Table 3.
Odds ratios for breast cancer risk comparing 90th to 10th percentiles of selected metabolite levels^ measured at distant or proximate blood, by ER status of case.
| ER+ (N=585) | ER− (N=91) | ||||||
|---|---|---|---|---|---|---|---|
|
|
|||||||
| Metabolite Name | HMDB ID | Class | Subclass | OR (95% CI)† | p value | OR (95% CI)† | p value |
| Distant Blood | |||||||
|
| |||||||
| hippurate | HMDB0000714 | Benzene and substituted derivatives | Benzoic acids and derivatives | 0.67 (0.50–0.90) | 0.007 | 1.02 (0.57–1.82) | 0.952 |
| N-alpha-acetylarginine | HMDB0004620* | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 0.70 (0.53–0.94) | 0.016 | 0.69 (0.39–1.23) | 0.214 |
| citrulline | HMDB0000904 | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 0.74 (0.55–0.99) | 0.045 | 0.82 (0.46–1.46) | 0.496 |
| C5:1 carnitine | HMDB0002366 | Fatty Acyls | Fatty acid esters | 0.59 (0.44–0.79) | <0.001 | 1.12 (0.61–2.06) | 0.715 |
| C3 carnitine | HMDB0000824 | Fatty Acyls | Fatty acid esters | 0.72 (0.54–0.97) | 0.029 | 1.16 (0.64–2.10) | 0.621 |
| C4 carnitine | HMDB0002013 | Fatty Acyls | Fatty acid esters | 0.69 (0.52–0.92) | 0.012 | 0.91 (0.50–1.64) | 0.748 |
| C5-DC carnitine | HMDB0013130 | Fatty Acyls | Fatty acid esters | 0.70 (0.53–0.93) | 0.015 | 0.94 (0.52–1.68) | 0.823 |
| C34:2 DAG | HMDB0007103* | Fatty Acyls | Lineolic acids and derivatives | 1.50 (1.12–2.02) | 0.007 | 1.49 (0.81–2.78) | 0.203 |
| C36:3 DAG | HMDB0007219* | Fatty Acyls | Lineolic acids and derivatives | 1.35 (1.01–1.80) | 0.040 | 1.29 (0.70–2.39) | 0.419 |
| C32:0 DAG | HMDB0007098* | Glycerolipids | Diacylglycerols | 1.44 (1.06–1.94) | 0.018 | 1.49 (0.80–2.77) | 0.209 |
| C34:1 DAG | HMDB0007102* | Glycerolipids | Diacylglycerols | 1.38 (1.03–1.87) | 0.034 | 1.41 (0.75–2.66) | 0.284 |
| C52:4 TAG | HMDB0005363* | Glycerolipids | Triacylglycerols | 1.43 (1.07–1.90) | 0.015 | 1.22 (0.67–2.25) | 0.518 |
| C50:2 TAG | HMDB0005377* | Glycerolipids | Triacylglycerols | 1.44 (1.06–1.96) | 0.021 | 1.26 (0.67–2.38) | 0.476 |
| C50:1 TAG | HMDB0005360* | Glycerolipids | Triacylglycerols | 1.42 (1.04–1.93) | 0.027 | 1.24 (0.66–2.33) | 0.508 |
| C52:2 TAG | HMDB0005369* | Glycerolipids | Triacylglycerols | 1.38 (1.02–1.87) | 0.035 | 1.25 (0.67–2.36) | 0.479 |
| C50:3 TAG | HMDB0005433* | Glycerolipids | Triacylglycerols | 1.38 (1.02–1.88) | 0.035 | 1.45 (0.78–2.73) | 0.245 |
| C51:1 TAG | HMDB0042104* | Glycerolipids | Triacylglycerols | 1.38 (1.02–1.86) | 0.036 | 1.46 (0.79–2.68) | 0.227 |
| C43:2 TAG | HMDB0043169* | Glycerolipids | Triacylglycerols | 1.37 (1.01–1.85) | 0.041 | 1.46 (0.80–2.67) | 0.220 |
| C55:2 TAG | HMDB0042226* | Glycerolipids | Triacylglycerols | 1.35 (1.00–1.82) | 0.047 | 1.18 (0.64–2.19) | 0.591 |
| C22:5 LPC | HMDB0010403* | Glycerophospholipids | Glycerophosphocholines | 0.58 (0.43–0.77) | <0.001 | 0.71 (0.39–1.27) | 0.248 |
| C18:2 LPC | HMDB0010386* | Glycerophospholipids | Glycerophosphocholines | 0.64 (0.47–0.87) | 0.005 | 0.78 (0.41–1.49) | 0.453 |
| C20:5 LPC | HMDB0010397 | Glycerophospholipids | Glycerophosphocholines | 0.65 (0.48–0.88) | 0.006 | 0.82 (0.43–1.54) | 0.535 |
| C18:1 LPC | HMDB0002815* | Glycerophospholipids | Glycerophosphocholines | 0.68 (0.51–0.91) | 0.011 | 0.96 (0.52–1.74) | 0.889 |
| C18:0 LPC | HMDB0010384 | Glycerophospholipids | Glycerophosphocholines | 0.69 (0.51–0.93) | 0.014 | 1.09 (0.58–2.03) | 0.789 |
| C36:5 PC plasmalogen-B | HMDB0011220* | Glycerophospholipids | Glycerophosphocholines | 0.75 (0.57–0.99) | 0.043 | 0.84 (0.47–1.47) | 0.534 |
| C22:0 LPE | HMDB0011520 | Glycerophospholipids | Glycerophosphoethanolamines | 0.65 (0.48–0.88) | 0.005 | 0.96 (0.51–1.80) | 0.900 |
| C38:6 PE plasmalogen | HMDB0011387* | Glycerophospholipids | Glycerophosphoethanolamines | 0.72 (0.54–0.95) | 0.022 | 0.72 (0.41–1.27) | 0.254 |
| C36:5 PE plasmalogen | HMDB0011410* | Glycerophospholipids | Glycerophosphoethanolamines | 0.73 (0.55–0.97) | 0.028 | 0.84 (0.48–1.47) | 0.542 |
| serotonin | HMDB0000259 | Indoles and derivatives | Tryptamines and derivatives | 1.37 (1.04–1.81) | 0.025 | 1.03 (0.59–1.80) | 0.925 |
| C20:4 LPC | HMDB0010395 | NA | NA | 0.66 (0.50–0.88) | 0.004 | 0.94 (0.52–1.67) | 0.823 |
| thyroxine | HMDB0000248 | NA | NA | 1.50 (1.11–2.04) | 0.009 | 2.16 (1.15–4.13) | 0.018 |
| C20:1 LPE | HMDB0011512* | NA | NA | 0.69 (0.52–0.92) | 0.011 | 0.71 (0.39–1.30) | 0.270 |
| trigonelline | HMDB0000875 | NA | NA | 0.71 (0.53–0.95) | 0.021 | 0.66 (0.37–1.18) | 0.161 |
| carnitine | HMDB0000062 | Organonitrogen compounds | Quaternary ammonium salts | 0.73 (0.54–0.99) | 0.041 | 1.12 (0.60–2.07) | 0.729 |
| acetyl-galactosamine | HMDB0000212 | Organooxygen compounds | Carbohydrates and carbohydrate conjugates | 1.26 (0.95–1.69) | 0.110 | 1.85 (1.04–3.33) | 0.037 |
| 2-methylguanosine | HMDB0005862 | Purine nucleosides | NA | 1.34 (1.00–1.79) | 0.054 | 2.02 (1.13–3.64) | 0.019 |
| C22:5 CE | HMDB0010375* | Steroids and steroid derivatives | Cholesterol esters | 0.52 (0.39–0.70) | <0.001 | 0.65 (0.35–1.18) | 0.160 |
| C20:5 CE | HMDB0006731 | Steroids and steroid derivatives | Cholesterol esters | 0.61 (0.46–0.82) | 0.001 | 0.60 (0.33–1.10) | 0.103 |
| C18:3 CE | HMDB0010370* | Steroids and steroid derivatives | Cholesterol esters | 0.65 (0.49–0.86) | 0.003 | 0.55 (0.30–1.01) | 0.054 |
| C20:4 CE | HMDB0006726 | Steroids and steroid derivatives | Cholesterol esters | 0.67 (0.50–0.89) | 0.006 | 0.77 (0.42–1.38) | 0.374 |
| C18:0 CE | HMDB0010368 | Steroids and steroid derivatives | Cholesterol esters | 0.68 (0.51–0.91) | 0.010 | 0.99 (0.53–1.83) | 0.965 |
| C20:3 CE | HMDB0006736* | Steroids and steroid derivatives | Cholesterol esters | 0.73 (0.55–0.96) | 0.026 | 0.69 (0.38–1.25) | 0.225 |
| C18:1 CE | HMDB0000918* | Steroids and steroid derivatives | Cholesterol esters | 0.72 (0.54–0.97) | 0.030 | 0.77 (0.41–1.42) | 0.404 |
|
| |||||||
| Proximate Blood | |||||||
|
| |||||||
| hippurate | HMDB0000714 | Benzene and substituted derivatives | Benzoic acids and derivatives | 0.64 (0.45–0.91) | 0.014 | 0.52 (0.26–1.03) | 0.062 |
| N1,N12-diacetylspermine | HMDB0002172 | Carboximidic acids and derivatives | Carboximidic acids | 1.46 (1.02–2.08) | 0.038 | 2.33 (1.14–4.81) | 0.020 |
| proline | HMDB0000162 | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 1.52 (1.04–2.21) | 0.029 | 0.89 (0.41–1.91) | 0.760 |
| phenylalanine | HMDB0000159 | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 1.48 (1.03–2.14) | 0.035 | 1.67 (0.80–3.50) | 0.171 |
| isoleucine | HMDB0000172 | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 1.47 (1.00–2.16) | 0.049 | 1.31 (0.62–2.79) | 0.487 |
| C5-DC carnitine | HMDB0013130 | Fatty Acyls | Fatty acid esters | 0.60 (0.42–0.86) | 0.004 | 1.46 (0.72–2.97) | 0.289 |
| C52:0 TAG | HMDB0005365* | Glycerolipids | Triacylglycerols | 1.49 (1.04–2.15) | 0.030 | 0.86 (0.42–1.74) | 0.668 |
| C54:9 TAG | HMDB0010498* | Glycerolipids | Triacylglycerols | 0.68 (0.48–0.98) | 0.037 | 0.60 (0.29–1.23) | 0.160 |
| C58:11 TAG | HMDB0010531* | Glycerolipids | Triacylglycerols | 0.69 (0.48–0.98) | 0.038 | 0.61 (0.29–1.27) | 0.189 |
| C58:9 TAG | HMDB0005463* | Glycerolipids | Triacylglycerols | 0.69 (0.48–0.99) | 0.043 | 0.70 (0.34–1.46) | 0.345 |
| C58:7 TAG | HMDB0005471* | Glycerolipids | Triacylglycerols | 0.68 (0.47–0.99) | 0.044 | 0.55 (0.27–1.10) | 0.093 |
| C56:10 TAG | HMDB0010513* | Glycerolipids | Triacylglycerols | 0.69 (0.49–0.99) | 0.045 | 0.55 (0.26–1.15) | 0.113 |
| C58:10 TAG | HMDB0005476* | Glycerolipids | Triacylglycerols | 0.70 (0.49–0.99) | 0.046 | 0.67 (0.32–1.37) | 0.272 |
| C52:1 TAG | HMDB0005367* | Glycerolipids | Triacylglycerols | 1.45 (1.01–2.09) | 0.047 | 0.83 (0.41–1.70) | 0.614 |
| tryptophan | HMDB0000929 | Indoles and derivatives | Indolyl carboxylic acids and derivatives | 1.56 (1.09–2.23) | 0.015 | 0.98 (0.49–1.97) | 0.956 |
| guanosine | HMDB0000133 | Purine nucleosides | NA | 1.45 (1.02–2.06) | 0.039 | 0.71 (0.35–1.42) | 0.332 |
| C22:0 Ceramide (d18:1) | HMDB0004952 | Sphingolipids | Ceramides | 1.50 (1.05–2.16) | 0.027 | 1.28 (0.63–2.59) | 0.488 |
| C24:1 Ceramide (d18:1) | HMDB0004953* | Sphingolipids | Ceramides | 1.48 (1.03–2.13) | 0.035 | 1.26 (0.61–2.6) | 0.533 |
| C16:0 Ceramide (d18:1) | HMDB0004949 | Sphingolipids | Ceramides | 1.48 (1.02–2.15) | 0.037 | 1.89 (0.95–3.82) | 0.071 |
| C22:5 CE | HMDB0010375* | Steroids and steroid derivatives | Cholesteryl esters | 0.69 (0.49–0.98) | 0.040 | 1.08 (0.56–2.10) | 0.814 |
| hydroxyproline | HMDB0000725 | Carboxylic acids and derivatives | Amino acids, peptides, and analogues | 0.77 (0.54–1.10) | 0.157 | 2.03 (1.01–4.15) | 0.048 |
| C5:1 carnitine | HMDB0002366 | Fatty Acyls | Fatty acid esters | 0.80 (0.55–1.14) | 0.218 | 2.44 (1.19–5.07) | 0.015 |
| C45:0 TAG | HMDB0042093* | Glycerolipids | Triacylglycerols | 1.16 (0.80–1.67) | 0.465 | 0.67 (0.33–1.34) | 0.039 |
| C22:0 LPE | HMDB0011520 | Glycerophospholipids | Glycerophosphoethanolamines | 0.96 (0.66–1.39) | 0.818 | 2.39 (1.16–5.01) | 0.018 |
| deoxyguanosine | HMDB0000085 | NA | NA | 1.18 (0.83–1.68) | 0.346 | 0.47 (0.23–0.98) | 0.043 |
| methyl N-methylanthra-nilate | HMDB0034169 | NA | NA | 1.10 (0.78–1.55) | 0.580 | 0.50 (0.25–0.98) | 0.045 |
| kynurenic acid | HMDB0000715 | Quinolines and derivatives | Quinoline carboxylic acids | 0.97 (0.67–1.41) | 0.888 | 2.14 (1.03–4.5) | 0.041 |
^
Selected metabolites are those with <10% missingness and a nominal p<0.05 for either ER+ or ER− breast cancers (those identified as significant in ER− breast cancers are in bold). Missing values were imputed with 1/2 the minimum value. Results sorted by class, subclass, and p-value for fully adjusted model. Metabolites in bold represent those chosen as top hits for ER− breast cancer.
†
Multivariate unconditional logistic regression model adjusted for: BMI at age 18, weight change since age 18, age at menarche, combined age at first birth and parity, breastfeeding history, history of benign breast disease, family history of breast cancer, alcohol use (g/day), activity level (met hrs/week). P values are nominal p-values before correction for multiple testing.
*
Representative HMDBID