Table 6.
Four-way decomposition of each mediator of the associations between BaP and breast cancer risk
| Mediation | Effect | Estimate (CI 95%) | P value | Proportion | P value |
|---|---|---|---|---|---|
| Albumin | TE | 0.0143 (− 0.2134, 0.2421) | 0.902 | ||
| CDE | 0.0095 (− 0.2189, 0.2380) | 0.935 | 66.4% | 0.813 | |
| INTref | 0.0013 (− 0.0175, 0.0201) | 0.890 | 9.3% | 0.928 | |
| INTmed | − 0.0007 (− 0.0101, 0.0088) | 0.889 | − 4.7% | 0.927 | |
| PIE | 0.0042 (− 0.0096, 0.0179) | 0.553 | 29.0% | 0.903 | |
| O_M | 24.3% | 0.903 | |||
| CRP | TE | 0.0530 (− 0.2032, 0.3091) | 0.685 | ||
| CDE | 0.0705 (− 0.1792, 0.3201) | 0.580 | 133.0% | 0.216 | |
| INTref | − 0.0160 (− 0.0737, 0.0418) | 0.587 | − 30.2% | 0.769 | |
| INTmed | 0.0019 (− 0.0057, 0.0094) | 0.629 | 3.5% | 0.779 | |
| PIE | − 0.0034 (− 0.0132, 0.0064) | 0.501 | − 6.3% | 0.736 | |
| O_M | − 2.8% | 0.762 | |||
| Triglycerides | TE | 0.0287 (− 0.2204, 0.2778) | 0.821 | ||
| CDE | 0.0255 (− 0.2236, 0.2746) | 0.841 | 88.9% | 0.127 | |
| INTref | 0.0027 (− 0.0161, 0.0215) | 0.778 | 9.4% | 0.858 | |
| INTmed | − 0.0002 (− 0.0027, 0.0022) | 0.839 | − 0.9% | 0.877 | |
| PIE | 0.0007 (− 0.0046, 0.0061) | 0.789 | 2.5% | 0.861 | |
| O_M | 1.7% | 0.865 | |||
| Cholesterol | TE | 0.0935 (− 0.1848, 0.3717) | 0.510 | ||
| CDE | 0.0973 (− 0.1822, 0.3768) | 0.495 | 104.0% | < 0.001 | |
| INTref | 0.0006 (− 0.0191, 0.0204) | 0.949 | 0.7% | 0.949 | |
| INTmed | − 0.0056 (− 0.0172, 0.0059) | 0.339 | − 6.0% | 0.547 | |
| PIE | 0.0012 (− 0.0074, 0.0099) | 0.783 | 1.3% | 0.793 | |
| O_M | − 4.7% | 0.580 | |||
| HDL cholesterol | TE | 0.0977 (− 0.2007, 0.3962) | 0.521 | ||
| CDE | 0.1207 (− 0.1885, 0.4299) | 0.444 | 123.5% | < 0.001 | |
| INTref | − 0.0047 (− 0.0451, 0.0357) | 0.821 | − 4.8% | 0.828 | |
| INTmed | − 0.0262 (− 0.0599, 0.0076) | 0.129 | − 26.8% | 0.487 | |
| PIE | 0.0078 (− 0.0287, 0.0443) | 0.674 | 8.0% | 0.705 | |
| O_M | − 18.7% | 0.562 | |||
| LDL cholesterol | TE | 0.0560 (− 0.2016, 0.3135) | 0.670 | ||
| CDE | 0.0436 (− 0.2102, 0.2973) | 0.736 | 77.9% | 0.147 | |
| INTref | − 0.0004 (− 0.0079, 0.0071) | 0.920 | − 0.7% | 0.920 | |
| INTmed | − 0.0003 (− 0.0200, 0.0195) | 0.979 | − 0.5% | 0.979 | |
| PIE | 0.0130 (− 0.0149, 0.0410) | 0.361 | 23.3% | 0.683 | |
| O_M | 22.8% | 0.670 | |||
| Parathormone | TE | 0.0337 (− 0.2019, 0.2693) | 0.779 | ||
| CDE | 0.0324 (− 0.2020, 0.2668) | 0.786 | 96.1% | 0.002 | |
| INTref | − 0.0020 (− 0.0186, 0.0147) | 0.815 | − 5.9% | 0.860 | |
| INTmed | 0.0026 (− 0.0055, 0.0107) | 0.532 | 7.7% | 0.790 | |
| PIE | 0.0007 (− 0.0043, 0.0056) | 0.783 | 2.1% | 0.837 | |
| O_M | 9.7% | 0.787 | |||
| TSH | TE | 0.0376 (− 0.1991, 0.2742) | 0.756 | ||
| CDE | 0.0342 (− 0.2051, 0.2735) | 0.779 | 91.1% | 0.012 | |
| INTref | 0.0004 (− 0.0066, 0.0075) | 0.904 | 1.2% | 0.922 | |
| INTmed | − 0.0006 (− 0.0041, 0.0030) | 0.761 | − 1.5% | 0.839 | |
| PIE | 0.0035 (− 0.0097, 0.0166) | 0.604 | 9.3% | 0.785 | |
| O_M | 7.8% | 0.779 | |||
| Prolactin | TE | 0.0369 (− 0.1988, 0.2727) | 0.759 | ||
| CDE | 0.0348 (− 0.1997, 0.2693) | 0.771 | 94.2% | < 0.001 | |
| INTref | 0.0012 (− 0.0114, 0.0138) | 0.854 | 3.2% | 0.869 | |
| INTmed | 0.0020 (− 0.0046, 0.0086) | 0.548 | 5.5% | 0.780 | |
| PIE | − 0.0011 (− 0.0062, 0.0041) | 0.685 | − 2.9% | 0.810 | |
| O_M | 2.6% | 0.799 | |||
| Estradiol | TE | 0.0434 (− 0.1963, 0.2831) | 0.722 | ||
| CDE | 0.0321 (− 0.2067, 0.2709) | 0.792 | 74.0% | 0.320 | |
| INTref | − 0.0004 (− 0.0043, 0.0035) | 0.837 | − 0.9% | 0.765 | |
| INTmed | 0.0005 (− 0.0077, 0.0086) | 0.910 | 1.1% | 0.899 | |
| PIE | 0.0112 (− 0.0062, 0.0287) | 0.208 | 25.9% | 0.731 | |
| O_M | 27.0% | 0.714 | |||
| Testosterone | TE | 0.0249 (− 0.2116, 0.2613) | 0.837 | ||
| CDE | 0.0251 (− 0.2073, 0.2576) | 0.832 | 101.1% | 0.008 | |
| INTref | 0.0006 (− 0.0187, 0.0200) | 0.948 | 2.6% | 0.947 | |
| INTmed | − 0.0001 (− 0.0043, 0.0040) | 0.948 | − 0.6% | 0.946 | |
| PIE | − 0.0008 (− 0.0058, 0.0043) | 0.765 | − 3.1% | 0.872 | |
| O_M | − 3.6% | 0.853 | |||
| SHBG | TE | 0.0810 (− 0.1913, 0.3533) | 0.560 | ||
| CDE | 0.0807 (− 0.1918, 0.3533) | 0.561 | 99.7% | < 0.001 | |
| INTref | 0.0001 (− 0.0097, 0.0099) | 0.986 | 0.1% | 0.986 | |
| INTmed | − 0.0006 (− 0.0053, 0.0040) | 0.784 | − 0.8% | 0.802 | |
| PIE | 0.0008 (− 0.0050, 0.0066) | 0.783 | 1.0% | 0.801 | |
| O_M | 0.2% | 0.879 | |||
| Progesterone | TE | 0.0326 (− 0.2022, 0.2674) | 0.785 | ||
| CDE | 0.0576 (− 0.1825, 0.2976) | 0.638 | 176.5% | 0.550 | |
| INTref | − 0.0271 (− 0.0789, 0.0247) | 0.305 | − 83.1% | 0.794 | |
| INTmed | − 0.0038 (− 0.0125, 0.0050) | 0.399 | − 11.5% | 0.795 | |
| PIE | 0.0059 (− 0.0061, 0.0179) | 0.335 | 18.1% | 0.794 | |
| O_M | 6.5% | 0.813 |
TE: total effect (total excess relative risk), CDE: excess relative risk due to controlled direct effect, INTref: excess relative risk due to reference interaction, INTmed: excess relative risk due to mediated interaction, PIE: excess relative risk due to pure indirect effect, O_M: overall mediated
CRP: C-reactive protein, HDL: High-density lipoprotein cholesterol, LDL: Light-density lipoprotein cholesterol, SHBG: Sex Hormone-Binding globulin, TSH: Thyroid-stimulating hormone, SHGB: Sex Hormone-binding globulin
Output of mediation analysis with causal effects estimated for a change in pollutant levels from the 25th to the 75th percentile
Adjusted for body mass index, menopausal hormone replacement therapy uses, urban/rural status at birth, urban/rural status at inclusion, alcohol drinking, breastfeeding, mammography before inclusion, oral contraceptive use, age at full-term pregnancy and parity, smoking status, total physical activity
Controlled direct effects are computed fixing the mediators at their median levels