Table 5.
Risk of endometrial cancer comparing the 5th to the 1st quintile for each estrogen metabolite: Subtype analyses according to tumor type (I vs. II) and grade (low- vs. high-grade).
| Type I | Type II | Low grade | High Grade | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (n=271) | (n=42) | (n=189) | (n=65) | |||||||||||
| Parent Estrogens | OR2 | (95% CI) | p-trend3 | OR2 | (95% CI) | p-trend3 | phet | OR2 | (95% CI) | p-trend3 | OR2 | (95% CI) | p-trend3 | phet |
| Estrone | 3.41 | (1.79–6.50) | <0.001 | 3.39 | (0.90–12.73) | 0.14 | 0.48 | 3.38 | (1.65–6.96) | <0.001 | 3.16 | (1.09–9.13) | 0.01 | 0.63 |
| Unconjugated Estrone | 2.91 | (1.58–5.37) | <0.001 | 1.50 | (0.46–4.87) | 0.69 | 0.07 | 2.65 | (1.34–5.21) | <0.001 | 2.51 | (0.89–7.08) | 0.11 | 0.27 |
| Conjugated Estrone | 3.04 | (1.62–5.70) | <0.001 | 4.22 | (1.02–17.54) | 0.15 | 0.60 | 3.00 | (1.49–6.06) | <0.001 | 2.67 | (0.98–7.29) | 0.03 | 0.68 |
| Estradiol | 1.70 | (0.89–3.25) | 0.13 | 0.76 | (0.22–2.62) | 0.67 | 0.29 | 1.48 | (0.72–3.04) | 0.16 | 1.89 | (0.54–6.62) | 0.98 | 0.35 |
| Unconjugated Estradiol | 6.97 | (3.20–15.20) | <0.001 | 1.80 | (0.43–7.49) | 0.83 | 0.01 | 8.92 | (3.38–23.54) | <0.001 | 3.27 | (1.03–10.36) | 0.09 | 0.14 |
| Conjugated Estradiol | 1.16 | (0.62–2.19) | 0.64 | 0.48 | (0.13–1.77) | 0.28 | 0.26 | 1.05 | (0.52–2.13) | 0.50 | 1.26 | (0.39–4.08) | 0.57 | 0.45 |
| 2-Hydroxylation Pathway | ||||||||||||||
| 2-Hydroxyestrone | 2.99 | (1.55–5.78) | <0.001 | 3.38 | (0.58–19.67) | 0.78 | 0.16 | 3.56 | (1.65–7.69) | 0.001 | 2.30 | (0.81–6.48) | 0.06 | 0.62 |
| 2-Hydroxyestradiol | 2.43 | (1.28–4.63) | 0.008 | 2.56 | (0.56–11.72) | 0.71 | 0.40 | 3.16 | (1.47–6.82) | 0.006 | 1.63 | (0.62–4.29) | 0.16 | 0.62 |
| 2-Methoxyestrone | 2.51 | (1.36–4.65) | <0.001 | 0.90 | (0.28–2.90) | 0.81 | 0.16 | 2.27 | (1.16–4.45) | 0.001 | 3.94 | (1.30–11.92) | 0.01 | 0.93 |
| Unconjugated 2-Methoxyestrone | 3.47 | (1.82–6.62) | <0.001 | 0.95 | (0.30–3.05) | 0.74 | 0.02 | 3.40 | (1.63–7.11) | 0.003 | 3.45 | (1.16–10.23) | 0.03 | 0.72 |
| Conjugated 2-Methoxyestrone | 1.71 | (0.95–3.08) | 0.007 | 1.19 | (0.37–3.84) | 0.53 | 0.67 | 1.62 | (0.85–3.09) | 0.01 | 1.99 | (0.77–5.13) | 0.07 | 0.97 |
| 2-Methoxyestradiol | 4.19 | (2.18–8.07) | <0.001 | 1.48 | (0.43–5.08) | 0.66 | 0.08 | 3.50 | (1.68–7.28) | <0.001 | 5.14 | (1.76–14.99) | 0.00 | 0.42 |
| Unconjugated 2-Methoxyestradiol | 3.85 | (1.99–7.45) | <0.001 | 1.68 | (0.52–5.43) | 0.55 | 0.20 | 3.43 | (1.63–7.25) | <0.001 | 4.07 | (1.33–12.45) | 0.01 | 0.76 |
| Conjugated 2-Methoxyestradiol | 3.79 | (1.97–7.29) | <0.001 | 1.97 | (0.52–7.41) | 0.51 | 0.15 | 3.35 | (1.61–6.94) | <0.001 | 4.03 | (1.38–11.78) | 0.01 | 0.87 |
| 2-Hydroxyestrone-3-methyl ether | 3.58 | (1.80–7.11) | 0.004 | 1.08 | (0.25–4.60) | 0.81 | 0.17 | 3.93 | (1.80–8.58) | 0.003 | 2.33 | (0.73–7.43) | 0.43 | 0.18 |
| 4-Hydroxylation Pathway | ||||||||||||||
| 4-Hydroxyestrone | 3.19 | (1.67–6.11) | <0.001 | 2.73 | (0.59–12.63) | 0.82 | 0.12 | 4.17 | (1.93–9.03) | <0.001 | 1.91 | (0.72–5.08) | 0.07 | 0.55 |
| 4-Methoxyestrone | 3.54 | (1.91–6.59) | <0.001 | 0.84 | (0.23–3.06) | 0.96 | 0.03 | 3.20 | (1.61–6.37) | <0.001 | 4.13 | (1.6–10.66) | 0.00 | 0.30 |
| 4-Methoxyestradiol | 4.00 | (2.06–7.79) | <0.001 | 2.23 | (0.59–8.45) | 0.44 | 0.12 | 3.70 | (1.75–7.83) | <0.001 | 3.60 | (1.31–9.90) | 0.00 | 0.80 |
| 16alpha-Hydroxylation Pathway | ||||||||||||||
| 16alpha-Hydroxyestrone | 2.84 | (1.49–5.41) | 0.001 | 2.23 | (0.47–10.61) | 0.91 | 0.14 | 3.10 | (1.48–6.50) | 0.002 | 2.50 | (0.90–6.96) | 0.05 | 0.83 |
| Estriol | 4.14 | (2.14–8.00) | <0.001 | 3.38 | (0.75–15.20) | 0.34 | 0.21 | 4.85 | (2.20–10.66) | <0.001 | 3.53 | (1.32–9.46) | 0.00 | 0.40 |
| Unconjugated Estriol | 3.34 | (1.75–6.35) | <0.001 | 1.83 | (0.43–7.84) | 0.88 | 0.03 | 3.02 | (1.47–6.19) | <0.001 | 4.05 | (1.39–11.77) | 0.01 | 0.84 |
| Conjugated Estriol | 3.35 | (1.73–6.45) | <0.001 | 4.60 | (0.85–25.08) | 0.40 | 0.38 | 3.69 | (1.71–7.96) | 0.003 | 3.23 | (1.17–8.93) | 0.01 | 0.54 |
| 16-Ketoestradiol | 3.23 | (1.67–6.27) | 0.002 | 3.27 | (0.74–14.51) | 0.52 | 0.32 | 3.59 | (1.65–7.79) | 0.004 | 2.65 | (0.95–7.40) | 0.03 | 0.90 |
| 16-Epiestriol | 3.33 | (1.70–6.54) | 0.001 | 1.35 | (0.32–5.66) | 0.99 | 0.11 | 4.43 | (1.96–9.98) | <0.001 | 2.21 | (0.76–6.46) | 0.19 | 0.29 |
| 17-Epiestriol | 2.57 | (1.36–4.85) | 0.005 | 1.60 | (0.40–6.39) | 0.60 | 0.40 | 3.62 | (1.66–7.92) | 0.006 | 1.33 | (0.53–3.35) | 0.17 | 0.53 |
1
Type I (66 adenocarcinomas, 194 endometrioid carcinomas, 11 mucinous) vs. Type II (34 serous, 6 clear cell, 2 other); grade of tumor (low = grade 1,2, high = grade 3, 4) evaluated among endometrioid carcinomas and adenocarcinomas only.
2
OR (quintile 5 vs. quintile 1) from model adjusted for matching factors [age at baseline, calendar year of blood draw, race/ethnicity, and recency of MHT use (never, ≤1/>1 year)] and education, BMI, cigarette smoking status, years of oral contracteptive use, age at menarche, gravidity, age at menopause, and previous tubal ligation.
3
p-values for trend across quintile (median value of category)