Table 3.
Gene-set analysis (GSA) and principal components analysis (PCA) for the association between chemical sub-classes of serum metabolites and lethal prostate cancer risk in the ATBC Study a
| Sub-class pathway | No. of contributing metabolites |
GSA analysis | PCA analysis | |||
|---|---|---|---|---|---|---|
| P-value | GSA q-value | OR (95% CI) for pattern score b |
P-value | q-value | ||
| Overall lethal prostate cancer | ||||||
| Dipeptide | 9 | <0.0001 | <0.001 | 1.36 (1.17, 1.58) | 5.8×10−5 | 0.0012 |
| Pyrimidine metabolism, uracil containing | 10 | <0.0001 | <0.001 | 1.32 (1.16, 1.50) | 3.7×10−5 | 0.0012 |
| Gamma-glutamyl amino acid | 16 | 0.002 | 0.013 | 1.20 (1.05, 1.37) | 0.0093 | 0.074 |
| Glycine, serine and threonine metabolism | 9 | 0.006 | 0.029 | 1.10 (0.97, 1.25) | 0.12 | 0.40 |
| Polyunsaturated fatty acid (n3 and n6) | 14 | 0.008 | 0.031 | 1.17 (1.02, 1.33) | 0.022 | 0.12 |
| Aminosugar metabolism | 5 | 0.027 | 0.087 | 1.18 (1.03, 1.35) | 0.017 | 0.12 |
| Androgenic steroids | 21 | 0.033 | 0.092 | 1.08 (0.96, 1.21) | 0.23 | 0.46 |
| Fatty acid, dicarboxylate | 23 | 0.038 | 0.092 | 1.14 (1.004, 1.29) | 0.044 | 0.17 |
| Endocannabinoid | 11 | 0.049 | 0.10 | 1.16 (1.02, 1.33) | 0.025 | 0.12 |
| Time to prostate cancer death c: 0–18 y | ||||||
| Pyrimidine metabolism, uracil containing | 10 | 0.001 | 0.031 | 1.35 (1.12, 1.64) | 0.002 | 0.044 |
| Dipeptide | 9 | 0.002 | 0.031 | 1.36 (1.13, 1.64) | 0.001 | 0.044 |
| Fibrinogen cleavage peptide | 5 | 0.006 | 0.055 | 0.78 (0.66, 0.93) | 0.0060 | 0.052 |
| Glutathione metabolism | 7 | 0.007 | 0.055 | 0.78 (0.65, 0.93) | 0.0054 | 0.052 |
| Pyrimidine metabolism, cytidine containing | 5 | 0.015 | 0.094 | 0.77 (0.65, 0.93) | 0.0049 | 0.052 |
| Gamma-glutamyl amino acid | 16 | 0.022 | 0.10 | 1.20 (1.02, 1.41) | 0.027 | 0.17 |
| Polyunsaturated fatty acid (n3 and n6) | 14 | 0.023 | 0.10 | 1.23 (1.02, 1.49) | 0.029 | 0.17 |
| Fatty acid, dicarboxylate | 23 | 0.033 | 0.13 | 1.19 (0.997, 1.43) | 0.054 | 0.26 |
| Time to prostate cancer death c: >18 y | ||||||
| Pyrimidine metabolism, uracil containing | 10 | 0.008 | 0.32 | 1.29 (1.08, 1.54) | 0.006 | 0.21 |
| Dipeptide | 9 | 0.011 | 0.32 | 1.36 (1.06, 1.76) | 0.017 | 0.30 |
| Aminosugar metabolism | 5 | 0.077 | 0.94 | 1.20 (0.98, 1.47) | 0.075 | 0.54 |
| Fibrinogen cleavage peptide | 5 | 0.082 | 0.94 | 0.84 (0.68, 1.03) | 0.099 | 0.54 |
| Histidine metabolism | 14 | 0.14 | 0.94 | 1.12 (0.94, 1.33) | 0.21 | 0.54 |
| Endocannabinoid | 11 | 0.15 | 0.94 | 1.17 (0.96, 1.41) | 0.12 | 0.54 |
Abbreviations: OR = odds ratio, CI = confidence interval, s.d. = standard deviation, ATBC = Alpha-Tocopherol, Beta-Carotene Cancer Prevention, ICD = International Classification of Diseases.
Statistical significance of pathway analysis is defined as false discovery rate < 0.15 and P-value <0.05. The GSA Sub-class pathway analysis for overall lethal prostate cancer is based on 523 cases and 523 controls, for time to prostate cancer death (0–18 years) analysis is based on 263 cases and 263 controls. GSA and PCA q-value calculations are based on 59 tests.
Odds ratio per 1 s.d. increase in pattern score derived from PCA analysis (mean = 0, s.d. = 1). Lethal prostate cancer was defined as cases who died of prostate cancer (ICD-9=185 or ICD-10=C61).
Time to prostate cancer death: time (median split) from blood collection to prostate cancer death for cases, and their matched controls.