Table 4.
Associations of Risk Factors Among Serous Ovarian Carcinomas by Grade in the Ovarian Cancer Cohort Consortium
| Exposure | Grade, RR (95% CI) | P-het† | |||
|---|---|---|---|---|---|
| Well Differentiated* | Moderately Differentiated | Poorly Differentiated | Unknown | ||
| Parity | |||||
| Ever/never | 0.78 (0.47 to 1.29) | 0.77 (0.60 to 0.99) | 0.83 (0.72 to 0.96) | 0.88 (0.71 to 1.09) | .87 |
| No. of children, per one child | 0.89 (0.80 to 1.00) | 0.90 (0.85 to 0.95) | 0.94 (0.91 to 0.96) | 0.96 (0.93 to 1.01) | .20 |
| No. of children | |||||
| 0 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| 1 | 0.84 (0.41 to 1.73) | 0.90 (0.64 to 1.27) | 0.85 (0.69 to 1.05) | 0.94 (0.70 to 1.26) | |
| 2 | 0.88 (0.50 to 1.55) | 0.86 (0.65 to 1.13) | 0.89 (0.76 to 1.05) | 0.89 (0.70 to 1.13) | .42 |
| 3 | 0.88 (0.50 to 1.54) | 0.68 (0.51 to 0.91) | 0.87 (0.74 to 1.03) | 0.86 (0.67 to 1.10) | |
| ≥ 4 | 0.45 (0.22 to 0.91) | 0.68 (0.50 to 0.92) | 0.69 (0.58 to 0.82) | 0.89 (0.69 to 1.14) | |
| Oral contraceptive use | |||||
| Ever/never | 1.11 (0.72 to 1.72) | 0.80 (0.65 to 0.98) | 0.85 (0.76 to 0.95) | 0.77 (0.66 to 0.90) | .36 |
| Duration of use, per 5-year increase | 0.79 (0.62 to 1.00) | 0.82 (0.73 to 0.92) | 0.90 (0.84 to 0.96) | 0.77 (0.69 to 0.87) | .09 |
| Duration of use, years | |||||
| Never | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| ≤ 1 | 1.80 (0.98 to 3.30) | 0.90 (0.63 to 1.29) | 1.01 (0.84 to 1.20) | 0.96 (0.74 to 1.24) | |
| > 1-5 | 1.12 (0.65 to 1.94) | 0.95 (0.72 to 1.25) | 0.86 (0.74 to 1.00) | 0.85 (0.68 to 1.06) | .25 |
| > 5-10 | 0.94 (0.48 to 1.83) | 0.82 (0.60 to 1.13) | 0.77 (0.65 to 0.92) | 0.59 (0.44 to 0.79) | |
| > 10 | 0.56 (0.22 to 1.42) | 0.45 (0.28 to 0.73) | 0.76 (0.61 to 0.94) | 0.49 (0.34 to 0.71) | |
| Duration of breastfeeding, per 1 year‡ | 1.06 (0.68 to 1.66) | 0.93 (0.75 to 1.15) | 0.95 (0.83 to 1.08) | 0.89 (0.74 to 1.08) | .86 |
| Age at menarche | |||||
| Per 1-year increase | 1.01 (0.91 to 1.11) | 1.00 (0.94 to 1.06) | 1.01 (0.98 to 1.04) | 0.95 (0.91 to 1.00) | .21 |
| Age, years | |||||
| ≤ 11 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| 12 | 1.26 (0.70 to 2.28) | 0.86 (0.64 to 1.14) | 1.06 (0.91 to 1.23) | 0.86 (0.69 to 1.06) | |
| 13 | 1.37 (0.83 to 2.28) | 0.94 (0.73 to 1.20) | 1.10 (0.96 to 1.26) | 0.76 (0.62 to 0.92) | .22 |
| 14 | 1.20 (0.62 to 2.34) | 0.86 (0.62 to 1.18) | 1.16 (0.97 to 1.38) | 0.83 (0.65 to 1.05) | |
| ≥ 15 | 1.00 (0.49 to 2.05) | 0.99 (0.72 to 1.36) | 0.94 (0.78 to 1.14) | 0.80 (0.62 to 1.02) | |
| Age at menopause | |||||
| Per 5-year increase | 1.54 (1.23 to 1.91) | 1.04 (0.93 to 1.16) | 1.03 (0.97 to 1.10) | 1.05 (0.95 to 1.16) | .06 |
| Age, years | |||||
| ≤ 45 | 0.20 (0.07 to 0.56) | 0.92 (0.66 to 1.28) | 0.91 (0.77 to 1.09) | 0.89 (0.69 to 1.17) | |
| > 45-50 | 0.49 (0.29 to 0.84) | 1.21 (0.94 to 1.56) | 0.96 (0.83 to 1.10) | 0.98 (0.80 to 1.21) | .02 |
| > 50-55 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| > 55 | 0.41 (0.13 to 1.32) | 1.16 (0.73 to 1.84) | 0.97 (0.75 to 1.24) | 1.23 (0.87 to 1.73) | |
| Hormone therapy use§ | |||||
| Ever/never | 1.80 (1.15 to 2.83) | 1.57 (1.27 to 1.95) | 1.49 (1.33 to 1.67) | 1.23 (1.04 to 1.45) | .15 |
| Duration of use, per 5-year increase | 1.35 (1.18 to 1.53) | 1.26 (1.17 to 1.36) | 1.21 (1.16 to 1.26) | 1.20 (1.12 to 1.29) | .54 |
| Duration of use, years | |||||
| Never | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| ≤ 5 | 1.33 (0.71 to 2.48) | 1.26 (0.94 to 1.69) | 1.27 (1.09 to 1.48) | 1.12 (0.90 to 1.41) | .42 |
| > 5 | 2.91 (1.72 to 4.92) | 2.10 (1.60 to 2.76) | 1.80 (1.56 to 2.07) | 1.57 (1.27 to 1.95) | |
| Tubal ligation, ever/never | 1.25 (0.66 to 2.36) | 1.05 (0.71 to 1.57) | 0.92 (0.76 to 1.11) | 0.62 (0.43 to 0.88) | .10 |
| Hysterectomy, ever/never‖ | 0.87 (0.53 to 1.43) | 1.05 (0.84 to 1.33) | 1.01 (0.89 to 1.14) | 1.04 (0.87 to 1.25) | .90 |
| Endometriosis, yes/no | 3.77 (1.24 to 11.48) | 1.54 (0.72 to 3.30) | 1.11 (0.70 to 1.74) | 0.57 (0.18 to 1.80) | .12 |
| First-degree family history of breast cancer, yes/no | 1.23 (0.71 to 2.15) | 1.20 (0.91 to 1.58) | 1.12 (0.97 to 1.30) | 0.96 (0.76 to 1.21) | .58 |
| First-degree family history of ovarian cancer, yes/no | 0.90 (0.22 to 3.70) | 1.46 (0.83 to 2.54) | 1.63 (1.25 to 2.13) | 1.64 (1.08 to 2.47) | .82 |
| Body mass index | |||||
| Per 5 kg/m2 | 0.92 (0.74 to 1.14) | 0.99 (0.90 to 1.08) | 0.92 (0.87 to 0.97) | 1.05 (0.97 to 1.13) | .03 |
| Categorical, kg/m2 | |||||
| < 20 | 1.33 (0.67 to 2.62) | 0.78 (0.51 to 1.19) | 1.15 (0.95 to 1.39) | 1.11 (0.83 to 1.49) | |
| 20 to < 25 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| 25 to < 30 | 1.02 (0.65 to 1.59) | 1.08 (0.88 to 1.33) | 0.84 (0.74 to 0.94) | 0.89 (0.75 to 1.05) | .22 |
| 30 to < 35 | 0.85 (0.44 to 1.66) | 0.98 (0.73 to 1.32) | 0.85 (0.72 to 1.00) | 1.04 (0.83 to 1.32) | |
| ≥ 35 | 1.15 (0.51 to 2.59) | 0.88 (0.56 to 1.39) | 0.88 (0.70 to 1.10) | 1.25 (0.92 to 1.70) | |
| Height | |||||
| Per 0.5 m | 1.05 (0.93 to 1.18) | 1.06 (0.99 to 1.14) | 1.07 (1.03 to 1.11) | 1.03 (0.97 to 1.08) | .72 |
| Categorical, m | |||||
| < 1.60 | 0.83 (0.49 to 1.39) | 0.92 (0.72 to 1.17) | 0.82 (0.72 to 0.95) | 1.00 (0.82 to 1.21) | |
| 1.60 to < 1.65 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | .70 |
| 1.65 to < 1.70 | 1.21 (0.75 to 1.95) | 1.03 (0.81 to 1.30) | 1.03 (0.91 to 1.18) | 1.15 (0.95 to 1.39) | |
| ≥ 1.70 | 0.96 (0.55 to 1.69) | 1.08 (0.83 to 1.41) | 1.06 (0.92 to 1.22) | 0.96 (0.77 to 1.20) | |
| Smoking | |||||
| Ever/never | 1.10 (0.85 to 1.41) | 0.95 (0.84 to 1.07) | 0.96 (0.90 to 1.03) | 1.04 (0.95 to 1.15) | .38 |
| Continuous pack-years, per 20 pack-years | 0.87 (0.59 to 1.26) | 1.00 (0.87 to 1.15) | 0.98 (0.92 to 1.05) | 1.07 (0.97 to 1.18) | .44 |
| Categorical, pack-years | |||||
| Never | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| ≤ 20 | 1.20 (0.70 to 2.08) | 1.00 (0.76 to 1.32) | 1.08 (0.94 to 1.24) | 1.10 (0.88 to 1.36) | .91 |
| > 20 | 0.72 (0.34 to 1.52) | 0.97 (0.71 to 1.31) | 1.03 (0.89 to 1.21) | 1.09 (0.87 to 1.38) | |
NOTE. Associations stratified by birth year and cohort and adjusted for age at study entry, parity, and duration of oral contraceptive use (except when parity or oral contraceptive use was the primary exposure of interest, and then we adjusted only for the other risk factor) by using pooled analyses of all cohorts combined. Five cohorts with no information on grade for any ovarian cancer cases were excluded. Abbreviation: P-het, P value for heterogeneity; RR, relative risk.
*
Number of cases ranged from 28 (breastfeeding) to 121 (oral contraceptive use) for well-differentiated, 113 (endometriosis) to 496 (oral contraceptive use) for moderately differentiated, 338 (breastfeeding) to 1,637 (oral contraceptive use) for poorly differentiated, and 141 (endometriosis) to 773 (oral contraceptive use) for unknown grade.
†
Assessed by using a likelihood ratio test that compared a Cox proportional hazards competing-risks model to allow for the association to vary by grade to a model that forced the association to be the same across grades.
‡
Parous women only.
§
Postmenopausal women only.
‖
Also adjusted for duration of hormone therapy use.