This manuscript is one of a series of papers by a group author, ‘The Collaborative Group on Epidemiological Studies of Ovarian Cancer’. Individual data from 47 separate studies have been submitted centrally by all collaborators listed in the Acknowledgments section. Each collaborator was responsible for the design of one or more of the 47 contributing epidemiological studies. All collaborators have seen this manuscript and a previous version, and their comments are incorporated here. Analyzed the data: VB CH RP GR. Wrote the first draft of the manuscript: VB CH RP GR. Contributed to the writing of the manuscript: Collaborators.
The authors have declared that no competing interests exist.
A reanalysis of published and unpublished data from epidemiological studies examines the association between height, body mass index, and the risk of developing ovarian cancer.
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 Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships.
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;
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.
Cancer of the ovaries, usually referred to as ovarian cancer, is the fifth leading cause of cancer death in women, and, unfortunately, symptoms (such as abdominal pain and swelling) usually occur late in the disease process; fewer than one-third of ovarian cancers are detected before they have spread outside of the ovaries. There is no definitive evidence that screening reduces mortality from ovarian cancer, and given the poor prognosis of advanced ovarian cancer, there has been much research over recent years to increase understanding of this serious condition. There are recognized risk factors that increase the chance of developing ovarian cancer, such as increasing age, having fewer children, not having used oral contraceptives, and use of menopausal hormone therapy. Age and oral contraceptive use have by far the biggest impact on ovarian cancer risk.
To date, there is no definitive information about the relevance of women's height, weight, and body mass index to their subsequent risk of developing ovarian cancer. There have been roughly 50 epidemiological studies of ovarian cancer, but only about half of these studies have published results on the association between body size and ovarian cancer risk, and so far, these findings have been inconsistent. Therefore, the researchers—an international collaboration of researchers studying ovarian cancer—re-analyzed the available epidemiological evidence to investigate the relationship between ovarian cancer risk and adult height, weight, and body mass index, and to examine the consistency of the findings across study designs.
After an extensive literature search, the researchers identified 47 eligible studies that collected individual data on women's reproductive history, use of hormonal therapies, height, weight, and/or body mass index, and in which the principal investigators of each study accepted the invitation from the researchers to be involved in the re-analysis. The researchers combined data from the different studies. To ensure that women in one study were only directly compared with controls (similar women without ovarian cancer) in the same study, all analyses were routinely stratified by study, center within study, age, parity, use of oral contraceptives, use of hormonal therapy for menopause, and menopausal status or hysterectomy.
The 47 studies were conducted in 14 countries and comprised a total of 25,157 women with ovarian cancer (mostly from Europe and North America) and 81,311 women without ovarian cancer. The researchers found a significant increase in relative risk (1.07) of ovarian cancer per 5 cm increase in height. Furthermore, this risk did not vary depending on other studied factors—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. However, the researchers found that for body mass index, the risks depended on whether women had ever taken menopausal hormone therapy: the relative risk for ovarian cancer per 5 kg/m2 increase in body mass index was 1.10 in women who had never taken menopausal hormone therapy but was only 0.95 in women who had previously taken menopausal hormone therapy.
These findings suggest that increasing height can be considered as a risk factor for ovarian cancer and that in women who have never taken menopausal hormone therapy, increased body mass index can be considered an additional risk factor. These findings have public health implications, especially in high-income countries, because the average height of women has increased by about 1 cm per decade and average body mass index has increased by about 1 kg/m2 per decade. The findings suggest an associated increase in ovarian cancer incidence of 3% per decade if all other factors relevant for ovarian cancer remain constant.
Please access these web sites via the online version of this summary at
The following organizations give more information on ovarian cancer which may be of use to patients:
About 50 epidemiological studies of ovarian cancer have collected information on the relevance of women's adult height and weight to their subsequent risk of ovarian cancer
Our collaboration began in 1998, and since then potentially eligible epidemiological studies have been sought regularly, by searches of review articles and through computer-aided literature searches in MEDLINE, EMBASE, and PubMed using combinations of the search terms “ovarian cancer”, “ovary cancer”, “height”, “body mass index”, “body size”, “anthropometr*”. To be eligible for these analyses, studies needed to have collected individual data on women's reproductive history, use of hormonal therapies, height, weight, and/or body mass index, studied at least 200 women with ovarian cancer, and published their findings before 1 January 2009. (Before 2006, studies with fewer than 200 cases of ovarian cancer had been eligible, and so there are fewer cases in some studies.) Studies that had collected relevant data but had not published on ovarian cancer and body size were sought by correspondence with colleagues, by discussions at collaborators meetings (in 2000, 2005, and 2011), and by electronic searches using the additional terms “cohort”, “prospective”, “women”, and “cancer risk”.
We identified 51 eligible studies and invited principal investigators from each study to participate in the collaboration. Investigators from just one eligible study
“Cases” are women with malignant epithelial or non-epithelial ovarian cancer and “controls” are women without ovarian cancer who had not undergone bilateral oophorectomy. Information sought from principal investigators about every control and about every case included their age, ethnic group, education, height, weight and/or body mass index, age at menarche, reproductive history, use of hormonal contraceptives, use of menopausal hormonal therapy, hysterectomy, family history of ovarian or breast cancer, and consumption of alcohol and tobacco. The information sought on these factors was for the time preceding the onset of disease for cases and for an equivalent time for controls. So that similar analytical methods could be used across studies, cohort studies were incorporated using a nested case–control design, in which up to four controls were selected at random and matched at follow-up by age of the case at entry into the cohort, age at cancer diagnosis, and, where appropriate, broad geographical region. In one cohort study “cases” were women with fatal ovarian cancer
Principal investigators of 47 epidemiological studies included in the analyses
Study (Country) [Reference] | Number of Cases/Controls | Median Year of Diagnosis (Cases) | Median Year of Birth (Cases) | Mean Age (Cases) | Mean Height (cm)/Mean Body Mass Index (kg/m2) (Controls) |
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Oxford/FPA (UK) |
49/196 | 1988 | 1937 | 48.1 | 161.5/22.9 |
BCDDP (US) |
353/1,381 | 1989 | 1923 | 65.3 | 162.0/25.3 |
Nurses' Health Study (US) |
677/2,710 | 1991 | 1930 | 58.7 | 163.7/25.3 |
Iowa Women's Health |
179/716 | 1991 | 1924 | 68.0 | 162.4/23.8 |
Radiation technologists (US) |
44/176 | 1992 | 1945 | 47.5 | 164.5/23.6 |
Netherlands Cohort (Netherlands) |
248/1,739 | 1992 | 1923 | 67.8 | 165.2/25.1 |
CNBSS (Canada) |
481/1,922 | 1993 | 1932 | 59.1 | 161.7/25.1 |
Norwegian Counties |
130/520 | 1993 | 1937 | 55.1 | 162.8/25.8 |
CPS-II Mortality (US) |
2,697/1,1367 | 1994 | 1923 | 70.3 | 162.9/24.8 |
Swedish mammography |
289/1,143 | 1996 | 1931 | 64.1 | 163.9/25.2 |
CPS-II Nutrition (US) |
355/1,419 | 1997 | 1929 | 67.8 | 163.8/25.6 |
WLH (Norway/Sweden) |
105/417 | 1998 | 1947 | 48.7 | 165.9/23.0 |
NIH-AARP (US) |
751/3,009 | 1999 | 1932 | 65.9 | 163.1/26.7 |
EPIC (eight European countries) |
444/1,788 | 2000 | 1935 | 63.7 | 161.3/25.6 |
NOWAC (Norway) |
102/414 | 2000 | 1940 | 59.8 | 164.8/25.0 |
PLCO (US) |
201/805 | 2001 | 1933 | 68.1 | 163.1/26.9 |
Million Women Study (UK) |
3,753/15,009 | 2002 | 1941 | 61.0 | 162.0/25.7 |
All prospective studies | 10,858/44,731 | 1999 | 1934 | 64.1 | 162.7/25.3 |
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Casagrande/Pike (US) |
150/150 | 1974 | 1932 | 40.2 | NA/22.9 |
Weiss (US) |
298/1,135 | 1977 | 1921 | 55.1 | 162.2/23.3 |
CASH (US) |
575/4,238 | 1981 | 1937 | 41.9 | 164.123.0 |
Whittemore (US) |
232/679 | 1984 | 1933 | 50.5 | NA/24.0 |
Shu/Brinton (China) |
228/229 | 1985 | 1933 | 48.4 | 158.5/22.1 |
Western New York (US) |
122/692 | 1988 | 1930 | 58.4 | 162.9/25.6 |
Risch (Canada) |
450/564 | 1991 | 1934 | 56.7 | 162.9/24.5 |
Green/Purdie (Australia) |
784/853 | 1992 | 1935 | 55.1 | 162.0/24.2 |
Mosgaard (Denmark) |
905/1,093 | 1992 | 1943 | 45.9 | 166.5/23.7 |
Cramer (US) |
563/525 | 1993 | 1942 | 51.1 | 162.9/25.3 |
Riman (Sweden) |
807/3,875 | 1994 | 1932 | 61.5 | 163.8/25.3 |
German OCS |
281/531 | 1995 | 1937 | 55.2 | 163.9/22.1 |
Pike/Wu (US) |
477/660 | 1995 | 1939 | 55.5 | 163.6/23.4 |
Goodman/Wu (US) |
719/892 | 1996 | 1942 | 55.0 | 159.0/24.5 |
NISOC study (Israel) |
1,237/2,103 | 1996 | 1939 | 56.0 | 161.0/25.0 |
OVCARE (US) |
376/1,637 | 1996 | 1950 | 45.7 | 165.0/24.9 |
SHARE (US) |
767/1,364 | 1996 | 1943 | 51.6 | 162.5/25.9 |
All with population controls | 8,971/21,220 | 1994 | 1939 | 52.7 | 163.2/24.3 |
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Byers (US) |
163/753 | 1960 | 1908 | 52.3 | NA/26.4 |
Newhouse (UK) |
280/582 | 1973 | 1918 | 54.1 | 160.7/NA |
McGowan (US) |
182/192 | 1975 | 1923 | 50.4 | NA//23.3 |
Paffenbarger (US) |
110/480 | 1975 | 1917 | 55.6 | NA/24.1 |
Hildreth/Kelsey (US) |
62/1,047 | 1978 | 1918 | 60.1 | NA/24.9 |
Hartge (US) |
293/333 | 1979 | 1924 | 54.3 | NA/23.2 |
Booth (UK) |
286/489 | 1980 | 1927 | 50.9 | 162.8/24.1 |
Rosenberg (US) |
952/3,808 | 1983 | 1935 | 49.5 | 162.8/26.6 |
Negri/Franceschi(Italy) |
957/2,478 | 1986 | 1932 | 53.1 | 160.9/23.8 |
PEDS (US) |
411/1,752 | 1989 | 1933 | 54.5 | 162.5/25.5 |
Tzonou/Tricopoulos (Greece) |
319/396 | 1990 | 1929 | 56.0 | 160.9/24.7 |
Negri (Italy) |
1026/2,398 | 1995 | 1939 | 54.9 | 161.1/25.3 |
Zhejiang-Curtin (China) |
287/652 | 1999 | 1952 | 46.3 | 158.3/22.1 |
All with hospital controls | 5,328/15,360 | 1986 | 1932 | 52.7 | |
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NA, not available.
Information on the histological classification of the ovarian cancers was provided by principal investigators of all but seven
The analytical methods were similar to those used previously
To ensure that women in one study were compared directly only with similar women in the same study, all analyses were routinely stratified by study, by centre within study, by age (in 5-y age groups, with women aged over 90 y excluded), parity (0, 1+), use of oral contraceptives (no, for <5 y, 5+ y), ever use of hormonal therapy for the menopause (yes, no), and menopausal status or hysterectomy (pre/perimenopausal, natural menopause before age 50, natural menopause after age 50, previous hysterectomy, other). Unknowns for each stratification variable were assigned to separate strata. Analyses in relation to height were also adjusted by body mass index, and analyses in relation to body mass index and to weight were also adjusted by height; results of sensitivity analyses to assess the effect of these mutual adjustments are presented. The effect on the main findings of other potential confounding factors (year of birth, ethnic group, education, family history of ovarian or breast cancer, age at menarche, menopausal status, alcohol use, and smoking) was examined by comparing results before and after stratification for each variable, in turn, and all simultaneously.
The relative risk of ovarian cancer per 5 cm increase in height and per 5 kg/m2 increase in body mass index was estimated by fitting a log-linear trend across categories of height (<155, 155–, 160–, 165–, 170–, 175+ cm) and body mass index (<20, 20–, 22.5–, 25–, 27.5–, 30–, 32.5–, 35+ kg/m2) using the median value within each category.
Results in the figures are presented by squares and lines, respectively, representing the relative risks and their corresponding 95% or 99% CIs or g-s CIs. The position of the square indicates the value of the relative risk, and its area is inversely proportional to the variance of the logarithm of the relative risk, thereby providing an indication of the amount of statistical information available for that particular estimate. When results from many studies or many subgroups are presented in the figures, 99% CIs/g-s CIs are given, since because of the multiple testing,
In high-income countries the average height has increased by about 1 cm per decade
Details of the women in the 47 participating studies are shown in
Ovarian cancer risk increased significantly both with increasing height and with increasing body mass index (
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.
The taller women were, the greater was their risk of ovarian cancer (
Factor | Cases/Controls | Relative Risk |
Relative Risk |
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<160 (154.8) | 5,221/18,334 | 1.00 (0.95–1.05) | 1.00 (0.95–1.05) |
160– (161.7) | 5,678/19,231 | 1.09 (1.05–1.14) | 1.10 (1.05–1.16) |
165– (166.5) | 4,961/16,498 | 1.14 (1.09–1.20) | 1.15 (1.10–1.21) |
170+ (172.7) | 3,587/11,059 | 1.24 (1.17–1.32) | 1.27 (1.20–1.35) |
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<60 (54.1) | 5,870/19,904 | 1.00 (0.96–1.05) | 1.00 (0.95–1.05) |
60–69 (64.2) | 6,379/22,197 | 1.04 (1.00–1.08) | 1.02 (0.97–1.06) |
70–79 (73.7) | 3,939/13,183 | 1.11 (1.05–1.17) | 1.07 (1.02–1.14) |
80+ (90.3) | 3,114/9,128 | 1.24 (1.17–1.32) | 1.18 (1.10–1.26) |
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<22.5 (20.6) | 6,299/21,009 | 1.00 (0.96–1.05) | 1.00 (0.95–1.05) |
22.5– (23.5) | 4,024/13,554 | 1.04 (0.99–1.10) | 1.05 (1.00–1.11) |
25– (25.9) | 4,351/14,790 | 1.07 (1.02–1.12) | 1.08 (1.02–1.13) |
27.5– (28.4) | 1,771/5,892 | 1.07 (0.99–1.16) | 1.07 (0.99–1.17) |
30+ (33.6) | 3,043/9,435 | 1.12 (1.05–1.19) | 1.13 (1.06–1.20) |
Test for trend: height,
Relative risk stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, duration of oral contraceptive use, and ever use of menopausal hormone therapy.
Relative risk stratified as for the previous column, with additional stratification by body mass index (for height) and by height (for weight and body mass index).
The magnitude of the increase in the relative risk of ovarian cancer with increasing height did not vary substantially by age, year of birth, education, age at menarche, parity, use of oral contraceptives, menopausal status, use of menopausal hormone therapy, hysterectomy, smoking, alcohol consumption, or having first degree relatives with breast or ovarian cancer (
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.
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.
The heavier and the more obese women were, the greater was their risk of ovarian cancer (
The magnitude of the increase in the relative risk of ovarian cancer with increasing body mass index did not vary significantly by women's age, year of birth, ethnic group, education, age at menarche, parity, use of oral contraceptives, menopausal status, hysterectomy, alcohol and tobacco use, or family history of breast or ovarian cancer (
Results in prospective studies were not significantly different when the first 4 y of follow-up were excluded. The risk estimates associated with body mass index in ever-users and never-users of hormone therapy changed by less than 2% after further adjustment for seven other potential confounding factors: ethnic group, education, age at first birth, family history of ovarian or breast cancer, age at menarche, and alcohol and tobacco consumption, and simultaneous adjustment for all these factors also affected the relative risk estimate by less than 2%. Since factors other than hormone use did not have a major effect on the relationship between ovarian cancer and body mass index, the main results are summarized in
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.
Data on tumour histology was available for 17,039 (68%) women with ovarian cancer included in the main analyses. The effects of increasing height and increasing body mass index did not differ significantly between epithelial and non-epithelial tumours or between clear cell, endometrioid, mucinous, or serous 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.
Based on the findings here, a 1 cm increase in height is associated with a relative risk of ovarian cancer of 1.014, and a 1 kg/m2 increase in body mass index with a relative risk of 1.019, in never-users of hormone therapy. In high-income countries, where average height has increased by about 1 cm per decade
Our collaboration has brought together and re-analysed individual data from 47 studies on ovarian cancer risk associated with adult height, weight, and body mass index, that is, most of the available epidemiological information worldwide. Collectively, the findings show a highly significant increase in the risk of ovarian cancer with increasing values for each of the anthropometric variables examined. The increase in ovarian cancer risk with increasing height and with increasing body mass index did not vary materially by women's age, year of birth, ethnicity, education, age at menarche, parity, family history of ovarian or breast cancer, use of oral contraceptives, menopausal status, hysterectomy, or consumption of alcohol and tobacco. However use of hormone therapy for the menopause attenuated the relationship with body mass index, since an increase in ovarian cancer risk with increasing adiposity was found only in never-users of such therapy. The trends with increasing height and body mass index were broadly similar across the common histological subtypes of ovarian cancer, except for serous tumours of borderline malignancy, which comprise 5% of the total, where the increase in risk with increasing body mass index was considerably greater than for the other tumour subtypes.
An advantage of seeking to review all epidemiological studies of ovarian cancer with relevant information on body size, published and unpublished, is that this helps avoid unduly selective emphasis on published results or just on some studies. Three eligible studies that did not contribute data to these analyses but that had published on ovarian cancer risk associated with height and/or body mass index,
Results from case–control studies that used hospital controls differ qualitatively and significantly from those with other study designs. It seems unlikely that these differences are due to the retrospective reporting of height and/or weight, since the results differ substantially between the retrospective studies that used hospital controls and the retrospective studies that used population controls. While other factors might also be relevant, many of the retrospective studies with hospital controls were designed to examine the effects of hormonal factors on ovarian cancer risk, and controls were often recruited from orthopaedic wards, where the most common reason for admission among middle-aged women is for hip and knee replacement surgery, and the risk of these conditions increases markedly with increasing height and increasing body mass index
In prospective studies, height and weight were generally recorded at the time that women were recruited into the cohort, and in case–control studies, women were generally asked about their height and weight some 1–5 y before the diagnosis of ovarian cancer (for cases) and at an equivalent time for controls. In the case–control studies with population controls, the retrospective reporting of height and weight may have been influenced by the cases' knowledge that they had ovarian cancer, but the similarity of the findings in such studies and in those with prospective recording of anthropometric factors suggests that this is probably not a serious problem here. Nonetheless, there is still likely to be some measurement error, not only in retrospective self-reported data but also with measurements made at entry into a prospective study, because women's weight (and, to a lesser extent, their height) may change over time. Non-differential misclassification of these variables would dilute estimates of relative risk, although the effects are likely to be comparatively small
The observed association between ovarian cancer and height did not differ significantly between prospective studies and retrospective studies with population controls, nor did it vary by the 12 personal characteristics of the women that were examined (
The association between ovarian cancer and body mass index is seen across all subgroups of women studied, except ever-users of menopausal hormone therapy. The relevance of the finding in users of menopausal hormones will be examined in a future report from this collaboration, where the direct relationship between ovarian cancer risk and use of menopausal hormone therapy will be examined, and the potential modification of any effect of hormone therapy by women's adiposity and other factors will be explored. Body mass index is in general a good measure of adiposity, although women with the same value for the index may vary in the relative contribution from fat and from muscle. The finding that use of hormone therapy largely eliminates the relationship between body mass index and ovarian cancer risk suggests that endogenous oestrogens may be relevant, at least among postmenopausal women: the well-characterized association between circulating oestrogen levels and increasing adiposity in postmenopausal women who do not use hormonal therapies is likely to be altered among users of these therapies
Among women in high-income countries, average height has increased by about 1 cm per decade and average body mass index has increased by about 1 kg/m2 per decade in the generations of women now developing ovarian cancer
(DOC)
The following are the members of the Collaborative Group on Epidemiological Studies of Ovarian Cancer.
confidence interval
group-specific confidence interval