47) during study follow-up; 67.9% of Black women and 69.8% of white women died. In our final model, mediators of this disparity include college education, nulliparity, smoking status, body mass index, diabetes, diabetes/race interaction, postmenopausal hormone (PMH) therapy duration, PMH duration/race interaction, PMH duration/age interaction, histotype, and stage. These mediators explained 48.8% (SE = 12.1%) of the overall disparity; histotype/stage and PMH duration accounted for the largest fraction. In summary, nearly half of the disparity in ovarian cancer survival between Black and white women in the OCWAA consortium is explained by education, lifestyle factors, diabetes, PMH use, and tumor characteristics. Our findings suggest that several potentially modifiable factors play a role. Further research to uncover additional mediators, incorporate data on social determinants of health, and identify potential avenues of intervention to reduce this disparity is urgently needed.

The purpose of this study was to investigate Healthy Eating Index 2015 (HEI-2015) and Energy-Adjusted Dietary Inflammatory Index (E-DIITM) scores in women’s cancer survivors and to examine socio-economic (SES) characteristics associated with these two diet indices. In this cross-sectional study, survivors of women’s cancers completed a demographic questionnaire and up to three 24-h dietary recalls. HEI-2015 and E-DII scores were calculated from average intakes. One-way ANOVA was used to examine the association of various demographic factors on HEI-2015 and E-DII scores. Pearson Correlation was used to calculate the correlation between the two scores. The average HEI-2015 score was 55.0 ± 13.5, lower than the national average, and average E-DII was −1.14 ± 2.24, with 29% of women having a more pro-inflammatory and 71% a more anti-inflammatory diet. Diets with higher HEI-2015 scores were associated with more anti-inflammatory diets (r = −0.67, p < 0.001). Those having a graduate degree (F(2,49) = 3.6, p = 0.03) and completing cancer treatment > 4 years ago (F(2,49) = 4.8, p = 0.01) had higher HEI-2015 scores. There were no associations between SES and E-DII scores. The diet quality of women’s cancer survivors is comparatively low, but many achieved an anti-inflammatory diet; a promising avenue for preventing recurrence. There is an urgent need to involve health care professionals in the guidance of women’s cancer survivors to improve diet quality and prevent cancer recurrence.

Background: Menstrual cycle characteristics—including age at menarche and cycle length— have been associated with ovarian cancer risk in White women. However, the associations between menstrual cycle characteristics and ovarian cancer risk among Black women have been sparsely studied. Methods: Using the Ovarian Cancer in Women of African Ancestry (OCWAA) Consortium that includes 1,024 Black and 2,910 White women diagnosed with epithelial ovarian cancer (EOC) and 2,325 Black and 7,549 White matched controls, we investigated associations between menstrual cycle characteristics (age at menarche, age at menstrual regularity, cycle length, and ever missing three periods) and EOC risk by race and menopausal status. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results: Black women were more likely to be Conclusions: Earlier age at menarche and cycle irregularity are associated with increased EOC risk for White but not Black women. Impact: Associations between menstrual cycle characteristics and EOC risk were not uniform by race.

BACKGROUND: Chronic inflammation is associated with ovarian carcinogenesis; yet, the impact of inflammatory-related exposures on outcomes has been understudied. OBJECTIVE: Given the poor survival of women diagnosed with ovarian cancer, especially African-Americans, we examined whether diet-associated inflammation, a modifiable source of chronic systemic inflammation measured by the dietary inflammatory index (DII), was associated with all-cause mortality among African-American women with ovarian carcinoma. METHODS: Data were available from 490 ovarian carcinoma patients enrolled in a population-based case-control study of African-American women with ovarian cancer, the African-American Cancer Epidemiology Study. Energy-adjusted DII (E-DII) scores were calculated based on prediagnostic dietary intake of foods alone or foods and supplements, which was self-reported using the 2005 Block Food Frequency Questionnaire. Cox proportional hazards regression was used to estimate risk of mortality overall and for the most common histotype, high-grade serous carcinoma. Additionally, we assessed interaction by age at diagnosis and smoking status. RESULTS: Women included in this study had a median age of 57 y, and the majority of women were obese (58%), had late-stage disease (Stage III or IV, 66%), and had high-grade serous carcinoma (64%). Greater E-DII scores including supplements (indicating greater inflammatory potential) were associated with an increased risk of mortality among women with high-grade serous carcinoma (HR(1-unit change): 1.08; 95% CI: 1.01, 1.17). Similar associations were observed for the E-DII excluding supplements, although not statistically significant (HR(1-unit change): 1.07; 95% CI: 0.97, 1.17). There was an interaction by smoking status, where the positive association with mortality was present only among ever smokers (HR(Quartile 4/Quartile 1): 2.36; 95% CI: 1.21, 4.60) but not among never smokers. CONCLUSIONS: Greater inflammatory potential of prediagnostic diet may adversely impact prognosis among African-American women with high-grade serous carcinoma, and specifically among ever smokers.

Background The transition to college is associated with weight gain, but the relation between eating behavior indicators and anthropometric outcomes during this period remains unclear. Objective We aimed to evaluate sex differences in stress, emotional eating, tendency to overeat, and restrained eating behavior, and determine whether the psycho-behavioral constructs assessed immediately prior to starting college are associated with anthropometry and adiposity at the start of college, and with first-semester weight gain. Methods A prospective study administered the Three Factor Eating Questionnaire (TFEQ), Satter Eating Competence Inventory, and Perceived Stress Scale (PSS) to 264 participants one month before college. Body composition was assessed via dual energy X-ray absorptiometry (DXA) at the start of college, and anthropometry (weight, height, waist circumference [WC]) was collected at the beginning and end of the first semester. Ordinary least squares regression tested the cross-sectional association of baseline psychological and behavioral scales with baseline DXA and anthropometry, and the longitudinal association with change in anthropometry. Results Among 264 participants, 91% (241) had baseline data, and 66% (173) completed follow-up. In sex-adjusted linear regression models, baseline TFEQ disinhibited and emotional (DE; EE) eating sub-scales were positively associated with baseline weight (P = 0.003; DE, P = 0.014; EE), body mass index (BMI, P = 0.002; DE, P = 0.001; EE), WC (P = 0.004; DE, P = 0.006; EE) and DXA fat mass index (P = 0.023; DE, P = 0.014; EE). Baseline PSS was positively associated with subsequent changes in weight and WC among males only (Pinteraction = 0.0268 and 0.0017 for weight and WC, respectively). Conclusion College freshmen with questionnaire scores indicating a greater tendency to overeat in response to external cues and emotions tended to have greater weight, BMI, and WC at the start of college. Males with higher perceived stress at college entrance subsequently gained significantly more weight in the first semester, but no such relation was evident in females.

Background: Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. Methods: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case–control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations. Results: Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24–4.61; Ptrend < 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P < 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P = 0.25, 0.71, and 0.61, respectively). Conclusions: Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. Cancer Epidemiol Biomarkers Prev; 26(6); 945–52. ©2017 AACR.

Background: Evidence evaluating the association between type of coffee intake (caffeinated, decaffeinated) and risk of pancreatic cancer is limited. Methods: In the US NIH-AARP Diet and Health Study, we used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for coffee intake and risk of pancreatic cancer among 457 366 US adults. Results: Over 4 155 256 person-years of follow-up, 1541 incident first primary pancreatic cancers occurred. Following detailed adjustment for tobacco smoking history, risk estimates for coffee drinking were not statistically significant; compared with never drinkers of coffee, the hazard ratios (95% CI) were 1.05 (0.85–1.30), 1.06 (0.86–1.31), 1.03 (0.85–1.25), 1.00 (0.79–1.25), and 1.24 (0.93–1.65) for

Background: Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study. Methods: Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use. Results: Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuated after adjusting for smoking (HR: 1.27, 1.14-1.42). Similar findings were observed for each different histological type of lung cancer, and for participants drinking predominantly caffeinated or decaffeinated coffee. Little evidence for an association was observed in our stratified analyses, either within never smokers or in most categories of tobacco use. Conclusions: Coffee drinking was positively associated with lung cancer in our study, although the association was substantially attenuated after adjustment for tobacco smoking. As our adjustment for lifetime tobacco use was imperfect, it is likely that the remaining association is due to residual confounding by smoking, although other explanations are possible.

Background: Coffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms. Objectives: Our aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer. Design: In a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography–tandem mass spectrometry and gas chromatography–mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer. Results: After Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18–0.61; P 0.40) included trigonelline (N′-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer. Conclusions: Serum metabolites can distinguish coffee drinkers from nondrinkers; some caffeine-related metabolites were inversely associated with colorectal cancer and should be studied further to clarify the role of coffee in the cause of colorectal cancer. The Prostate, Lung, Colorectal, and Ovarian trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00002540","term_id":"NCT00002540"}}NCT00002540.

Metabolomic markers associated with incident central adiposity gain were investigated in young adults. In a 9-mo prospective study of university freshmen (n = 264). Blood samples and anthropometry measurements were collected in the first 3 d on campus and at the end of the year. Plasma from individuals was pooled by phenotype [incident central adiposity, stable adiposity, baseline hemoglobin A1c (HbA1c) > 5.05%, HbA1c < 4.92%] and assayed using GC-MS, chromatograms were analyzed using MetaboliteDetector software, and normalized metabolite levels were compared using Welch's t test. Assays were repeated using freshly prepared pools, and statistically significant metabolites were quantified in a targeted GC-MS approach. Isotope tracer studies were performed to determine if the potential marker was an endogenous human metabolite in men and in whole blood. Participants with incident central adiposity gain had statistically significantly higher blood erythritol [P < 0.001, false discovery rate (FDR) = 0.0435], and the targeted assay revealed 15-fold [95% confidence interval (CI): 13.27, 16.25] higher blood erythritol compared with participants with stable adiposity. Participants with baseline HbA1c > 5.05% had 21-fold (95% CI: 19.84, 21.41) higher blood erythritol compared with participants with lower HbA1c (P < 0.001, FDR = 0.00016). Erythritol was shown to be synthesized endogenously from glucose via the pentose-phosphate pathway (PPP) in stable isotope-assisted ex vivo blood incubation experiments and through in vivo conversion of erythritol to erythronate in stable isotope-assisted dried blood spot experiments. Therefore, endogenous production of erythritol from glucose may contribute to the association between erythritol and obesity observed in young adults.

We investigated predictors of weight gain in college freshmen.A longitudinal cohort study followed a representative sample of freshmen (N = 264) from 8/2011 to 6/2012.Repeated measurements of anthropometry, dual-energy X-ray absorptiometry (DXA), physical activity, and diet were collected. We investigated predictors of 9-month weight gain using regression models.172 participants completed follow-up: 75% gained0.5 kg. Mean weight change was +2.3 kg (SD 3.2) and +2.0 kg (SD 3.2) and mean adiposity change was +1.3% (SD 1.6) and +0.7% (SD 2.2) in men and women, respectively. In participants gaining0.5 kg, weight increased 5.6% and body fat increased 1.6%. Anthropometric change in men occurred in the first semester, while women increased in both semesters. Leaner DXA-defined body composition at baseline was consistently associated with greater weight gain (p-values 0.029-0.049).Freshman weight gain is common and reflects increased adiposity. Leaner body composition at the beginning of college predicted greater weight gain in men and women during the first year of college.

Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet, the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one’s diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study (AACES), the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR=1.10, 95% CI=1.03–1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1=1.72; 95% CI=1.18–2.51). We also observed effect modification by age (p

Background Cigarette smoking generates reactive oxidant species and contributes to systemic oxidative stress, which plays a role in the pathophysiology of chronic diseases. Nutrients with antioxidant properties, including vitamin E and selenium, are proposed to reduce systemic oxidative burden and thus to mitigate the negative health effects of reactive oxidant species. Objective Our objective was to determine whether long-term supplementation with vitamin E and/or selenium reduces oxidative stress in smokers, as measured by urine 8-iso-prostaglandin F 2-alpha (8-iso-PGF 2α ). Design We measured urine 8-iso-PGF 2α with competitive enzyme linked immunoassay (ELISA) in 312 male current smokers after 36 months of intervention in a randomized placebo-controlled trial of vitamin E (400 IU/d all rac -α-tocopheryl acetate) and/or selenium (200 µg/d L -selenomethionine). We used linear regression to estimate the effect of intervention on urine 8-iso-PGF 2α , with adjustments for age and race. Results Compared to placebo, vitamin E alone lowered urine 8-iso-PGF 2α by 21% ( p =0.02); there was no effect of combined vitamin E and selenium (intervention arm lower by 9%; p =0.37) or selenium alone (intervention arm higher by 8%; p =0.52). Conclusions Long-term vitamin E supplementation decreases urine 8-iso-PGF 2α among male cigarette smokers, but we observed little to no evidence for an effect of selenium supplementation, alone or combined with vitamin E.

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.

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 (

Background The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. Methods The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. Results Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25–75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25–75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25–75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. Conclusions Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25–75, a marker of airflow. Trial registration Clinicaltrials.gov identifier: NCT00241865. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0195-5) contains supplementary material, which is available to authorized users.

Background Time to first cigarette (TTFC) after waking is an indicator of nicotine dependence. The association between TTFC and chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, has not yet been reported. Methods We investigated the cross-sectional association between TTFC and prevalent COPD among 6,108 current smokers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. COPD was defined as a self-reported diagnosis of emphysema, chronic bronchitis, or both. Current smokers in PLCO reported TTFC, the amount of time they typically waited before smoking their first cigarette of the day after waking, in four categories: ≤5, 6-30, 31-60, or >60 minutes. We used logistic regression models to investigate the association between TTFC and prevalent COPD with adjustments for age, gender, race, education, and smoking (cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation), and prior lung cancer diagnosis. Results COPD was reported by 19% of these 6,108 smokers. Individuals with the shortest TTFC had the greatest risk of COPD; compared to those with the longest TTFC (>60 minutes) the adjusted odds ratios (OR) and 95% confidence intervals (CI) for COPD were 1.48 (95% CI, 1.15-1.91), 1.64 (95% CI, 1.29-2.08), 2.18 (95% CI, 1.65-2.87) for those with TTFC 31-60 minutes, 6-30 minutes, and ≤5 minutes, respectively (P-trend 60 minutes, the adjusted OR (95% CI) was 2.29 (1.69-3.12) for emphysema and 2.99 (1.95-4.59) for chronic bronchitis. Conclusions Current smokers with shorter TTFC have increased risk of COPD compared to those with longer TTFC, even after comprehensive adjustment for established smoking covariates. Future epidemiologic studies, including prospective designs, should incorporate TTFC to better assess disease risk and evaluate the potential utility of TTFC as a COPD screening tool for smokers in the clinical setting.

Background: Metabolomics is an emerging field with the potential to advance nutritional epidemiology; however, it has not yet been applied to large cohort studies. Objectives: Our first aim was to identify metabolites that are biomarkers of usual dietary intake. Second, among serum metabolites correlated with diet, we evaluated metabolite reproducibility and required sample sizes to determine the potential for metabolomics in epidemiologic studies. Design: Baseline serum from 502 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was analyzed by using ultra-high-performance liquid-phase chromatography with tandem mass spectrometry and gas chromatography‐mass spectrometry. Usual intakes of 36 dietary groups were estimated by using a food-frequency questionnaire. Dietary biomarkers were identified by using partial Pearson’s correlations with Bonferroni correction for multiple comparisons. Intraclass correlation coefficients (ICCs) between samples collected 1 y apart in a subset of 30 individuals were calculated to evaluate intraindividual metabolite variability. Results: We detected 412 known metabolites. Citrus, green vegetables, red meat, shellfish, fish, peanuts, rice, butter, coffee, beer, liquor, total alcohol, and multivitamins were each correlated with at least one metabolite (P , 1.093 3 10 26 ; r = 2 0.312 to 0.398); in total, 39 dietary biomarkers were identified. Some correlations (citrus intake with stachydrine) replicated previous studies; others, such as peanuts and tryptophan betaine, were novel findings. Other strong associations included coffee (with trigonelline-N-methylnicotinate and quinate) and alcohol (with ethyl glucuronide). Intraindividual variability in metabolite levels (1-y ICCs) ranged from 0.27 to 0.89.Large, but attainable, sample sizes are required to detect associations between metabolites and disease in epidemiologic studies, further emphasizing the usefulness of metabolomics in nutritional epidemiology. Conclusions: We identified dietary biomarkers by using metabolomics in an epidemiologic data set. Given the strength of the associations observed, we expect that some of these metabolites will be validated in future studie sa nd later used as biomarkers in large cohorts to study diet-disease associations. The PLCO trial was registered at clinicaltrials.gov as NCT00002540. Am J Clin Nutr 2014;100:208‐17.