Dataset Information

A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study.

ABSTRACT: Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We used Lasso to further select metabolites for prediction models of adiposity measures, which we used to calculate metabolic scores representing metabolic obesity. In an independent set of 212 advanced prostate cancer cases (T3b/T4/N1/M1 or lethal during follow-up) and 212 controls, we used logistic regression to evaluate the associations between adiposity measures and metabolic scores with risk of advanced disease. All adiposity measures were associated with higher blood levels of carnitines (Pearson r range, 0.16 to 0.18) and lower levels of glutamine (r = -0.19) and glycine (r, -0.29 to -0.20), in addition to alterations in various lipids. No adiposity measure or metabolic score was associated with risk of advanced prostate cancer (e.g., odds ratio for a 5 kg/m2 increase in BMI 0.96 (95% CI: 0.73, 1.27) and BMI metabolic score 1.18 (95% CI: 0.57, 2.48)). BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. Neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer.

SUBMITTER: Dickerman BA

PROVIDER: S-EPMC7142752 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study.

Dickerman Barbra A BA Ebot Ericka M EM Healy Brian C BC Wilson Kathryn M KM Eliassen A Heather AH Ascherio Alberto A Pernar Claire H CH Zeleznik Oana A OA Vander Heiden Matthew G MG Clish Clary B CB Giovannucci Edward E Mucci Lorelei A LA

Metabolites 20200310 3

Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We ...[more]

PMID: 32164144

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Project description:Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI ? 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction <?0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI ? 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men ? 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations between the risk of various prostate cancer subtypes and multiple anthropometric measures at different ages in men. Tallness was confirmed to be associated with an elevated risk of advanced prostate cancer, particularly fatal disease. The extent to which body weight influenced risk varied according to factors such as age and disease subtype.

Project description:Background:Many dietary indexes exist for chronic disease prevention, but the optimal dietary pattern for colorectal cancer prevention is unknown. Objective:We sought to determine associations between adherence to various dietary indexes and incident colorectal cancer in 2 prospective cohort studies. Design:We followed 78,012 women in the Nurses' Health Study and 46,695 men in the Health Professionals Follow-up Study from 1986 and 1988, respectively, until 2012. We created dietary index scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index-2010 (AHEI-2010) and used Cox regression to estimate HRs and 95% CIs for risk of colorectal cancer (CRC) and by anatomic subsite. We also conducted latency analyses to examine associations between diet and CRC risk during different windows of exposure. We conducted analyses in men and women separately, and subsequently pooled these results in a random-effects meta-analysis. Results:We documented 2690 colorectal cancer cases. Pooled multivariable HRs for colorectal cancer risk comparing the highest to lowest quintile of diet scores were 0.89 (95% CI: 0.74, 1.08; P-trend = 0.10) for DASH, 0.89 (95% CI: 0.73, 1.10; P-trend = 0.31) for AMED, and 0.95 (95% CI: 0.83, 1.09; P-trend = 0.56) for AHEI-2010 (P-heterogeneity ? 0.07 for all). In sex-specific analyses, we observed stronger associations in men for all dietary indexes (DASH: multivariable HR = 0.81, 95% CI: 0.66, 0.98; P-trend = 0.003; AMED: multivariable HR = 0.80, 95% CI: 0.65, 0.98; P-trend = 0.02; AHEI-2010: multivariable HR = 0.88, 95% CI: 0.72, 1.07; P-trend = 0.04) than in women (multivariable HRs range from 0.98 to 1.01). Conclusions:Adherence to the DASH, AMED, and AHEI-2010 diets was inversely associated with colorectal cancer risk in men. These diets were not associated with colorectal cancer risk in women. This observational study was registered at http://www.clinicaltrials.gov as NCT03364582.

Dataset Information

A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study.

Publications

A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study.

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