TABLE 3.
Association between dietary ω-3 PUFA intake and endometrial cancer risk in the WHI Observational Study and Clinical Trials (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 | |
| Cases, n | 267 | 238 | 271 | 241 | 236 | |
| HR (95% CI)2 | 1.00 (reference) | 0.96 (0.81, 1.15) | 1.09 (0.92, 1.30) | 0.95 (0.80, 1.14) | 0.92 (0.77, 1.09) | 0.353 |
| HR (95% CI)3 | 1.00 (reference) | 0.98 (0.80, 1.20) | 1.03 (0.84, 1.26) | 0.90 (0.73, 1.11) | 0.81 (0.66, 1.00) | 0.040 |
| EPA (20:5ω-3), mg/d | ≤15.6 | 15.7–27.4 | 27.5–41.3 | 41.4–63.6 | >63.6 | |
| Cases, n | 262 | 253 | 244 | 266 | 228 | |
| HR (95% CI)2 | 1.00 (reference) | 1.05 (0.88, 1.25) | 1.00 (0.84, 1.20) | 1.08 (0.91, 1.28) | 0.91 (0.76, 1.08) | 0.427 |
| HR (95% CI)3 | 1.00 (reference) | 1.09 (0.89, 1.33) | 0.96 (0.78, 1.18) | 1.00 (0.81, 1.22) | 0.81 (0.65, 1.01) | 0.043 |
| DPA (22:5ω-3), mg/d | ≤6.8 | 6.9–10.7 | 10.8–15.2 | 15.3–22.2 | >22.2 | |
| Cases, n | 271 | 252 | 248 | 242 | 240 | |
| HR (95% CI)2 | 1.00 (reference) | 1.00 (0.84, 1.19) | 0.98 (0.82, 1.17) | 0.94 (0.79, 1.12) | 0.92 (0.77, 1.09) | 0.239 |
| HR (95% CI)3 | 1.00 (reference) | 1.03 (0.84, 1.26) | 0.95 (0.78, 1.17) | 0.81 (0.66, 1.00) | 0.85 (0.69, 1.05) | 0.019 |
| DHA (22:6ω-3), mg/d | ≤32.8 | 32.9–51.9 | 52.0–76.8 | 76.9–121.0 | >121.0 | |
| Cases, n | 283 | 232 | 263 | 236 | 239 | |
| HR (95% CI)2 | 1.00 (reference) | 0.89 (0.74, 1.06) | 1.00 (0.84, 1.19) | 0.88 (0.74, 1.05) | 0.87 (0.74, 1.04) | 0.157 |
| HR (95% CI)3 | 1.00 (reference) | 0.91 (0.74, 1.11) | 0.97 (0.79, 1.18) | 0.81 (0.66, 1.00) | 0.77 (0.63, 0.95) | 0.010 |
| ALA (18:3ω-3), mg/d | ≤921.6 | 921.7–1130.6 | 1130.7–1333.1 | 1333.2–1640.0 | >1640.0 | |
| Cases, n | 285 | 244 | 221 | 241 | 236 | |
| HR (95% CI)2 | 1.00 (reference) | 0.93 (0.78, 1.11) | 0.85 (0.71, 1.02) | 0.92 (0.77, 1.09) | 0.96 (0.81, 1.13) | 0.604 |
| HR (95% CI)3 | 1.00 (reference) | 0.94 (0.77, 1.15) | 0.83 (0.67, 1.02) | 0.98 (0.80, 1.21) | 0.96 (0.79, 1.18) | 0.900 |
| 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 | |
| Cases, n | 270 | 234 | 229 | 242 | 278 | |
| HR (95% CI)2 | 1.00 (reference) | 0.93 (0.78, 1.12) | 0.93 (0.78, 1.12) | 0.98 (0.82, 1.18) | 1.08 (0.91, 1.27) | 0.296 |
| HR (95% CI)3 | 1.00 (reference) | 0.81 (0.66, 1.00) | 0.88 (0.72, 1.09) | 0.94 (0.76, 1.17) | 1.09 (0.89, 1.34) | 0.180 |
| 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 | |
| Cases, n | 270 | 234 | 230 | 242 | 277 | |
| HR (95% CI)2 | 1.00 (reference) | 0.93 (0.78, 1.12) | 0.94 (0.78, 1.12) | 0.99 (0.83, 1.18) | 1.07 (0.91, 1.27) | 0.315 |
| HR (95% CI)3 | 1.00 (reference) | 0.79 (0.64, 0.98) | 0.88 (0.71, 1.08) | 0.93 (0.76, 1.15) | 1.08 (0.88, 1.32) | 0.216 |
| AA (20:4ω-6), mg/d | ≤61.5 | 61.6–80.9 | 81.0–99.8 | 99.9–127.5 | >127.5 | |
| Cases, n | 304 | 238 | 229 | 225 | 257 | |
| HR (95% CI)2 | 1.00 (reference) | 0.84 (0.70, 0.99) | 0.81 (0.68, 0.97) | 0.80 (0.67, 0.95) | 0.90 (0.76, 1.06) | 0.163 |
| HR (95% CI)3 | 1.00 (reference) | 0.78 (0.64, 0.95) | 0.77 (0.63, 0.94) | 0.71 (0.58, 0.87) | 0.75 (0.61, 0.91) | 0.002 |
| 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 | |
| Cases, n | 269 | 248 | 241 | 259 | 236 | |
| HR (95% CI)2 | 1.00 (reference) | 1.01 (0.84, 1.20) | 0.97 (0.81, 1.15) | 1.02 (0.85, 1.21) | 0.90 (0.75, 1.07) | 0.292 |
| HR (95% CI)3 | 1.00 (reference) | 0.99 (0.80, 1.21) | 0.92 (0.75, 1.13) | 0.94 (0.76, 1.15) | 0.81 (0.65, 1.00) | 0.053 |
P-trend values were calculated by treating categorical exposure variables as continuous in regression models. AA, arachidonic acid; ALA, α-linolenic acid; DPA, docosapentaenoic acid; LA, linoleic acid; WHI, Women’s Health Initiative.
Derived from Cox proportional hazards regression models adjusted for age (time variable) and total energy.
Further adjusted for 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, and history of diabetes.