Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.

BACKGROUND: Black Americans suffer disparities in risk for cardiometabolic and other chronic diseases. Findings from the Adventist Health Study-2 (AHS-2) cohort have shown associations of plant-based dietary patterns and healthy lifestyle factors with prevention of such diseases. Hence, it is likely that racial differences in metabolic profiles correlating with disparities in chronic diseases are explained largely by diet and lifestyle, besides social determinants of health. METHODS: Untargeted plasma metabolomics screening was performed on plasma samples from 350 participants of the AHS-2, including 171 Black and 179 White participants, using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a global platform of 892 metabolites. Differences in metabolites or biochemical subclasses by race were analyzed using linear regression, considering various models adjusted for known confounders, dietary and/or other lifestyle behaviors, social vulnerability, and psychosocial stress. The Storey permutation approach was used to adjust for false discovery at FDR < 0.05. RESULTS: Linear regression revealed differential abundance of over 40% of individual metabolites or biochemical subclasses when comparing Black with White participants after adjustment for false discovery (FDR < 0.05), with the vast majority showing lower abundance in Blacks. Associations were not appreciably altered with adjustment for dietary patterns and socioeconomic or psychosocial stress. Metabolite subclasses showing consistently lower abundance in Black participants included various lipids, such as lysophospholipids, phosphatidylethanolamines, monoacylglycerols, diacylglycerols, and long-chain monounsaturated fatty acids, among other subclasses or lipid categories. Among all biochemical subclasses, creatine metabolism exclusively showed higher abundance in Black participants, although among metabolites within this subclass, only creatine showed differential abundance after adjustment for glomerular filtration rate. Notable metabolites in higher abundance in Black participants included methyl and propyl paraben sulfates, piperine metabolites, and a considerable proportion of acetylated amino acids, including many previously found associated with glomerular filtration rate. CONCLUSIONS: Differences in metabolic profiles were evident when comparing Black and White participants of the AHS-2 cohort. These differences are likely attributed in part to dietary behaviors not adequately explained by dietary pattern covariates, besides other environmental or genetic factors. Alterations in these metabolites and associated subclasses may have implications for the prevention of chronic diseases in Black Americans.

Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2.

BACKGROUND: Prostate cancer is the most common noncutaneous cancer in American males. Causal links between dairy, or dietary calcium, and this cancer are considered suggestive but limited. OBJECTIVES: To evaluate these associations in a large North American cohort, including many with no (or very low) dairy intake and much calcium from nondairy sources. METHODS: A prospective cohort study of 28,737 Seventh-day Adventist men in the United States and Canada, of whom 6389 were of black ethnicity. Diet was measured by FFQ, and 275 male participants also provided repeated 24-h dietary recalls as a calibration substudy. Incident cancers were mainly found by matching with cancer registries. Analyses used multivariable proportional hazards regressions and regression calibration for some analyses. RESULTS: In total, 1254 (190 advanced) incident prostate cancer cases were found during an average 7.8 y of follow-up. Men at the 90th percentile of dairy intake (430 g/d) compared with the 10th percentile (20.2 g/d) had higher prostate cancer risk (HR: 1.27; 95% CI: 1.12, 1.43). Similar findings, comparing the same g/d intakes, were demonstrated for advanced prostate cancers (HR: 1.38; 95% CI: 1.02, 1.88), for nonadvanced cases (HR: 1.27; 95% CI: 1.11, 1.45), in black participants (HR: 1.24; 95% CI: 0.98, 1.58), and when excluding vegan participants (HR: 1.22; 95% CI: 1.03, 1.43). Calibrated dairy (g/d) regressions (all participants and all prostate cancers), adjusting for dietary measurement error, found a HR of 1.75 (95% CI: 1.32, 2.32). Comparing 90th percentile intake to zero intakes (uncalibrated), the HR was 1.62 (95% CI: 1.26, 2.05). There was no evidence of an effect of higher (905 mg/d) compared with lower (349 mg/d) intakes of nondairy calcium (HR: 1.16; 95% CI: 0.94, 1.44). CONCLUSIONS: Men with higher intake of dairy foods, but not nondairy calcium, had a higher risk of prostate cancer compared with men having lower intakes. Associations were nonlinear, suggesting greatest increases in risk at relatively low doses.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.