Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies

Abstract

Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships.

Methods and findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p=0.02) in ever-users of hormone therapy.

Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors' Summary.

Figure 1. Relative risk of ovarian cancer in relation to height and body mass index by study.

Relative risk¹ (RR¹) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy. Relative risk² (RR²) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, height, duration of oral contraceptive use, and ever use of hormone therapy. SE, standard error.

Figure 2. Relative risk of ovarian cancer in relation to height and BMI in various subgroups of women.

Relative risk¹ (RR¹) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy (HT). Relative risk² (RR²) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, height, duration of oral contraceptive use, and ever use of hormone therapy. ^† numbers do not always add to the total because of missing values; ^‡ never-user of hormone therapy. Case–control studies with hospital controls are excluded. The dotted line represents the overall result for all women. SE, standard error.

Figure 3. Relative risk of ovarian cancer by height.

Relative risk compared to women with height <160 cm and stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy. Relative risk estimates are plotted against the mean height in each category (<160, 160–164, 165–169, and 170+ cm). Case–control studies with hospital controls are excluded.

Figure 4. Relative risk of ovarian cancer by body mass index.

Relative risk in (A) never-users of hormone therapy (HT) and (B) ever-users of hormone therapy, taking women with a body mass index of <25 kg/m² in each group as the baseline (relative risk = 1.0), and stratified by study, age at diagnosis, parity, height, and duration of oral contraceptive use. Results for never-users of hormone therapy are additionally stratified by menopausal status/hysterectomy, and results for ever-users of hormone therapy are restricted to postmenopausal women. Relative risk estimates are plotted against the mean body mass index in each category (<25, 25–29, and 30+ kg/m²). Case–control studies with hospital controls are excluded.

Figure 5. Relative risk of ovarian cancer by tumour histology.

Relative risk¹ (RR¹) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy. Relative risk² (RR²) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, height, duration of oral contraceptive use, and ever use of hormone therapy. Case–control studies with hospital controls are excluded. The dotted line represents the overall result for all women with recorded histology. NOS, not otherwise specified; SE, standard error.