Abstract 1954: Black-White differences in prospective serum metabolites and biochemical pathways associated with prostate cancer risk in a COMETS consortium project
Authors: Lim Jungeun , Hong Grace , Layne Tracy M. , Haiman Chris , Marchand Loic Le , Weinstein Stephanie J. , Huang Jiaqi , Albanes Demetrius 
Published: April 2023

Prostate cancer incidence and mortality rates are substantially higher in Black men as compared with White men. It is unclear which exposures and biochemical pathways may explain this racial disparity. We examined the metabolomic profiles of prostate cancer risk by race within a subset of studies from the COnsortium of METabolomics Studies (COMETS). A meta-analysis of six cohort-based studies including 1,769 prostate cancer case-control sets and 831 serum metabolites was conducted using the multivariable logistic regression and random effects models. Overall, 11 metabolites were significantly associated with prostate cancer risk, including L-cystine (1-SD OR=0.77; P=0.009) and biliverdin (1-SD OR=1.12; P=0.017). The race-stratified analysis of chemical classes revealed that lipids were positively associated with prostate cancer risk only in White men, whereas amino acids were associated inversely primarily in Black men. The latter included metabolites related to tryptophan, lysine, and phenylalanine metabolism; e.g., the strongest metabolite being alpha-N-phenylacetyl-L-glutamine (1-SD OR=0.81; P=0.003), which is produced by Clostridial anaerobic bacteria in the gut. Lipids related to fatty acid metabolism were associated with higher prostate cancer risk in both Black and White men (e.g., docosahexaenoylcholine and 3-hydroxybutyroylglycine), and alpha-tocopherol was inversely associated in White men (1-SD OR=0.69; P=0.011). For other races combined, N-acetyltryptophan (1-SD OR=0.04; P=0.025) showed the strongest metabolite-risk association. To our knowledge, this is the first metabolomic meta-analysis of prostate cancer risk which provides evidence of biochemical etiologic differences relevant to the Black-White disease disparity.

Table 1. Race-stratified meta-analysis estimates of prostate cancer risk by chemical class a White participants Chemical class # Metabolites P-value OR (95% CI) I2 (%) Amino acids 188 0.226 1.005 (0.997-1.013) 15.7 Carbohydrates 24 0.495 1.003 (0.994-1.012) 0.0 Cofactors and vitamins 30 0.442 0.998 (0.991-1.004) 0.0 Energy metabolites 11 0.843 0.991 (0.906-1.084) 34.1 Lipids 339 &lt;0.001 1.016 (1.010-1.021) 17.9 Nucleotides 34 0.197 1.016 (0.992-1.041) 10.4 Peptides 45 0.077 1.015(0.998-1.033) 42.6 Xenobiotics 149 0.233 1.000(1.000-1.000) 0.0 Black participants Chemical class # Metabolites P-value OR (95% CI) I2 (%) Amino acids 176 &lt;0.001 0.970 (0.959-0.981) 1.1 Carbohydrates 21 0.025 0.959 (0.925-0.995) 25.3 Cofactors and vitamins 27 0.178 0.992 (0.980-1.004) 0.0 Energy metabolites 10 0.951 1.001 (0.963-1.041) 0.0 Lipids 311 0.843 1.000 (0.996-1.003) 0.0 Nucleotides 30 0.321 1.007 (0.993-1.022) 0.0 Peptides 44 0.727 0.997 (0.982-1.013) 0.0 Xenobiotics 131 0.059 0.999 (0.999-1.000) 0.0 Asian, Hispanic, and Pacific Islander participants Chemical class # Metabolites P-value OR (95% CI) I2 (%) Amino acids 175 0.318 0.964 (0.896-1.036) 0.0 Carbohydrates 21 0.311 0.920 (0.784-1.081) 0.0 Cofactors and vitamins 27 0.530 0.928 (0.793-1.085) 0.0 Energy metabolites 10 0.558 1.281 (0.560-2.930) 25.0 Lipids 324 0.982 1.000 (0.985-1.015) 0.0 Nucleotides 30 0.355 1.146 (0.858-1.530) 0.0 Peptides 44 0.838 1.017 (0.866-1.195) 0.0 Xenobiotics 139 0.240 1.002 (0.998-1.006) 0.0 a Identified metabolites measured in at least 3 studies were included.

Citation Format: Jungeun Lim, Grace Hong, Tracy M. Layne, Chris Haiman, Loic Le Marchand, Stephanie J. Weinstein, Jiaqi Huang, Demetrius Albanes. Black-White differences in prospective serum metabolites and biochemical pathways associated with prostate cancer risk in a COMETS consortium project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1954.