Table 2.
Association of serum metabolites with PFOA in a cross-sectional analysis of 3,647 participants from eight nested case-control serum metabolomic studies from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (metabolites ordered by chemical class and pathway)
| All Subjects | Adjustment with PFOSa | |||||||
|---|---|---|---|---|---|---|---|---|
| Metabolite (HMDB ID) | Chemical class | Sub-pathway | Overall effect estimate (β) (95% CI) |
P-value | P heterogeneity by study |
Overall effect estimate (β) (95% CI) |
P-value | P heterogeneity by study |
| Cysteine-S-sulfate (HMDB00731) | Amino Acid | Methionine, Cysteine, SAM and Taurine Metabolism | 0.07 (0.04,0.09) | 5.18E-07 | 0.41 | 0.06 (0.04,0.09) | 6.52E-06 | 0.12 |
| 1,5-Anhydrosorbitol (HMDB02712) | Carbohydrate | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | 0.07 (0.05,0.1) | 8.00E-08 | 0.50 | 0.05 (0.02,0.07) | 2.43E-05 | 0.64 |
| Trigonelline (HMDB00875) | Cofactors and Vitamins | Nicotinate and Nicotinamide Metabolism | 0.04 (0.02,0.05) | 3.94E-08 | 0.53 | 0.02 (0.01,0.03) | 4.84E-04 | 0.76 |
| 4-androsten-3alpha,17alpha-diol monosulfate (2) or Androstenediol (3alpha, 17alpha) monsulfate (2) | Lipid | Androgenic Steroids | 0.03 (0.02,0.04) | 3.13E-06 | 0.53 | 0.02 (0,0.03) | 0.01 | 0.41 |
| 5alpha-Androstan-3alpha,17beta-diol disulfate | Lipid | Androgenic Steroids | 0.05 (0.03,0.07) | 2.38E-05 | 0.02 | 0.02 (0.01,0.03) | 0.003 | 0.26 |
| SM(d18:0/18:0) (HMDB12087) | Lipid | Dihydrosphingomyelins | 0.20 (0.12,0.27) | 8.61E-08 | 0.67 | 0.08 (0.02,0.13) | 0.005 | 0.89 |
| SM(d18:0/20:0) | Lipid | Dihydrosphingomyelins | 0.21 (0.15,0.28) | 4.13E-10 | 0.61 | 0.08 (0.03,0.13) | 0.002 | 0.72 |
| Lignoceroylcarnitine (C24) | Lipid | Fatty Acid Metabolism | 0.16 (0.09,0.23) | 6.23E-06 | 0.58 | 0.03 (−0.03,0.09) | 0.38 | 0.25 |
| Hexanoylcarnitine (HMDB00705) | Lipid | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | 0.07 (0.04,0.11) | 3.47E-05 | 0.29 | 0.04 (0.02,0.07) | 2.91E-04 | 0.46 |
| 9-Decenoylcarnitine | Lipid | Fatty Acid Metabolism (Acyl Carnitine, Monounsaturat | 0.09 (0.05,0.13) | 2.98E-05 | 0.11 | 0.04 (0.02,0.06) | 1.57E-04 | 0.44 |
| 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (3-CMPFP) | Lipid | Fatty Acid, Dicarboxylate | 0.16 (0.12,0.2) | 1.11E-17 | 0.42 | 0.04 (0.01,0.07) | 0.01 | 0.81 |
| Eicosanodioate | Lipid | Fatty Acid, Dicarboxylate | 0.12 (0.07,0.16) | 8.66E-07 | 0.37 | 0.02 (−0.02,0.05) | 0.37 | 0.33 |
| Maleic acid (HMDB00176) | Lipid | Fatty Acid, Dicarboxylate | 0.05 (0.03,0.08) | 4.81E-06 | 0.92 | 0.03 (0.01,0.04) | 0.004 | 0.89 |
| (R)-2-Hydroxycaprylic acid (HMDB02264) | Lipid | Fatty Acid, Monohydroxy | 0.1 (0.06,0.13) | 8.36E-07 | 0.28 | 0.03 (0,0.06) | 0.08 | 0.20 |
| SM(d18:1/18:0) (HMDB01348) | Lipid | Sphingomyelins | 0.25 (0.16,0.34) | 2.01E-08 | 0.49 | 0.06 (−0.01,0.12) | 0.09 | 0.45 |
| SM(d18:1/18:1(9Z)) (HMDB12101) | Lipid | Sphingomyelins | 0.24 (0.16,0.32) | 1.10E-09 | 0.35 | 0.12 (0.06,0.17) | 1.60E-05 | 0.93 |
| Glycosyl-N-behenoyl-sphingadienine (d18:2/22:0)* | Lipid | Hexosylceramides (HCER) | 0.26 (0.14,0.37) | 9.62E-06 | 0.24 | 0.06 (−0.02,0.13) | 0.13 | 0.88 |
| Lactosylceramide (d18:1/24:1(15Z)) | Lipid | Lactosylceramides (LCER) | 0.22 (0.12,0.32) | 0.00003 | 0.71 | 0.01 (−0.06,0.09) | 0.72 | 0.52 |
| 1-linoleoylglycerophosphoinositol* or 1-linoleoyl-GPI (18:2)* | Lipid | Lysophospholipid | 0.13 (0.07,0.19) | 6.48E-06 | 0.04 | 0.04 (0,0.08) | 0.04 | 0.15 |
| 3 beta-Hydroxy-5-cholestenoate | Lipid | Sterol | 0.24 (0.14,0.33) | 4.74E-07 | 0.15 | 0.08 (0.02,0.13) | 0.004 | 0.38 |
| Uric acid (HMDB00289) | Nucleotide | Purine Metabolism, (Hypo)Xanthine/Inosine containing | 0.28 (0.16,0.41) | 1.23E-05 | 0.02 | 0.12 (0.05,0.19) | 0.0009 | 0.25 |
| 3-methylcytidine | Nucleotide | Pyrimidine Metabolism, Cytidine containing | 0.15 (0.08,0.22) | 3.93E-05 | 0.09 | 0.05 (0,0.1) | 0.04 | 0.13 |
| Leucyl-Alanine (HMDB28922) | Peptide | Dipeptide | 0.07 (0.04,0.11) | 4.31E-05 | 0.33 | 0.05 (0.02,0.07) | 2.25E-04 | 0.96 |
| O-methoxycatechol-O-sulphate (HMDB60013) | Xenobiotics | Benzoate Metabolism | 0.05 (0.03,0.07) | 4.38E-06 | 0.42 | 0.02 (0,0.04) | 0.02 | 0.27 |
| 3,5-dichloro-2,6-dihydroxybenzoic acid | Xenobiotics | Chemical | 0.48 (0.35,0.61) | 6.82E-13 | 0.003 | 0.06 (−0.16,0.28) | 0.6 | 9.09E-10 |
| 3-bromo-5-chloro-2,6-dihydroxybenzoic acid | Xenobiotics | Chemical | 0.39 (0.23,0.55) | 2.29E-06 | 0.003 | 0.08 (−0.21,0.36) | 0.6 | 9.63E-10 |
| 4-hydroxychlorothalonil | Xenobiotics | Chemical | 0.21 (0.13,0.3) | 1.26E-06 | 1.18E-06 | 0.00 (−0.06,0.06) | 0.96 | 0.0005 |
| Quinic acid (HMDB03072) | Xenobiotics | Food Component/Plant | 0.03 (0.01,0.04) | 6.88E-06 | 0.32 | 0.01 (0,0.02) | 0.002 | 0.63 |
| 1,3,7-Trimethyluric acid (HMDB02123) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.04) | 7.40E-10 | 0.70 | 0.01 (0.01,0.02) | 0.001 | 0.60 |
| 1,3-Dimethyluric acid (HMDB01857) | Xenobiotics | Xanthine Metabolism | 0.02 (0.01,0.03) | 5.23E-07 | 0.66 | 0.01 (0,0.02) | 0.03 | 0.76 |
| 1,7-Dimethyluric acid (HMDB11103) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.04) | 1.32E-09 | 0.86 | 0.01 (0,0.02) | 0.003 | 0.43 |
| 1-Methyluric acid (HMDB03099) | Xenobiotics | Xanthine Metabolism | 0.04 (0.02,0.05) | 1.37E-06 | 0.36 | 0.01 (0,0.02) | 0.01 | 0.71 |
| 1-Methylxanthine (HMDB10738) | Xenobiotics | Xanthine Metabolism | 0.04 (0.02,0.05) | 2.31E-09 | 0.82 | 0.01 (0.01,0.02) | 0.002 | 0.49 |
| 5-Acetylamino-6-amino-3-methyluracil (HMDB04400) | Xenobiotics | Xanthine Metabolism | 0.02 (0.01,0.03) | 3.71E-08 | 0.52 | 0.01 (0,0.02) | 0.01 | 0.61 |
| Caffeine (HMDB01847) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.04) | 3.51E-10 | 0.63 | 0.01 (0,0.02) | 0.02 | 0.16 |
| Paraxanthine (HMDB01860) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.05) | 1.52E-10 | 0.86 | 0.02 (0,0.03) | 0.01 | 0.29 |
| Theobromine (HMDB02825) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.04) | 2.71E-05 | 0.60 | 0.01 (0,0.03) | 0.11 | 0.15 |
| Theophylline (HMDB01889) | Xenobiotics | Xanthine Metabolism | 0.03 (0.02,0.05) | 1.96E-10 | 0.96 | 0.02 (0.01,0.02) | 0.001 | 0.49 |
PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate; HMDB, Human Metabolome Database
Results are based on a population of 3,647 participants [prostate cancer among non-Hispanic Black men (cases=220, controls=219), prostate cancer (cases=356, controls=372), esophageal cancer (cases=131, controls=127), glioma cancer (cases=161, controls=163), breast cancer (cases=604, controls=605), pancreatic cancer (cases=107, controls=103), endometrial cancer (cases=190, controls=191), and multivitamin exposure study (multivitamin users=49, non-users=49)]. Within each specific study, the association between metabolite levels and PFOA was modeled using linear regression, adjusted for age at specimen collection, race/ethnicity, body mass index, smoking status, case status, study center, year of specimen collection. Sex was additionally adjusted for studies of pancreatic cancer, glioma, and multivitamin study. The combined model was conducted using random effects meta-analysis.
PFOS was further adjusted in linear regression models.
Only the metabolites that met the Bonferroni corrected threshold of statistical significance in the combined models (0.05/1,100 = 4.55x10−5) are shown here.
Metabolites with a single asterisk (*) have identification level 2 no standards or matching spectra were available for them.