TABLE 6.
Association between dietary ω-3 PUFA intake and endometrial cancer, defined by histopathologic subtype (n = 87,360)1
| Energy-adjusted quintiles of fatty acid intake |
||||||
| 1 | 2 | 3 | 4 | 5 | P-trend | |
| ω-3 Fatty acids | ||||||
| EPA + DPA + DHA, mg/d | ≤56.8 | 56.9–91.2 | 91.3–133.9 | 134.0–205.2 | >205.2 | |
| Type I, n cases | 226 | 207 | 220 | 190 | 189 | |
| HR (95% CI) | 1.00 (reference) | 1.01 (0.81, 1.25) | 0.99 (0.79, 1.23) | 0.80 (0.64, 1.01) | 0.77 (0.61, 0.98) | 0.006 |
| Type II, n cases | 31 | 25 | 40 | 44 | 40 | |
| HR (95% CI) | 1.00 (reference) | 0.86 (0.46, 1.60) | 1.26 (0.71, 2.23) | 1.68 (0.98, 2.89) | 1.15 (0.64, 2.07) | 0.146 |
| P-difference | 0.001 | |||||
| EPA (20:5ω-3), mg/d | ≤15.6 | 15.7–27.4 | 27.5–41.3 | 41.4–63.6 | >63.6 | |
| Type I, n cases | 224 | 215 | 197 | 215 | 181 | |
| HR (95% CI) | 1.00 (reference) | 1.09 (0.87, 1.35) | 0.90 (0.72, 1.13) | 0.91 (0.72, 1.14) | 0.75 (0.59, 0.95) | 0.006 |
| Type II, n cases | 28 | 30 | 40 | 44 | 38 | |
| HR (95% CI) | 1.00 (reference) | 1.10 (0.59, 2.05) | 1.44 (0.80, 2.57) | 1.78 (1.01, 3.13) | 1.30 (0.71, 2.37) | 0.139 |
| P-difference | 0.002 | |||||
| DPA (22:5ω-3), mg/d | ≤6.8 | 6.9–10.7 | 10.8–15.2 | 15.3–22.2 | >22.2 | |
| Type I, n cases | 235 | 206 | 208 | 197 | 186 | |
| HR (95% CI) | 1.00 (reference) | 0.99 (0.79, 1.23) | 0.92 (0.74, 1.15) | 0.74 (0.59, 0.93) | 0.77 (0.61, 0.97) | 0.002 |
| Type II, n cases | 27 | 34 | 36 | 35 | 48 | |
| HR (95% CI) | 1.00 (reference) | 1.17 (0.64, 2.14) | 1.35 (0.75, 2.43) | 1.35 (0.75, 2.43) | 1.63 (0.92, 2.87) | 0.083 |
| P-difference | <0.001 | |||||
| DHA (22:6ω-3), mg/d | ≤32.8 | 32.9–51.9 | 52.0–76.8 | 76.9–121.0 | >121.0 | |
| Type I, n cases | 240 | 198 | 216 | 188 | 190 | |
| HR (95% CI) | 1.00 (reference) | 0.92 (0.74, 1.14) | 0.92 (0.74, 1.15) | 0.73 (0.58, 0.92) | 0.73 (0.58, 0.92) | 0.001 |
| Type II, n cases | 32 | 26 | 40 | 41 | 41 | |
| HR (95% CI) | 1.00 (reference) | 0.77 (0.41, 1.45) | 1.33 (0.77, 2.31) | 1.48 (0.86, 2.55) | 1.08 (0.60, 1.93) | 0.240 |
| P-difference | 0.002 | |||||
| ALA (18:3ω-3), mg/d | ≤921.6 | 921.7–1130.6 | 1130.7–1333.1 | 1333.2–1640.0 | >1640.0 | |
| Type I, n cases | 227 | 207 | 184 | 194 | 220 | |
| HR (95% CI) | 1.00 (reference) | 0.99 (0.80, 1.23) | 0.80 (0.63, 1.02) | 0.98 (0.79, 1.23) | 0.98 (0.79, 1.23) | 0.871 |
| Type II, n cases | 42 | 32 | 33 | 41 | 32 | |
| HR (95% CI) | 1.00 (reference) | 0.89 (0.50, 1.57) | 1.14 (0.66, 1.97) | 1.33 (0.78, 2.25) | 0.91 (0.51, 1.61) | 0.709 |
| P-difference | 0.545 | |||||
| ω-6 Fatty acids | ||||||
| LA + AA, mg/d | ≤8328.5 | 8328.6–10,061.7 | 10,061.8–11,539.7 | 11,539.8–13,494.5 | >13,494.5 | |
| Type I, n cases | 216 | 192 | 195 | 194 | 235 | |
| HR (95% CI) | 1.00 (reference) | 0.80 (0.64, 1.01) | 0.93 (0.74, 1.17) | 0.92 (0.73, 1.16) | 1.15 (0.92, 1.43) | 0.118 |
| Type II, n cases | 40 | 36 | 30 | 40 | 34 | |
| HR (95% CI) | 1.00 (reference) | 1.00 (0.59, 1.68) | 0.77 (0.43, 1.37) | 1.14 (0.67, 1.95) | 0.83 (0.46, 1.47) | 0.731 |
| P-difference | 0.532 | |||||
| LA (18:2ω-6), mg/d | ≤8235.9 | 8236.0–9962.1 | 9962.2–11,438.1 | 11,438.2–13,391.3 | >13,391.3 | |
| Type I, n cases | 215 | 193 | 196 | 194 | 234 | |
| HR (95% CI) | 1.00 (reference) | 0.78 (0.62, 0.98) | 0.92 (0.73, 1.16) | 0.91 (0.72, 1.15) | 1.13 (0.90, 1.40) | 0.147 |
| Type II, n cases | 41 | 35 | 30 | 40 | 34 | |
| HR (95% CI) | 1.00 (reference) | 1.00 (0.59, 1.68) | 0.77 (0.44, 1.37) | 1.14 (0.67, 1.95) | 0.83 (0.46, 1.47) | 0.733 |
| P-difference | 0.579 | |||||
| AA (20:4ω-6), mg/d | ≤61.5 | 61.6–80.9 | 81.0–99.8 | 99.9–127.5 | >127.5 | |
| Type I, n cases | 256 | 189 | 192 | 186 | 209 | |
| HR (95% CI) | 1.00 (reference) | 0.75 (0.60, 0.93) | 0.78 (0.63, 0.97) | 0.68 (0.55, 0.86) | 0.74 (0.59, 0.92) | 0.004 |
| Type II, n cases | 34 | 43 | 31 | 31 | 41 | |
| HR (95% CI) | 1.00 (reference) | 1.34 (0.79, 2.28) | 0.90 (0.51, 1.61) | 1.04 (0.59, 1.82) | 1.01 (0.58, 1.77) | 0.667 |
| P-difference | 0.317 | |||||
| ω-3:ω-6 | ||||||
| Ratio of EPA + DPA + DHA to LA + AA, mg/d | ≤0.005 | 0.006–0.008 | 0.009–0.013 | 0.014–0.021 | >0.021 | |
| Type I, n cases | 233 | 214 | 187 | 212 | 186 | |
| HR (95% CI) | 1.00 (reference) | 0.97 (0.78, 1.20) | 0.80 (0.64, 1.01) | 0.86 (0.69, 1.08) | 0.73 (0.58, 0.92) | 0.006 |
| Type II, n cases | 27 | 27 | 45 | 39 | 42 | |
| HR (95% CI) | 1.00 (reference) | 1.12 (0.58, 2.13) | 1.97 (1.10, 3.53) | 1.65 (0.90, 3.01) | 1.61 (0.88, 2.96) | 0.069 |
| P-difference | <0.001 | |||||
Type I cancers were predominantly carcinomas and endometrioid adenocarcinomas (n = 1032). Type II cancers included serous, papillary, or clear cell carcinomas and mixed tumors (i.e., carcinosarcomas) (n = 180). Regression models for type I cancers censor type II tumors and other subtypes (n = 41), and models for type II tumors censor type I and other subtypes at their respective times at diagnosis. HRs (95% CI) were derived from Cox proportional hazards regression models adjusted for age (time variable), clinical trial/observational study intervention assignment, US region, race, education, BMI, smoking, alcohol, physical activity, age at menarche, age at first birth, age at menopause, parity, duration of combined menopausal hormone therapy, duration of estrogen-alone hormone therapy, duration of oral contraceptive use, oophoerectomy status, family history of endometrial cancer, history of diabetes, and total energy. P-trend values were calculated by treating categorical exposure variables as continuous in regression models. P values for the difference in associations between fatty acids and endometrial cancer subtypes were compared by using a case-only–adjusted logistic regression model. AA, arachidonic acid; ALA, α-linolenic acid; DPA, docosapentaenoic acid; LA, linoleic acid.