Dietaryindex: A User-Friendly and Versatile R Package for Standardizing Dietary Pattern Analysis in Epidemiological and Clinical Studies.

Background: Few standardized and open-source tools exist for calculating dietary pattern indexes from dietary intake data in epidemiological and clinical studies. Miscalculations of dietary indexes, with suspected erroneous findings, are occasionally noted in the literature. Objective: The primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes. Methods: Dietaryindex utilizes a two-step process: an initial calculation of serving size for each food and nutrient category, followed by the calculation of individual dietary indexes. It includes generic functions that accept any preprocessed serving sizes of food groups and nutrients, with the standard serving sizes defined according to the methodologies used in well-known prospective cohort studies. For ease of use, dietaryindex also offers one-step functions that directly reference common datasets and tools, including the National Health and Nutrition Examination Survey (NHANES) and Block Food Frequency Questionnaire, eliminating the need for data preprocessing. At least two independent researchers validated the serving size definitions and scoring algorithms of dietaryindex. Results: Dietaryindex can calculate multiple dietary indexes of high interest in research, including Healthy Eating Index (HEI) - 2020, Alternative Healthy Eating Index 2010, Dietary Approaches to Stop Hypertension Index, Alternate Mediterranean Diet Score, Dietary Inflammatory Index, American Cancer Society 2020 dietary index, and Planetary Health Diet Index from the EAT-Lancet Commission. In our validation process, dietaryindex demonstrated full accuracy (100%) in all generic functions with two-decimal rounding precision in comparison to hand-calculated results. Similarly, using NHANES 2017-2018 data and ASA24 and DHQ3 example data, the HEI2015 outputs from dietaryindex aligned (99.95%-100%) with results using the SAS codes from the National Cancer Institute. Conclusions: Dietaryindex is a user-friendly, versatile, and validated informatics tool for standardized dietary index calculations. We have open-sourced all the validation files and codes with detailed tutorials on GitHub (https://github.com/jamesjiadazhan/dietaryindex).

Change in Diet Quality and Meal Sources during the COVID-19 Pandemic in a Diverse Subset of Men and Women in the Cancer Prevention Study-3.

The COVID-19 pandemic resulted in restrictive measures that caused disruptions in behaviors that may have long-term consequences on diet, health, and chronic disease risk. The aim of this study was to assess longitudinal changes in diet quality from before to during the pandemic among 2335 adult participants (816 males and 1519 females; aged 36-78) of the Cancer Prevention Study-3 cohort. We compared dietary screeners conducted in 2018 and 2020 and calculated a diet quality score, which assigned higher points for recommended foods. Overall diet quality slightly improved among all participants from before to during the pandemic, particularly among males (+0.45 points, p < 0.001), White participants (+0.24 points, p < 0.001), and participants reporting weight loss (+0.66 points, p < 0.001 for 2.25 -< 4.5 kg loss; +1.04 points, p < 0.001 for ≥4.5 kg loss); change in diet quality did not differ by other sociodemographic factors. Reported consumption of most food groups decreased, especially whole grains (-0.17 servings/day, p < 0.001) and vegetables (-0.21 servings/day, p < 0.001), primarily among females, Black participants, and participants who gained ≥2.25 kg. The frequency of meals from outside the home decreased, especially in full-service restaurants (-0.47 times/week, p < 0.001) and for ready-to-eat meals (-0.37 times/week, p < 0.001). Declines in whole grain and vegetable consumption raise concerns for weight gain in these populations and increased risk of poor metabolic health and chronic disease.

Consistent and changing consumption of fast-food and full-service meals and 3-year weight change in a large population cohort study.

BACKGROUND: An average American consumes 3 meals weekly from fast-food or full-service restaurants, which contain more calories, fat, sodium, and cholesterol than meals prepared at home. OBJECTIVES: This study examined whether consistent and changing fast-food or full-service consumption was associated with weight change over a 3-y period. METHODS: Among 98,589 US adults from the American Cancer Society's Cancer Prevention Study-3, self-reported weight and fast-food and full-service consumption from 2015 and 2018 were examined using a multivariable-adjusted linear regression analysis to assess the association of consistent and changing consumption on 3-y weight change. RESULTS: Individuals who made no changes to their fast-food or full-service intake over the study period gained weight regardless of consumption frequency, although low consumers gained less weight than high consumers (low fast-food: ß = -1.08; 95% CI: -1.22, -0.93; low full-service: ß = -0.35; 95% CI: -0.50, -0.21; P < 0.001). Decreased fast-food intake during the study period (e.g., from high [>1 meal/wk] to low [≤0.5 meal/wk], high to medium [>0.5 to ≤1 meal/wk], or medium to low) and decreased full-service intake from high (≥1 meal/wk) to low (<1 meal/mo) were significantly associated with weight loss (high-low: ß = -2.77; 95% CI: -3.23, -2.31; high-medium: ß = -1.53; 95% CI: -1.72, -1.33; medium-low: ß = -0.85; 95% CI: -1.06, -0.63; high-low full-service: ß = -0.92; 95% CI: -1.36, -0.49; P < 0.001). Decreased consumption of both fast-food and full-service restaurant meals was associated with greater weight loss than decreasing fast-food alone (both: ß = -1.65; 95% CI: -1.82, -1.37; fast-food only: ß = -0.95; 95% CI: -1.12, -0.79; P < 0.001). CONCLUSIONS: Decreased consumption of fast-food and full-service meals over 3 y, particularly among high consumers at baseline, was associated with weight loss and may be an effective approach to weight loss. Moreover, decreasing both fast-food and full-service meal consumption was associated with a greater weight loss than decreasing only fast-food meal consumption.

Sugar- and Artificially-Sweetened Beverages and Cancer Mortality in a Large U.S. Prospective Cohort.

BACKGROUND: Sugar-sweetened beverage (SSB) consumption may be associated with cancer mortality independent of, or indirectly through, established influences on increased body adiposity. METHODS: We examined the associations of SSBs and artificially-sweetened beverages (ASB) with mortality from all-cancers combined, obesity-related cancers combined, and 20 cancer types, among men and women in the Cancer Prevention Study-II (CPS-II) prospective cohort. In 1982, 934,777 cancer-free participants provided information on usual SSB and ASB consumption. Deaths were identified through 2016. Multivariable Cox proportional hazards regression models examined associations of beverage types with cancer mortality, without and with BMI adjustment. RESULTS: During follow-up, 135,093 CPS-II participants died from cancer. Consumption of ≥2 SSB drinks/day vs. never was not associated with all-cancer mortality, but was associated with increased risk of obesity-related cancers [HR, 1.05; 95% confidence intervals (CI), 1.01-1.08; Ptrend = 0.057], which became null after adjustment for BMI. SSBs were associated with increased mortality from colorectal (HR, 1.09; 95% CI, 1.02-1.17; Ptrend = 0.011), and kidney (HR, 1.17; 95% CI, 1.03-1.34; Ptrend = 0.056) cancers, which remained after BMI adjustment. A positive association of ASB consumption with obesity-related cancers (HR, 1.05; 95% CI, 1.01-1.08; Ptrend = 0.001) was null after controlling for BMI; however, an increased risk of pancreatic cancer was robust to BMI adjustment (HR, 1.11; 95% CI, 1.02-1.20; Ptrend < 0.008). CONCLUSIONS: SSB consumption was associated with higher mortality from certain cancers, partially mediated through obesity. Associations of ASB consumption and increased pancreatic cancer risk merit further study. IMPACT: Future research should consider the role of BMI in studies of sweetened beverages and cancer risk. These results should inform policy regarding sweetened beverage consumption.

Self-Reported Dietary Supplement Use Is Reproducible and Relatively Valid in the Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Dietary supplement use is common, particularly among cancer survivors and those at increased risk for cancer. OBJECTIVE: The objectives of this study were to assess 1-year test-retest reproducibility of dietary supplement use reported via food frequency questionnaire (FFQ-1 vs FFQ-2) and relative validity in comparison to repeated 24-hour dietary recalls (FFQ-2 vs DRs). DESIGN: This ancillary study was conducted within a large prospective cohort, the American Cancer Society's Cancer Prevention Study-3. PARTICIPANTS/SETTING: Between 2015 and 2016, 684 participants in the United States (64% women; 62% non-Hispanic White, 23% non-Hispanic Black, and 15% Hispanic) completed two FFQs and up to six unannounced telephone interviewer-administered DRs over 1 year as part of the Cancer Prevention Study-3 Diet Assessment Substudy. PRIMARY OUTCOME MEASURES: FFQs queried current multivitamin-mineral supplement (≥10 components) use, frequency and dose (range) for seven supplements taken individually or as part of a complex (individual/complex) including calcium, vitamins D, C, and E, folic acid, fish oil, and glucosamine. DRs allowed exact reporting of supplement frequency and dose. STATISTICAL ANALYSES: Weighted κ statistics were used to evaluate reproducibility between FFQ-1 and FFQ-2 and Spearman correlation coefficients assessed agreement between supplemental nutrient amounts assessed by FFQ-2 and the average of DRs. RESULTS: Just more than half of the participants reported taking multivitamin-mineral supplements on the baseline FFQ. Kappa statistics for the comparison of categorical responses between FFQ-1 and FFQ-2 were 0.67 for multivitamin-mineral supplements. Kappas for individual/complex supplements ranged from 0.47 for folic acid to 0.74 for vitamin D, with a mean of 0.64. Results were similar between men and women. Spearman correlation coefficients comparing FFQ-2 with the average of DRs (validity) for nutrient intakes from all sources ranged from 0.65 (fish oil for women) to 0.77 (vitamin D for men and calcium for women); results were similar among men and women. CONCLUSIONS: These findings suggest the FFQ used in Cancer Prevention Study-3 has good reproducibility over 1 year and yields estimates comparable to a more detailed assessment for commonly consumed dietary supplements.

Association of Emulsifier and Highly Processed Food Intake with Circulating Markers of Intestinal Permeability and Inflammation in the Cancer Prevention Study-3 Diet Assessment Sub-Study.

Compelling animal studies report increased intestinal permeability, inflammation, and colorectal carcinogenesis with exposure to certain emulsifiers commonly added to processed foods, but human data are lacking. Highly processed food consumption is also associated with obesity and higher risk of chronic diseases. We cross-sectionally examined the association of emulsifier and highly processed food consumption estimated from six 24-h dietary recalls among 588 U.S. men and women over one year, with biomarkers of intestinal permeability and inflammation measured from two fasting blood samples collected six months apart. In multivariable-adjusted generalized linear models, greater emulsifier intake (g/d) was not associated with antibodies to flagellin (P-trend = 0.88), lipopolysaccharide (LPS) (P-trend = 0.56), or the combined total thereof (P-trend = 0.65) but was positively associated with an inflammatory biomarker, glycoprotein acetyls (GlycA) (P-trend = 0.02). Highly processed food intake (% kcal/d) was associated with higher anti-LPS antibodies (P-trend = 0.001) and total anti-flagellin and anti-LPS antibodies (P-trend = 0.005) but not with other biomarkers, whereas processed food intake expressed as % g/d was associated with higher GlycA (P-trend = 0.02). Our findings suggest that, broadly, highly processed food consumption may be associated with intestinal permeability biomarkers, and both emulsifier and highly processed food intakes may be associated with inflammation. Additional studies are warranted to further evaluate these relationships.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1957947.

Prospective changes in physical activity, sedentary time and sleep during the COVID-19 pandemic in a US-based cohort study.

OBJECTIVES: Assess differences in movement behaviours within the 24-hour cycle, including light intensity physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time and sleep, before and during the COVID-19 pandemic and assess these differences stratified by several relevant factors in a subcohort of the Cancer Prevention Study-3. DESIGN AND SETTING: US-based longitudinal cohort study (2018-August 2020). PARTICIPANTS: N=1992 participants, of which 1304 (65.5%) are women, and 1512 (75.9%) are non-Latino white, with a mean age 57.0 (9.8) years. MEASURES: Age, sex, race/ethnicity, education; self-reported LPA, MVPA, sedentary time and sleep duration collected before and during the pandemic; pandemic-related changes in work, childcare and living arrangement; COVID-19 health history. RESULTS: Compared to 2018, participants spent an additional 104 min/day sedentary, 61 fewer min/day in LPA and 43 fewer min/day in MVPA during the pandemic. Time spent sleeping was similar at the two time points. Differences in movement behaviours were more pronounced among men, those with a higher level of education, and those who were more active before the pandemic. CONCLUSIONS: From 2018 to Summer 2020, during the COVID-19 pandemic, US adults have made significant shifts in daily time spent in LPA, MVPA and sedentary. There is an urgent need to promote more physical activity and less sedentary time during this public health crisis to avoid sustaining these patterns long-term.

Identification and Reproducibility of Urinary Metabolomic Biomarkers of Habitual Food Intake in a Cross-Sectional Analysis of the Cancer Prevention Study-3 Diet Assessment Sub-Study.

Previous cross-sectional metabolomics studies have identified many potential dietary biomarkers, mostly in blood. Few studies examined urine samples although urine is preferred for dietary biomarker discovery. Furthermore, little is known regarding the reproducibility of urinary metabolomic biomarkers over time. We aimed to identify urinary metabolomic biomarkers of diet and assess their reproducibility over time. We conducted a metabolomics analysis among 648 racially/ethnically diverse men and women in the Diet Assessment Sub-study of the Cancer Prevention Study-3 cohort to examine the correlation between >100 food groups/items [101 by a food frequency questionnaire (FFQ), and 105 by repeated 24 h diet recalls (24HRs)] and 1391 metabolites measured in 24 h urine sample replicates, six months apart. Diet-metabolite associations were examined by Pearson's partial correlation analysis. Biomarkers were evaluated for prediction accuracy assessed using area under the curve (AUC) calculated from the receiver operating characteristic curve and for reproducibility assessed using intraclass correlation coefficients (ICCs). A total of 1708 diet-metabolite associations were identified after Bonferroni correction for multiple comparisons and restricting correlation coefficients to >0.2 or <-0.2 (1570 associations using the FFQ and 933 using 24HRs), 513 unique metabolites correlated with 79 food groups/items. The median ICCs of the 513 putative biomarkers was 0.53 (interquartile range 0.42-0.62). In this study, with comprehensive dietary data and repeated 24 h urinary metabolic profiles, we identified a large number of diet-metabolite correlations and replicated many found in previous studies. Our findings revealed the promise of urine samples for dietary biomarker discovery in a large cohort study and provide important information on biomarker reproducibility, which could facilitate their utilization in future clinical and epidemiological studies.

Pre-Diagnostic Circulating Metabolites and Colorectal Cancer Risk in the Cancer Prevention Study-II Nutrition Cohort.

Untargeted metabolomic studies have identified potential biomarkers of colorectal cancer risk, but evidence is still limited and broadly inconsistent. Among 39,239 Cancer Prevention Study II Nutrition cohort participants who provided a blood sample between 1998-2001, 517 newly diagnosed colorectal cancers were identified through 30 June 2015. In this nested case-control study, controls were matched 1:1 to cases on age, sex, race and date of blood draw. Mass spectroscopy-based metabolomic analyses of pre-diagnostic plasma identified 886 named metabolites, after quality control exclusions. Conditional logistic regression models estimated multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) for 1 standard deviation (SD) increase in each metabolite with risk of colorectal cancer. Six metabolites were associated with colorectal cancer risk at a false discovery rate < 0.20. These metabolites were of several classes, including cofactors and vitamins, nucleotides, xenobiotics, lipids and amino acids. Five metabolites (guanidinoacetate, 2'-O-methylcytidine, vanillylmandelate, bilirubin (E,E) and N-palmitoylglycine) were positively associated (OR per 1 SD = 1.29 to 1.32), and one (3-methylxanthine) was inversely associated with CRC risk (OR = 0.79, 95% CI, 0.69-0.89). We did not replicate findings from two earlier prospective studies of 250 cases each after adjusting for multiple comparisons. Large pooled prospective analyses are warranted to confirm or refute these findings and to discover and replicate metabolites associated with colorectal cancer risk.

The Cancer Prevention Study-3 FFQ Is a Reliable and Valid Measure of Nutrient Intakes among Racial/Ethnic Subgroups, Compared with 24-Hour Recalls and Biomarkers.

BACKGROUND: Valid assessment of dietary intake in diverse populations is important for studies of chronic disease risk in the United States. OBJECTIVES: We evaluated the reproducibility and validity of a food frequency questionnaire (FFQ) modified for the American Cancer Society's Cancer Prevention Study-3 (CPS-3) prospective cohort, among a racially/ethnically diverse subgroup. METHODS: The Diet Assessment Substudy included 677 CPS-3 participants (64% women; 61% non-Hispanic white, 24% non-Hispanic black, 15% Hispanic), aged 31-70 y, who completed 2 FFQs 1 y apart (FFQ1, FFQ2), 4-6 telephone-administered 24-h dietary recalls (24HRs), and 2 fasting blood samples and 24-h urine collections ∼6 mo apart in the interim. Spearman rank correlation coefficients (ρ) were used to evaluate FFQ reproducibility and validity compared with 24HRs for 67 nutrient exposures. For 18 of these nutrients, we used the method of triads to calculate validity coefficients (VCs, ρ) from pairwise correlations of FFQ2, 24HRs, and biomarkers. Analyses were stratified by sex, race/ethnicity, education, and BMI. RESULTS: Mean (range) FFQ reproducibility correlations were ρ = 0.65 (0.50-0.91) for men and ρ = 0.63 (0.37-0.89) for women; mean (range) energy-adjusted, deattenuated correlations of FFQ2 with 24HRs were ρ = 0.60 (0.33-0.84) for men and ρ = 0.55 (0.21-0.79) for women. FFQ2 VCs (ρ) among men ranged from 0.42 for ß-cryptoxanthin to 0.91 for omega-3 (n-3) fatty acids and, among women, from 0.41 for sodium to 0.79 for total vitamin D. Mean FFQ reproducibility and validity were highest among whites (ρ = 0.68, ρ = 0.58, respectively) and slightly lower among blacks (ρ = 0.57, ρ = 0.49, respectively) and Hispanics (ρ = 0.59, 0.55, respectively). FFQ reproducibility and validity were slightly lower among those with less than a 4-y college degree, and those with a BMI ≥30 kg/m2. CONCLUSIONS: Reproducibility and validity of the CPS-3 FFQ were comparable with similar studies for most nutrients, among all subgroups. These findings support future dietary analyses in the contemporary CPS-3 cohort and other similar cohorts.

Identification and Reproducibility of Plasma Metabolomic Biomarkers of Habitual Food Intake in a US Diet Validation Study.

Previous metabolomic studies have identified putative blood biomarkers of dietary intake. These biomarkers need to be replicated in other populations and tested for reproducibility over time for the potential use in future epidemiological studies. We conducted a metabolomics analysis among 671 racially/ethnically diverse men and women included in a diet validation study to examine the correlation between >100 food groups/items (101 by a food frequency questionnaire (FFQ), 105 by 24-h diet recalls (24HRs)) with 1141 metabolites measured in fasting plasma sample replicates, six months apart. Diet-metabolite associations were examined by Pearson's partial correlation analysis. Biomarker reproducibility was assessed using intraclass correlation coefficients (ICCs). A total of 677 diet-metabolite associations were identified after Bonferroni adjustment for multiple comparisons and restricting absolute correlation coefficients to greater than 0.2 (601 associations using the FFQ and 395 using 24HRs). The median ICCs of the 238 putative biomarkers was 0.56 (interquartile range 0.46-0.68). In this study, with repeated FFQs, 24HRs and plasma metabolic profiles, we identified several potentially novel food biomarkers and replicated others found in our previous study. Our findings contribute to the growing literature on food-based biomarkers and provide important information on biomarker reproducibility which could facilitate their utilization in future nutritional epidemiological studies.

Coffee Consumption and Invasive Breast Cancer Incidence among Postmenopausal Women in the Cancer Prevention Study-II Nutrition Cohort.

BACKGROUND: There is limited evidence of a potential inverse association between coffee, particularly caffeinated coffee, consumption and postmenopausal breast cancer risk, and few studies have examined this association by tumor hormone receptor status. To provide further evidence, we examined total, caffeinated, and decaffeinated coffee consumption in relation to postmenopausal invasive breast cancer incidence overall, and by tumor estrogen receptor (ER) and/or progesterone receptor (PR) subtype. METHODS: Among 57,075 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort who were cancer free and reported coffee intake in 1999, we identified 2,980 women diagnosed with invasive breast cancer during follow-up through June 2015. Multivariable-adjusted Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Neither total, caffeinated, nor decaffeinated coffee consumption was associated with invasive breast cancer risk; HRs (95% CIs) comparing consumption of ≥2 cups per day with <1 cup per month were 0.99 (0.89-1.11), 0.96 (0.87-1.06), and 1.06 (0.95-1.19), respectively. Similarly, coffee consumption was not associated with risk of hormone receptor-positive (ER+ or PR+) or hormone receptor-negative (ER- and PR-) breast tumors. CONCLUSIONS: These findings do not support an association between coffee consumption and invasive breast cancer risk among postmenopausal women. IMPACT: This large prospective study contributes to the limited evidence on coffee consumption and breast cancer risk, finding no association overall or by tumor receptor subtype.

The American Cancer Society Cancer Prevention Study-3 FFQ Has Reasonable Validity and Reproducibility for Food Groups and a Diet Quality Score.

BACKGROUND: FFQs are commonly used to assess dietary intake and it is important to evaluate their performance in the target population. OBJECTIVE: We evaluated the reproducibility and relative validity of the Cancer Prevention Study-3 (CPS-3) FFQ in estimating usual intake of 63 food groups and diet quality in accordance with the American Cancer Society dietary guidelines for cancer prevention. METHODS: A subset of participants from the CPS-3 (433 women, 244 men), 31-70 y of age, were included in a cross-sectional diet assessment substudy (2015-2016). Reproducibility was assessed by comparing estimates from repeat FFQs, approximately 1 y apart, using Spearman correlation coefficient (rs) and Pearson correlation coefficient (rp) correlations for food groups and diet quality, respectively. Validity was assessed similarly by comparing FFQ estimates with estimates from ≤6 interviewer-administered 24-h dietary recall (24HR). Analyses were stratified by sex and race/ethnicity. RESULTS: Reproducibility correlations for repeated FFQs were > 0.50 for 83-97% of food groups analyzed across strata of sex and race. Although participants tended to overreport plant foods (e.g., fruits and legumes) and underreport refined grains and sugar-sweetened beverages, the median energy-adjusted, deattenuated Spearman correlations comparing the second FFQ to the 24HR were 0.50 and 0.52 among men and women (range: 0.05-0.82), respectively, suggesting that ranking was preserved for most food groups. Validity was highest for coffee, alcohol, and total dairy, and lowest for pasta and regular-fat yogurt. Median validity across food groups varied by race/ethnicity and was highest among whites (rs = 0.54) followed by Hispanics (rs = 0.49) and African Americans (rs = 0.45). The diet quality score had good validity in all subgroups examined, but was higher among men (rp = 0.69) than women (rp = 0.61), and lower among whites (rp = 0.62) than Hispanics (rp = 0.64) or African Americans (rp = 0.73). CONCLUSIONS: This study indicates good reproducibility and validity of the CPS-3 FFQ for most major food groups and the diet quality score in all sex and race/ethnicity groups examined.

Metabolomic markers of healthy dietary patterns in US postmenopausal women.

BACKGROUND: Healthy diet patterns are associated with lower risk of cancer and other chronic diseases. Metabolomics has the potential to expand dietary biomarker development to include dietary patterns, which may provide a complement or alternative to self-reported diet. OBJECTIVE: This study examined the correlation of serum untargeted metabolomic markers with 4 diet pattern scores-the alternate Mediterranean diet score (aMED), alternate Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Healthy Eating Index (HEI)-2015-and used multivariate methods to identify discriminatory metabolites for each pattern. METHODS: Among 1367 US postmenopausal women with serum metabolomic data in the Cancer Prevention Study-II Nutrition Cohort, we conducted partial correlation analysis, adjusted for demographic and lifestyle variables, to examine cross-sectional correlations between serum metabolomic markers and healthy diet pattern scores. In a randomly selected "training" set (50%), we conducted orthogonal partial least-squares discriminant analysis to identify metabolites that discriminated the top from bottom diet score quintiles. Combinations of metabolites with a variable importance in projection (VIP) score ≥2.5 were tested for predictability in the "testing" set based on the use of receiver operating characteristic curves. RESULTS: Out of 1186 metabolites, 32 unique metabolites were considered discriminatory based on a VIP score ≥2.5 in the training dataset with some overlap across scores (aMED = 16; AHEI = 17; DASH = 13; HEI = 12). Spearman partial correlation analyses, applying a cut-point (|r| ≥ 0.15) and Bonferroni correction (P < 1.05 × 10-5), identified similar key metabolites. The top 5 metabolites for each pattern mostly distinguished high compared with low scores; 4 of the 5 (fish-derived) metabolites were the same for aMED and AHEI, 2 of which were identified for HEI; 4 DASH metabolites were unique. CONCLUSIONS: Metabolomic methods that used a split-sample approach identified potential biomarkers for 4 healthy diet patterns. Similar metabolites across scores reflect fish consumption in healthy dietary patterns. These findings should be replicated in independent populations.

Dietary Acrylamide Is Not Associated with Renal Cell Cancer Risk in the CPS-II Nutrition Cohort.

BACKGROUND: Acrylamide, an industrial chemical and probable human carcinogen, can be formed in primarily carbohydrate-containing foods during high-heat cooking or processing. Most epidemiologic studies show no associations of dietary acrylamide intake with most cancer outcomes, but limited prospective evidence suggests a positive association with renal cell carcinoma (RCC). METHODS: In 1999, 102,154 men and women from the Cancer Prevention Study-II Nutrition Cohort completed a questionnaire on diet, lifestyle, and cancer risk factors and were followed through June 30, 2013. Cox proportional hazards regression was used to estimate the HR and 95% confidence interval (CI) for the association between estimated dietary acrylamide intake and risk of RCC. RESULTS: After 1,137,441 person-years of follow-up, 412 cases of invasive RCC occurred. In multivariable-adjusted models, there was no association between acrylamide intake and risk of RCC (HR = 1.09; 95% CI, 0.82-1.43) for the highest versus lowest quartile of intake. Associations were not modified by sex or smoking history. CONCLUSIONS: We found no associations between dietary acrylamide exposure and risk of invasive RCC. IMPACT: The findings from this large, prospective analysis do not support a positive association between higher dietary acrylamide intake and RCC risk.