Table 4.
Multivariable hazard ratios (HR) and 95 % confidence intervals (CIs) for risk of endometrial cancer by tertiles of 2-pathway and 4-pathway metabolites
| Estrogen/EM | Cases (n = 66) | Subcohort (n = 346) | HR (95 % CI)a | HR (95 % CI)b | HR (95 % CI)c |
|---|---|---|---|---|---|
| 2-Pathway metabolites | |||||
| 2-Catechols | |||||
| T1 | 8 | 115 | 1.00 | 1.00 | 1.00 |
| T2 | 23 | 113 | 2.30 (0.96, 5.52) | 2.24 (0.85, 5.95) | 1.93 (0.78, 4.78) |
| T3 | 35 | 118 | 3.20 (1.36, 7.51) | 2.86 (1.10, 7.39) | 1.88 (0.75, 4.73) |
| p trend | 0.008 | 0.03 | 0.25 | ||
| 2-Hydroxyestrone | |||||
| T1 | 8 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 21 | 114 | 1.97 (0.80, 4.86) | 2.01 (0.74, 5.45) | 1.63 (0.64, 4.17) |
| T3 | 37 | 118 | 3.24 (1.38, 7.59) | 2.77 (1.08, 7.12) | 1.97 (0.78, 4.94) |
| p trend | 0.005 | 0.03 | 0.16 | ||
| 2-Hydroxyestradiol | |||||
| T1 | 15 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 19 | 115 | 1.11 (0.53, 2.32) | 1.00 (0.42, 2.38) | 1.02 (0.48, 2.18) |
| T3 | 32 | 117 | 1.51 (0.74, 3.09) | 1.30 (0.60, 2.82) | 0.88 (0.40, 1.93) |
| p trend | 0.25 | 0.48 | 0.72 | ||
| 2-Methylated catechols | |||||
| T1 | 19 | 115 | 1.00 | 1.00 | 1.00 |
| T2 | 23 | 114 | 1.14 (0.57, 2.29) | 0.95 (0.46, 1.96) | 1.06 (0.52, 2.15) |
| T3 | 24 | 117 | 1.25 (0.63, 2.47) | 1.09 (0.54, 2.18) | 0.69 (0.32, 1.49) |
| p trend | 0.52 | 0.82 | 0.34 | ||
| 2-Methoxyestrone | |||||
| T1 | 17 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 20 | 114 | 1.08 (0.53, 2.23) | 0.94 (0.45, 1.95) | 0.99 (0.47, 2.06) |
| T3 | 29 | 118 | 1.45 (0.72, 2.91) | 1.26 (0.61, 2.58) | 0.78 (0.35, 1.74) |
| p trend | 0.29 | 0.52 | 0.52 | ||
| 2-Methoxyestradiol | |||||
| T1 | 22 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 29 | 115 | 1.06 (0.56, 2.01) | 1.01 (0.50, 2.04) | 0.98 (0.51, 1.90) |
| T3 | 15 | 117 | 0.68 (0.33, 1.40) | 0.64 (0.30, 1.39) | 0.45 (0.21, 0.98) |
| p trend | 0.30 | 0.26 | 0.04 | ||
| 3-Methoxyestrone | |||||
| T1 | 22 | 115 | 1.00 | 1.00 | 1.00 |
| T2 | 25 | 114 | 1.50 (0.77, 2.94) | 1.24 (0.60, 2.54) | 1.22 (0.61, 2.42) |
| T3 | 19 | 117 | 0.95 (0.47, 1.88) | 0.83 (0.40, 1.70) | 0.53 (0.24, 1.18) |
| p trend | 0.91 | 0.64 | 0.11 | ||
| 4-Pathway metabolites | |||||
| 4-Hydroxyestrone | |||||
| T1 | 9 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 20 | 114 | 1.88 (0.80, 4.39) | 1.79 (0.70, 4.63) | 1.56 (0.64, 3.78) |
| T3 | 37 | 118 | 2.83 (1.26, 6.36) | 2.53 (1.04, 6.16) | 1.70 (0.71, 4.04) |
| p trend | 0.01 | 0.04 | 0.27 | ||
| 4-Methylated catechols | |||||
| T1 | 23 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 26 | 115 | 1.12 (0.59, 2.12) | 0.93 (0.48, 1.80) | 0.89 (0.46, 1.72) |
| T3 | 17 | 117 | 0.80 (0.39, 1.65) | 0.66 (0.31, 1.38) | 0.48 (0.20, 1.00) |
| p trend | 0.56 | 0.29 | 0.04 | ||
| 4-Methoxyestrone | |||||
| T1 | 20 | 115 | 1.00 | 1.00 | 1.00 |
| T2 | 26 | 114 | 1.24 (0.64, 2.40) | 1.03 (0.51, 2.08) | 1.03 (0.52, 2.04) |
| T3 | 20 | 117 | 1.04 (0.49, 2.19) | 0.80 (0.38, 1.74) | 0.58 (0.27, 1.29) |
| p trend | 0.92 | 0.62 | 0.16 | ||
| 4-Methoxyestradiol | |||||
| T1 | 23 | 114 | 1.00 | 1.00 | 1.00 |
| T2 | 30 | 114 | 1.39 (0.72, 2.68) | 1.20 (0.61, 2.37) | 1.29 (0.65, 2.54) |
| T3 | 13 | 118 | 0.65 (0.30, 1.43) | 0.58 (0.26, 1.30) | 0.38 (0.16, 0.94) |
| p trend | 0.33 | 0.20 | 0.03 | ||
The following tertile categories (T1, T2, T3 pmol/L) determined based on the distribution of each estrogen or estrogen metabolite among the subcohort: 2-catechols (<61.22, 61.22–86.84, >86.84), 2-hydroxyestrone (<50.57, 50.57–72.98, >72.98), 2-hydroxyestradiol (<10.8, 10.8–14.33, >14.33), 2-methylated catechols (<34.86, 34.86–53.70, >53.70), 2-methoxyestrone (<20.41, 20.41–34.34, >34.34), 2-methoxyestradiol (<9.90, 9.90–14.92, >14.92), 3-methoxyestrone (<3.53, 3.53–4.96, >4.96), 4-hydroxyestrone (<8.23, 8.23–12.13, >12.13), 4-methylated catechols (<5.35, 5.35–7.74, >7.74), 4-methoxyestrone (<3.42, 3.42–4.50, >4.50), 4-methoxyestradiol (<2.08, 2.08–3.41, >3.41)
aAdjusted for clinic and trial participation status
bAdjusted for clinic, trial participation status, and body mass index
cAdjusted for clinic, trial participation status, and estradiol