Table 5.
Four-way decomposition of each mediator of the associations between PCB153 and breast cancer risk
| Mediation | Effect | Estimate (CI 95%) | P value | Proportion | P value |
|---|---|---|---|---|---|
| Albumin | TE | 0.4563 (− 0.0831, 0.9957) | 0.097 | ||
| CDE | 0.4369 (− 0.1007, 0.9746) | 0.111 | 95.7% | < 0.001 | |
| INTref | 0.0204 (− 0.0320, 0.0728) | 0.445 | 4.5% | 0.475 | |
| INTmed | − 0.0139 (− 0.0443, 0.0164) | 0.368 | − 3.1% | 0.413 | |
| PIE | 0.0129 (− 0.0119, 0.0377) | 0.306 | 2.8% | 0.375 | |
| O_M | − 0.2% | 0.946 | |||
| CRP | TE | 0.4211 (− 0.1049, 0.9471) | 0.117 | ||
| CDE | 0.4462 (− 0.0882, 0.9806) | 0.102 | 106.0% | < 0.001 | |
| INTref | − 0.0251 (− 0.0821, 0.0319) | 0.388 | − 6.0% | 0.435 | |
| INTmed | − 0.0021 (− 0.0131, 0.0090) | 0.711 | − 0.5% | 0.715 | |
| PIE | 0.0021 (− 0.0088, 0.0130) | 0.705 | 0.5% | 0.714 | |
| O_M | 0.0% | 0.994 | |||
| Triglycerides | TE | 0.4763 (− 0.0883, 1.0410) | 0.098 | ||
| CDE | 0.4948 (− 0.0772, 1.0667) | 0.090 | 103.9% | < 0.001 | |
| INTref | − 0.0184 (− 0.0507, 0.0139) | 0.265 | − 3.9% | 0.305 | |
| INTmed | − 0.0001 (− 0.0151, 0.0150) | 0.997 | 0.0% | 0.997 | |
| PIE | 0.0001 (− 0.0018, 0.0018) | 0.997 | 0.0% | 0.997 | |
| O_M | 0.0% | 0.997 | |||
| Cholesterol | TE | 0.5117 (− 0.0634, 1.0868) | 0.081 | ||
| CDE | 0.5158 (− 0.0611, 1.0928) | 0.080 | 100.8% | < 0.001 | |
| INTref | − 0.0017 (− 0.0232, 0.0197) | 0.875 | − 0.3% | 0.875 | |
| INTmed | − 0.0027 (− 0.0184, 0.0129) | 0.730 | − 0.5% | 0.732 | |
| PIE | 0.0003 (− 0.0039, 0.0046) | 0.873 | 0.1% | 0.873 | |
| O_M | − 0.5% | 0.739 | |||
| HDL cholesterol | TE | 0.5204 (− 0.0624, 1.1032) | 0.080 | ||
| CDE | 0.5379 (− 0.0546, 1.1303) | 0.075 | 103.4% | < 0.001 | |
| INTref | − 0.0118 (− 0.0427, 0.0191) | 0.455 | − 2.3% | 0.455 | |
| INTmed | − 0.0066 (− 0.0268, 0.0136) | 0.523 | − 1.3% | 0.526 | |
| PIE | 0.0009 (− 0.0128, 0.0147) | 0.894 | 0.2% | 0.894 | |
| O_M | − 1.1% | 0.624 | |||
| LDL cholesterol | TE | 0.5723 (− 0.0436, 1.1882) | 0.069 | ||
| CDE | 0.5481 (− 0.0487, 1.1449) | 0.072 | 95.8% | < 0.001 | |
| INTref | 0.0121 (− 0.0355, 0.0597) | 0.618 | 2.1% | 0.604 | |
| INTmed | 0.0079 (− 0.0177, 0.0335) | 0.545 | 1.4% | 0.525 | |
| PIE | 0.0042 (− 0.0117, 0.0200) | 0.605 | 0.7% | 0.611 | |
| O_M | 2.1% | 0.497 | |||
| Parathormone | TE | 0.3785 (− 0.1522, 0.9092) | 0.162 | ||
| CDE | 0.3702 (− 0.1577, 0.8982) | 0.169 | 97.8% | < 0.001 | |
| INTref | − 0.0073 (− 0.0255, 0.0109) | 0.430 | − 1.9% | 0.456 | |
| INTmed | 0.0109 (− 0.0123, 0.0341) | 0.357 | 2.9% | 0.393 | |
| PIE | 0.0047 (− 0.0144, 0.0237) | 0.631 | 1.2% | 0.638 | |
| O_M | 4.1% | 0.332 | |||
| TSH | TE | 0.3490 (− 0.1430, 0.8410) | 0.164 | ||
| CDE | 0.3608 (− 0.1374, 0.8591) | 0.156 | 103.4% | < 0.001 | |
| INTref | − 0.0071 (− 0.0309, 0.0167) | 0.559 | − 2.0% | 0.565 | |
| INTmed | 0.0027 (− 0.0091, 0.0145) | 0.654 | 0.8% | 0.689 | |
| PIE | − 0.0075 (− 0.0354, 0.0205) | 0.600 | − 2.1% | 0.631 | |
| O_M | − 1.4% | 0.631 | |||
| Prolactin | TE | 0.4295 (− 0.0944, 0.9534) | 0.108 | ||
| CDE | 0.4299 (− 0.0946, 0.9543) | 0.108 | 100.1% | < 0.001 | |
| INTref | 0.0003 (− 0.0051, 0.0058) | 0.905 | 0.1% | 0.905 | |
| INTmed | − 0.0022 (− 0.0181, 0.0136) | 0.782 | − 0.5% | 0.784 | |
| PIE | 0.0015 (− 0.0133, 0.0163) | 0.841 | 0.4% | 0.842 | |
| O_M | − 0.2% | 0.940 | |||
| Estradiol | TE | 0.3752 (− 0.1330, 0.8835) | 0.148 | ||
| CDE | 0.3570 (− 0.1500, 0.8641) | 0.168 | 95.2% | < 0.001 | |
| INTref | − 0.0060 (− 0.0195, 0.0074) | 0.381 | − 1.6% | 0.248 | |
| INTmed | 0.0079 (− 0.0160, 0.0318) | 0.517 | 2.1% | 0.474 | |
| PIE | 0.0163 (− 0.0102, 0.0427) | 0.227 | 4.3% | 0.345 | |
| O_M | 6.4% | 0.266 | |||
| Testosterone | TE | 0.3552 (− 0.1657, 0.8762) | 0.181 | ||
| CDE | 0.3759 (− 0.1457, 0.8975) | 0.158 | 105.8% | < 0.001 | |
| INTref | − 0.0175 (− 0.0597, 0.0247) | 0.416 | − 4.9% | 0.502 | |
| INTmed | − 0.0075 (− 0.0344, 0.0194) | 0.584 | − 2.1% | 0.601 | |
| PIE | 0.0044 (− 0.0118, 0.0206) | 0.595 | 1.2% | 0.624 | |
| O_M | − 0.9% | 0.649 | |||
| SHBG | TE | 0.5035 (− 0.0961, 1.1030) | 0.100 | ||
| CDE | 0.5021 (− 0.0975, 1.1016) | 0.101 | 99.7% | < 0.001 | |
| INTref | 0.0015 (− 0.0180, 0.0211) | 0.878 | 0.3% | 0.879 | |
| INTmed | − 0.0034 (− 0.0168, 0.0101) | 0.624 | − 0.7% | 0.636 | |
| PIE | 0.0032 (− 0.0089, 0.0154) | 0.600 | 0.6% | 0.614 | |
| O_M | 0.0% | 0.979 | |||
| Progesterone | TE | 0.4212 (− 0.0995, 0.9420) | 0.113 | ||
| CDE | 0.4321 (− 0.0897, 0.9539) | 0.105 | 102.6% | < 0.001 | |
| INTref | − 0.0138 (− 0.0936, 0.0661) | 0.735 | − 3.3% | 0.744 | |
| INTmed | − 0.0015 (− 0.0115, 0.0086) | 0.772 | − 0.4% | 0.778 | |
| PIE | 0.0044 (− 0.0095, 0.0183) | 0.537 | 1.0% | 0.561 | |
| O_M | 0.7% | 0.646 |
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