Publications by authors named "Marjorie L McCullough"

212 Publications

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

J Acad Nutr Diet 2021 Aug 12. Epub 2021 Aug 12.

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.
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http://dx.doi.org/10.1016/j.jand.2021.07.006DOI Listing
August 2021

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.

Nutr Cancer 2021 Aug 6:1-11. Epub 2021 Aug 6.

Department of Population Science, American Cancer Society, Atlanta, GA, USA.

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 (-trend = 0.88), lipopolysaccharide (LPS) (-trend = 0.56), or the combined total thereof (-trend = 0.65) but was positively associated with an inflammatory biomarker, glycoprotein acetyls (GlycA) (-trend = 0.02). Highly processed food intake (% kcal/d) was associated with higher anti-LPS antibodies (-trend = 0.001) and total anti-flagellin and anti-LPS antibodies (-trend = 0.005) but not with other biomarkers, whereas processed food intake expressed as % g/d was associated with higher GlycA (-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.
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http://dx.doi.org/10.1080/01635581.2021.1957947DOI Listing
August 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 08;114(2):450-461

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326053PMC
August 2021

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.

Metabolites 2021 Apr 17;11(4). Epub 2021 Apr 17.

Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA.

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.
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http://dx.doi.org/10.3390/metabo11040248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072637PMC
April 2021

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

Metabolites 2021 Mar 9;11(3). Epub 2021 Mar 9.

Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA.

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 -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.
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http://dx.doi.org/10.3390/metabo11030156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000483PMC
March 2021

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.

J Nutr 2021 03;151(3):636-648

Department of Population Science, American Cancer Society, Atlanta, GA, USA.

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 β-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.
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http://dx.doi.org/10.1093/jn/nxaa358DOI Listing
March 2021

Response to letter to the editor: Caffeinated and decaffeinated coffee intake and colorectal cancer: A risk assessment.

Cancer Epidemiol 2020 12 22;69:101843. Epub 2020 Oct 22.

Department of Population Science, American Cancer Society, Atlanta, GA, United States.

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http://dx.doi.org/10.1016/j.canep.2020.101843DOI Listing
December 2020

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

Metabolites 2020 Sep 26;10(10). Epub 2020 Sep 26.

Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA.

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.
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http://dx.doi.org/10.3390/metabo10100382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600452PMC
September 2020

Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2021 02 28;22(1-2):133-143. Epub 2020 Sep 28.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Objective: To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women's Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18-2.69, trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07-2.73, trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.
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http://dx.doi.org/10.1080/21678421.2020.1822411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004541PMC
February 2021

Inflammation Modulation by Vitamin D and Calcium in the Morphologically Normal Colorectal Mucosa of Patients with Colorectal Adenoma in a Clinical Trial.

Cancer Prev Res (Phila) 2021 01 11;14(1):65-76. Epub 2020 Sep 11.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group ( = 0.001), 46% in the calcium group ( = 0.002), and 34% in the calcium + vitamin D group ( = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoform DBP2 ( rs4588*A), the COX-2/15-HPDG ratio decreased 70% ( = 0.0006), 75% ( = 0.0002), and 60% ( = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorably modulate the balance of expression of COX-2 and 15-HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform). PREVENTION RELEVANCE: Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947029PMC
January 2021

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

Cancer Epidemiol Biomarkers Prev 2020 11 14;29(11):2383-2386. Epub 2020 Aug 14.

Department of Population Science, American Cancer Society, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1051DOI Listing
November 2020

Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.

Cancer Epidemiol 2020 08 9;67:101730. Epub 2020 Jun 9.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, United States.

Background: The association between coffee consumption and colorectal cancer risk generally appears null, but recent evidence suggests that risk may vary by coffee type. We examined associations of caffeinated and decaffeinated coffee intake with colorectal cancer risk overall and with colon and rectum separately, among older U.S. men and women.

Methods: In 1999, 47,010 men and 60,051 women with no previous diagnosis of cancer, aged 47-96 years, in the Cancer Prevention Study-II Nutrition Cohort completed a food frequency questionnaire that assessed caffeinated and decaffeinated coffee intake; consumption was updated in 2003. A total of 1829 colorectal cancer cases were verified through June 2015. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking history, alcohol, caffeinated/decaffeinated coffee intake (depending on the model), and other colorectal cancer risk factors.

Results: Consumption of ≥2 cups/day of decaffeinated coffee, compared to no decaffeinated coffee, was associated with lower risk of overall colorectal cancer (HR = 0.82, 95% CI: 0.69-0.96, P-trend = 0.04), colon cancer (HR = 0.82, 95% CI: 0.69-0.99, P-trend = 0.05) and rectal cancer (HR = 0.63, 95% CI: 0.40-0.99, P-trend = 0.17). Consumption of ≥2 cups/day of caffeinated coffee was associated with higher risk of rectal cancer (HR = 1.37, 95% CI: 0.99-1.89, P-trend = 0.04), but not with colorectal or colon cancer.

Conclusion: In this prospective study, higher intake of decaffeinated coffee was associated with lower risk of colorectal, colon, and rectal cancers. Further study on associations of caffeinated and decaffeinated coffee with colorectal cancer risk by subsite is needed.
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http://dx.doi.org/10.1016/j.canep.2020.101730DOI Listing
August 2020

American Cancer Society guideline for diet and physical activity for cancer prevention.

CA Cancer J Clin 2020 07 9;70(4):245-271. Epub 2020 Jun 9.

Cancer Control, American Cancer Society, Atlanta, Georgia.

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
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http://dx.doi.org/10.3322/caac.21591DOI Listing
July 2020

Erythrocyte levels of cadmium and lead and risk of B-cell non-Hodgkin lymphoma and multiple myeloma.

Int J Cancer 2020 12 25;147(11):3110-3118. Epub 2020 Jun 25.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA.

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B-cell NHL (B-NHL) and multiple myeloma, we conducted a nested case-control study among 299 incident B-cell NHLs and 76 MM cases within the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Each case was incidence-density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02-1.33 per 17.6 μg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15-2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B-NHL (RR = 0.89, 95% CI: 0.75-1.06 per 0.37 μg/L [1 SD]), or any B-NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38-0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings.
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http://dx.doi.org/10.1002/ijc.33136DOI Listing
December 2020

Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms.

Int J Cancer 2020 11 25;147(10):2725-2734. Epub 2020 May 25.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)-considered the best marker of total vitamin D exposure-is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 - <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable-adjusted hazard ratios (HRs) for CRC-specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44-3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68-1.22) among cases without Gc2 (P = .0002). The corresponding HRs for all-cause mortality were 1.80 (95% CI 1.24-2.60) among those with Gc2, and 1.12 (95% CI 0.84-1.51) among those without Gc2 (P = .004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.
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http://dx.doi.org/10.1002/ijc.33043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529852PMC
November 2020

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study.

JNCI Cancer Spectr 2020 Feb 15;4(1):pkz083. Epub 2019 Oct 15.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.

Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, = 1.2 × 10). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) ( = .01).

Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.
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http://dx.doi.org/10.1093/jncics/pkz083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050153PMC
February 2020

Validation of self-reported height and weight in a large, nationwide cohort of U.S. adults.

PLoS One 2020 13;15(4):e0231229. Epub 2020 Apr 13.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA.

Background: Height and weight are commonly used metrics in epidemiologic studies to calculate body mass index. Large cohort studies generally assess height and weight by self-report rather than by measurement. The aim of this study was to assess the validity of self-reported height and weight in the Cancer Prevention Study-3 (CPS-3), a large, nationwide cohort recruited by the American Cancer Society between 2006-2013.

Methods: In a subset of CPS-3 participants (n = 2,643), weight and height were assessed at the same time via self-report and in-person measurement. BMI was calculated and classified underweight (<18.5 kg/m2), normal (18.5-<25 kg/m2), overweight (25-<30 kg/m2), or obese (≥30 kg/m2). Self-reported and measured height, weight, and BMI were compared using mean differences and Bland-Altman plots and examined by sex, race/ethnicity, education, marital status, age group, and BMI category.

Results: Men and women slightly overreported height and underreported weight. BMI calculated from self-reported data was lower than for measured data for men and women. In analyses stratified by race/ethnicity, age, education, and marital status, older women and women with less than a college degree overreported height. Approximately 13% of men and 7% of women were misclassified into a lower self-reported BMI category, with misclassification of BMI being greatest in obese men and women.

Conclusions: Overall, height, weight, and BMI were well-reported, and this study further suggests that BMI computed from self-reported weight and height is a valid measure in men and women across different socio-demographic groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231229PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153869PMC
July 2020

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

J Nutr 2020 06;150(6):1566-1578

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA.

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.
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http://dx.doi.org/10.1093/jn/nxaa082DOI Listing
June 2020

Genetic Predictors of Circulating 25-Hydroxyvitamin D and Prognosis after Colorectal Cancer.

Cancer Epidemiol Biomarkers Prev 2020 06 18;29(6):1128-1134. Epub 2020 Mar 18.

Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

Background: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in patients with colorectal cancer have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence colorectal cancer mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and colorectal cancer-specific survival.

Methods: Six genetic variants have been robustly identified to be associated with 25(OH)D levels in genome-wide association studies. On the basis of data from the International Survival Analysis in Colorectal Cancer Consortium, the individual genetic variants and a weighted genetic risk score were tested for association with overall and colorectal cancer-specific survival using Cox proportional hazards models in 7,657 patients with stage I to IV colorectal cancer, of whom 2,438 died from any cause and 1,648 died from colorectal cancer.

Results: The 25(OH)D decreasing allele of SNP rs2282679 ( gene, encodes group-specific component/vitamin D-binding protein) was associated with poorer colorectal cancer-specific survival, although not significant after multiple-testing correction. None of the other five SNPs showed an association. The genetic risk score showed nonsignificant associations with increased overall [HR = 1.54; confidence interval (CI), 0.86-2.78] and colorectal cancer-specific mortality (HR = 1.76; 95% CI, 0.86-3.58). A significant increased risk of overall mortality was observed in women (HR = 3.26; 95% CI, 1.45-7.33; = 0.01) and normal-weight individuals (HR = 4.14; 95% CI, 1.50-11.43, = 0.02).

Conclusions: Our results provided little evidence for an association of genetic predisposition of lower vitamin D levels with increased overall or colorectal cancer-specific survival, although power might have been an issue.

Impact: Further studies are warranted to investigate the association in specific subgroups.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269850PMC
June 2020

Red and Processed Meat, Poultry, Fish, and Egg Intakes and Cause-Specific and All-Cause Mortality among Men with Nonmetastatic Prostate Cancer in a U.S. Cohort.

Cancer Epidemiol Biomarkers Prev 2020 05 4;29(5):1029-1038. Epub 2020 Mar 4.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

Background: Research on the relationship of meat, fish, and egg consumption and mortality among prostate cancer survivors is limited.

Methods: In the Cancer Prevention Study-II Nutrition Cohort, men diagnosed with nonmetastatic prostate cancer between baseline in 1992/1993 and 2015 were followed for mortality until 2016. Analyses of pre- and postdiagnosis intakes of red and processed meat, poultry, fish, and eggs included 9,286 and 4,882 survivors, respectively. Multivariable-adjusted RRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models.

Results: A total of 4,682 and 2,768 deaths occurred during follow-up in pre- and postdiagnosis analyses, respectively. Both pre- and postdiagnosis intakes of total red and processed meat were positively associated with all-cause mortality (quartile 4 vs. 1: RR = 1.13; 95% CI, 1.03-1.25; = 0.02; RR = 1.22; 95% CI, 1.07-1.39; = 0.03, respectively), and both pre- and postdiagnosis poultry intakes were inversely associated with all-cause mortality (quartile 4 vs. 1 RR = 0.90; 95% CI, 0.82-0.98; = 0.04; RR = 0.84; 95% CI, 0.75-0.95; = 0.01, respectively). No associations were seen for prostate cancer-specific mortality, except that higher postdiagnosis unprocessed red meat intake was associated with lower risk.

Conclusions: Higher red and processed meat, and lower poultry, intakes either before or after prostate cancer diagnosis were associated with higher risk of all-cause mortality.

Impact: Our findings provide additional evidence that prostate cancer survivors should follow the nutrition guidelines limiting red and processed meat consumption to improve overall survival. Additional research on the relationship of specific meat types and mortality is needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1426DOI Listing
May 2020

Prospective Association of Energy Balance Scores Based on Metabolic Biomarkers with Colorectal Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2020 05 24;29(5):974-981. Epub 2020 Feb 24.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

Background: Energy balance-related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear.

Methods: We used reduced rank regression to derive three energy balance scores that associate lifestyle factors with combinations of prediagnostic, circulating levels of high-sensitivity C-reactive protein (hsCRP), C-peptide, and hemoglobin A (HbA) among 2,498 participants in the Cancer Prevention Study-II Nutrition Cohort. Among 114,989 participants, we verified 2,228 colorectal cancer cases. We assessed associations of each score with colorectal cancer incidence and by tumor molecular phenotypes using Cox proportional hazards regression.

Results: The derived scores comprised BMI, physical activity, screen time, and 14 food groups, and explained 5.1% to 10.5% of the variation in biomarkers. The HR and 95% confidence interval (CI) for quartile 4 versus 1 of the HbA+C peptide-based score and colorectal cancer was 1.30 (1.15-1.47), the hsCRP-based score was 1.35 (1.19-1.53), and the hsCRP, C-peptide, and HbA-based score was 1.35 (1.19-1.52). The latter score was associated with non-CIMP tumors (HR: 1.59; 95% CI: 1.17-2.16), but not CIMP-positive tumors ( = 0.04).

Conclusions: These results further support hypotheses that systemic biomarkers of metabolic health-inflammation and abnormal glucose homeostasis-mediate part of the relationship between several energy balance-related modifiable factors and colorectal cancer risk.

Impact: Results support cancer prevention guidelines for maintaining a healthful body weight, consuming a healthful diet, and being physically active. More research is needed on these clusters of exposures with molecular phenotypes of tumors.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1382DOI Listing
May 2020

U.S. Dietary Guidelines and Cancer Prevention: Your Input Is Needed!

Cancer Epidemiol Biomarkers Prev 2020 01 16;29(1):257-259. Epub 2019 Dec 16.

The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1158/1055-9965.EPI-19-1456DOI Listing
January 2020

Prediagnostic plasma polyunsaturated fatty acids and the risk of amyotrophic lateral sclerosis.

Neurology 2020 02 3;94(8):e811-e819. Epub 2019 Dec 3.

From the Departments of Nutrition (É.J.O., K.B., J.D.F., A.A.) and Epidemiology (J.E.M., A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health (É.J.O.), College of Medicine, University College Cork, Ireland; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Behavioral and Epidemiology Research Group (M.L.M., V.L.S.), American Cancer Society, Atlanta, GA; Family Medicine and Public Health (A.H.S.), School of Medicine, University of California San Diego; Department of Epidemiology (L.S.), College of Public Health, University of Iowa, Iowa City; and Department of Medicine (J.E.M.) and Channing Division of Network Medicine (J.E.M., A.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Objective: To examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS).

Methods: We identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS.

Results: There was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], for trend = 0.054), but in multivariable models the association was only evident in men.

Conclusions: The majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.
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http://dx.doi.org/10.1212/WNL.0000000000008676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136057PMC
February 2020

Metabolomic Profiles Associated with BMI, Waist Circumference, and Diabetes and Inflammation Biomarkers in Women.

Obesity (Silver Spring) 2020 01 27;28(1):187-196. Epub 2019 Nov 27.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA.

Objective: This study was undertaken to identify metabolites associated with BMI and waist circumference (WC) in women and to determine whether these metabolites are associated with biomarkers of metabolic health.

Methods: Untargeted metabolomic analysis was done on serum from 1,534 women. Metabolites associated with BMI and WC were identified using linear regression with a Bonferroni-corrected P value. Clustered blocks of these metabolites were then defined whose association with the anthropometric measures could be represented by a single metabolite. The association of these representative metabolites with biomarkers for diabetes and inflammation was then determined.

Results: About one-third of 781 metabolites included in the analyses were associated with BMI and/or WC. Associations were found for some novel metabolites, including several sphingolipids, nucleotides, and modified fatty acids. Among metabolites most strongly inversely associated with BMI, the choline-containing plasmalogen (O-16:0/18:1) (β = -0.30, P = 6.62 × 10 ) was also inversely associated with c-peptide and positively associated with adiponectin. Adjustment for BMI attenuated the metabolite-biomarker associations more for hemoglobin A1c (> 100%) and c-peptide (58.8% to > 100%) than for C-reactive protein (10.5%-40.0%) and adiponectin (7.0%-30.4%).

Conclusions: These results add to the list of metabolites associated with adiposity and indicate that some may influence processes that contribute to the development of obesity-related diseases.
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http://dx.doi.org/10.1002/oby.22670DOI Listing
January 2020

Irregularity in breakfast consumption and daily meal timing patterns in association with body weight status and inflammation.

Br J Nutr 2019 11 20;122(10):1192-1200. Epub 2019 Aug 20.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA 30303, USA.

Irregular breakfast consumption and food timing patterns in relation to weight status and inflammation were investigated in a cross-sectional manner among 644 participants in the Cancer Prevention Study-3 Diet Assessment Sub-study. Breakfast consumption, and the individual means and the intra-individual standard deviation (isd) of time at first intake of the day, duration of daily intake window and midpoint of daily intake window were collected via six 24-h recalls and examined in relation to BMI, waist circumference (WC) and inflammation (glycoprotein acetyl (GlycA)). Compared with consuming breakfast on all six recalls, linear regression models showed those who consumed breakfast on 4 or 5 of the days had a 1·29 (95 % CI 0·19, 2·38) and 1·64 (95 % CI 0·12, 3·16) kg/m2 higher BMI; no association was found for consuming breakfast ≤3 d. At 1 h later, the average time of first intake was associated with a 0·44 (95 % CI 0·04, 0·84) kg/m2 higher BMI. A 1-h increase in the isd of first intake was associated with a 1·12 (95 % CI 0·49, 1·75) kg/m2 higher BMI; isd in duration and midpoint of intake window were significant prior to additional adjustment for isd in the first intake. One-hour increases in isd for the first intake time (β: 0·15; 95 % CI 0·04, 0·26) and the midpoint of intake window (β: 0·16; 95 % CI 0·02, 0·31) were associated with higher GlycA. No associations were observed for WC independent of BMI. The results provide evidence that irregularity in breakfast consumption and daily intake timing patterns, particularly early in the day, may be related to weight status and inflammation.
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http://dx.doi.org/10.1017/S0007114519002125DOI Listing
November 2019

Association between grains, gluten and the risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.

Eur J Nutr 2020 Jun 25;59(4):1739-1749. Epub 2019 Jun 25.

Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, Atlanta, GA, 30303, USA.

Purpose: Evidence supports a role of whole grains in colorectal cancer (CRC) prevention, but the association between gluten intake and CRC risk in healthy populations is unclear. We examined the association of grain and gluten intake with risk of CRC overall and by subsite among Cancer Prevention Study-II Nutrition Cohort participants.

Methods: In 1999, 50,118 men and 62,031 women completed food frequency questionnaires assessing grain intake. Gluten intake was estimated using the protein content of grain products. Multivariable-adjusted hazards ratio (HR) and 95% confidence interval (CI) of CRC risk were estimated using Cox proportional hazards regression.

Results: During follow-up through 2013, 1742 verified CRC cases occurred. For the highest vs. lowest quintiles of whole grain intake, HRs (95% CIs) of CRC risk were 0.77 (0.61-0.97; P trend = 0.03) among men and 1.10 (95% CI 0.88-1.36; P trend = 0.14) among women (P interaction by sex = 0.01). Men in the highest vs. lowest quintile of whole grain intake had a 43% lower risk of rectal cancer (HR = 0.57, 95% CI 0.35-0.93, P trend = 0.04). Gluten intake was not associated with CRC risk overall (HR = 1.10, 95% CI 0.93-1.32, P trend = 0.10), but was associated with risk of proximal colon cancer among men and women, combined (HR = 1.37, 95% CI 1.07-1.75, quintile 5 vs. 1, P trend = 0.001) and separately. Refined grains and grain-based sweets were not associated with CRC risk.

Conclusions: We found that higher whole grain intake was associated with lower CRC risk among older US men, but not women. The positive association of gluten intake with the risk of proximal colon cancer deserves further study.
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http://dx.doi.org/10.1007/s00394-019-02032-2DOI Listing
June 2020

Metabolomic markers of healthy dietary patterns in US postmenopausal women.

Am J Clin Nutr 2019 05;109(5):1439-1451

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA.

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.
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http://dx.doi.org/10.1093/ajcn/nqy385DOI Listing
May 2019

Anthropometric factors and risk of myeloid leukaemias and myelodysplastic syndromes: a prospective study and meta-analysis.

Br J Haematol 2019 07 11;186(2):243-254. Epub 2019 Apr 11.

Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.

There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study-II (CPS-II), and a meta-analysis of published cohort studies. Among 152 090 CPS-II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow-up. In CPS-II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99-1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98-1·03) and MDS (HR = 1·03, 95% CI: 0·99-1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta-analysis (n = 7117 myeloid leukaemias), BMI 25-29·9 kg/m (HR  = 1·36, 95% CI: 1·12-1·59) and BMI ≥30 kg/m (HR  = 1·43, 95% CI: 1·18-1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m . Likewise, BMI ≥25 kg/m was positively associated with both AML and CML risk individually in the meta-analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk.
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http://dx.doi.org/10.1111/bjh.15904DOI Listing
July 2019

Prediagnostic plasma metabolomics and the risk of amyotrophic lateral sclerosis.

Neurology 2019 04 29;92(18):e2089-e2100. Epub 2019 Mar 29.

From the Departments of Nutrition (K.B., Z.Z., É.J.O., D.D.W., A.A.) and Epidemiology (L.L., J.E.M., A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health (É.J.O.), College of Medicine, University College Cork, Ireland; Department of Neurology (J.D.B., M.A.S.), Massachusetts General Hospital, Boston; Metabolomics Platform (C.B.C., A.D., S.J., K.A.P.), Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA; Department of Oncology (I.K.), Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Channing Division of Network Medicine (R.S.K., A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Behavioral and Epidemiology Research Group (M.L.M.), American Cancer Society, Atlanta, GA; Department of Physical Medicine and Rehabilitation (S.P.), Spaulding Rehabilitation Hospital and Massachusetts General Hospital; Harvard Medical School (S.P., M.A.S.), Boston, MA; Family Medicine and Public Health (A.H.S.), School of Medicine, University of California San Diego; Epidemiology and Environmental Health, Public Health and Health Professions (J.W.-W.), University at Buffalo, NY; Behavioral and Epidemiology Research Group (Y.W.), American Cancer Society, Atlanta, GA; and Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Objective: To identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS).

Methods: We conducted a global metabolomic study using a nested case-control study design within 5 prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls.

Results: A total of 31 out of 404 identified metabolites were associated with ALS risk ( < 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses.

Conclusions: Although the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset.
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http://dx.doi.org/10.1212/WNL.0000000000007401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512888PMC
April 2019

Reproducibility of non-fasting plasma metabolomics measurements across processing delays.

Metabolomics 2018 09 25;14(10):129. Epub 2018 Sep 25.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.

Introduction: Processing delays after blood collection is a common pre-analytical condition in large epidemiologic studies. It is critical to evaluate the suitability of blood samples with processing delays for metabolomics analysis as it is a potential source of variation that could attenuate associations between metabolites and disease outcomes.

Objectives: We aimed to evaluate the reproducibility of metabolites over extended processing delays up to 48 h. We also aimed to test the reproducibility of the metabolomics platform.

Methods: Blood samples were collected from 18 healthy volunteers. Blood was stored in the refrigerator and processed for plasma at 0, 15, 30, and 48 h after collection. Plasma samples were metabolically profiled using an untargeted, ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. Reproducibility of 1012 metabolites over processing delays and reproducibility of the platform were determined by intraclass correlation coefficients (ICCs) with variance components estimated from mixed-effects models.

Results: The majority of metabolites (approximately 70% of 1012) were highly reproducible (ICCs ≥ 0.75) over 15-, 30- or 48-h processing delays. Nucleotides, energy-related metabolites, peptides, and carbohydrates were most affected by processing delays. The platform was highly reproducible with a median technical ICC of 0.84 (interquartile range 0.68-0.93).

Conclusion: Most metabolites measured by the UPLC-MS/MS platform show acceptable reproducibility up to 48-h processing delays. Metabolites of certain pathways need to be interpreted cautiously in relation to outcomes in epidemiologic studies with prolonged processing delays.
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http://dx.doi.org/10.1007/s11306-018-1429-6DOI Listing
September 2018
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