BRIEF COMMUNICATION

Height, Body Mass Index, and Ovarian Cancer: A Follow-Up of 1.1 Million Norwegian Women

Anders Engeland, Steinar Tretli, Tone Bjørge

Affiliations of authors: A. Engeland, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; S. Tretli, The Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo; T. Bjørge, Department of Pathology, The Norwegian Radium Hospital, Oslo.

Correspondence to: Anders Engeland, MSc, PhD, Division of Epidemiology, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway (e-mail: anders.engeland{at}fhi.no).

ABSTRACT

Body mass index (BMI) has shown both positive and negative associations with ovarian cancer. Whether a possible association between height and ovarian cancer exists is unknown. We explored whether BMI and height were associated with ovarian cancer risk in a Norwegian cohort of approximately 1.1 million women, aged 14–74 years who were measured between 1963 and 1999. The cohort was followed for an average of 25 years through linkage to population-based cancer and death registries. Among the cohort, 7882 histologically verified cases of ovarian cancer were registered. Relative to women with a medium BMI (18.5–24.9 kg/m2), women who were overweight or obese in adolescence or young adulthood had an increased risk of ovarian cancer; women with a very high BMI in adolescence had a relative risk of 1.56 (95% confidence interval = 1.04 to 2.32) compared with women with medium BMI. No such association was seen in older women. A positive association between height and risk of ovarian cancer, particularly endometrioid ovarian cancer, was observed in women younger than 60 years of age.


In 1990, ovarian cancer was the sixth most common cancer among women worldwide (1). In Norway, the incidence of ovarian cancer has increased moderately since 1970 (2). Body mass index (BMI) has been shown to have both positive and negative associations with ovarian cancer (36). From a recent systematic review of the literature, it was concluded that the evidence is in favor of a small-to-moderate positive relation between high BMI and ovarian cancer risk (5).

Prospective studies have found a positive association between height and cancer risk, most consistently in relation to breast cancer (7). Associations between body height and ovarian cancer risk have received less attention (7,8). Here, we explored the relationship between both height and BMI and the risk of ovarian cancer in a cohort of approximately 1.1 million women aged 14–74 years.

From 1963 through 1975, height and weight were measured as part of a tuberculosis screening program among the general Norwegian population (9). From 1963 through 1964 and from 1974 through 1999, height and weight were also measured in other health surveys (mainly to screen for cardiovascular disease risk) in different parts of Norway (1012). Height and weight were measured in a standardized way by trained staff. A total of 1 415 965 measurements from 1 068 128 women (111 886 measurements from women aged 14–19 years; 1 025 283 measurements from women aged 20–74 years) were available. When more than one measurement was available, the earliest measurement taken within each age group (14–19 years and 20–74 years, respectively) was used. Some women (n = 69 041) were measured both in adolescence and in adulthood and are included in both cohorts. Details regarding the cohorts, including the relation between BMI and mortality, are described elsewhere (13,14).

Since 1960, all individuals who reside in Norway have been assigned a unique 11-digit identification number. Deaths and emigrations among members of the cohorts were identified by linkage of the identification number to the Death Registry at Statistics Norway. All women diagnosed with ovarian cancer (International Classification of Diseases, seventh revision [ICD-7], code 175) in the cohorts were identified by linkage to the Cancer Registry of Norway (1517).

Of the ovarian tumors diagnosed among members of the cohorts, 98% were verified histologically. For our analysis, the first histologically verified invasive ovarian cancer was included for each woman. Women with a diagnosis of ovarian cancer before the measurements were excluded from analysis (n = 758). The cohort members were followed until the date of a first ovarian cancer diagnosis, emigration, age 100, death, or June 30, 2001, whichever came first. Only 13 women in the study population (1 067 370 women) were lost to follow-up. By the end of follow-up, 68.3% were alive without a diagnosis of ovarian cancer, 31.0% were dead (all causes), and 0.7% had been diagnosed with ovarian cancer. Of those alive, 1.1% had emigrated from Norway.

To assess the risk of ovarian cancer, Cox proportional hazards regression models were fitted with time since measurement as the time variable (18). In the analyses, BMI, defined as weight in kilograms divided by height in meters squared, was categorized for those aged 14–19 years, following the guidelines from Centers for Disease Control and Prevention/National Center for Health Statistics (19,20) by using growth percentiles (low, <25th; medium, 25th–74th; high, 75th–84th; and very high, >=85th percentile) from a U.S. reference population. For those aged 20 years or older, BMI was categorized following the recommendation of the World Health Organization (21) (BMI<18.5, underweight; 18.5–24.9, normal; 25.0–29.9, pre-obese/ overweight; and >=30.0, obese). Height in centimeters was categorized into 5-cm groupings (<150, 150–154, . . ., 170–174, and >=175). Separate analyses were performed for serous, mucinous, and endometrioid ovarian cancers. SPSS (22) was used to derive relative risks (RRs) of ovarian cancer with 95% confidence intervals (CIs).

A total of 1 067 357 women (mean age = 42 years) were followed for an average of 24.7 years (range = 0–38). A total of 7882 women were diagnosed with ovarian cancer (98 women diagnosed with ovarian cancer were included in both cohorts), of which 94.4% were of epithelial origin. Mean age at diagnosis was 62 years. For the cancer patients, the BMI measurements were made on average 16.7 years before diagnosis.

Among 111 883 women measured in adolescence and followed for an average of 31.6 years, 260 were diagnosed with ovarian cancer, of which 88% were of epithelial origin (Table 1Go). The mean age at measurement was 17 years; 81% of the girls had a low or medium BMI, 11% had a high BMI, and 8% had very high BMI. The mean age at diagnosis was 41 years. Compared with girls with a medium BMI, girls with a high or very high BMI had an RR of ovarian cancer of 1.43 (95% CI = 1.00 to 2.04) and 1.56 (95% CI = 1.04 to 2.32), respectively (Table 2Go). Ending the follow-up at age 50 years, the RRs of ovarian cancer for girls with a high or very high BMI were 1.39 (95% CI = 0.95 to 2.04) and 1.74 (95% CI = 1.16 to 2.60), respectively.


View this table:
[in this window]
[in a new window]
 
Table 1. Number of women (N), number of ovarian cancer cases, observed person-years, and overall ovarian cancer rates in women measured in adolescence and adulthood
 

View this table:
[in this window]
[in a new window]
 
Table 2. Relative risk (RR) of ovarian cancer with 95% confidence intervals (CIs) from Cox regression analysis, adjusted for age at measurement and birth cohort, according to body mass index (BMI) and height
 
Among the 1 024 468 women measured in adulthood (ages 20–74 years) and followed for an average of 23.0 years, 7720 were diagnosed with ovarian cancer, of which 95% were of epithelial origin (Table 1Go). The mean age at diagnosis was 63 years. Of all the women, 2% were underweight, 55% had a BMI within the normal range, 30% were overweight, and 13% were obese.

The risk of ovarian cancer was not associated with adult BMI (Table 2Go). If follow-up was ended at age 50 years, there was a tendency toward an increased risk of ovarian cancer in obese women (RR = 1.21, 95% CI = 0.97 to 1.50) relative to women who had a BMI within the normal range. To exclude the possibility that, at the time of the BMI measurement, weight was influenced by the presence of an undiagnosed ovarian cancer, we analyzed the data after omitting the first 5 years of follow-up and found similar results. Increasing height was associated with an increasing risk of ovarian cancer (Table 2Go), most pronounced in women younger than 60 years (data not shown).

Results from age-stratified analyses suggested that women who were obese in their twenties had an increased risk of ovarian cancer (RR = 1.45, 95% CI = 1.02 to 2.04) compared with women whose BMI was between 18.5 and 25 kg/m2 (Table 3Go).


View this table:
[in this window]
[in a new window]
 
Table 3. Relative risk (RR) of ovarian cancer with 95% confidence intervals (CIs) by age at measurement from Cox regression analysis by body mass index (BMI), adjusted for birth cohort (seven categories)
 
We next assessed whether there was an association between histologic subtype and adult BMI. Of all ovarian cancer cases, 44% were serous, 9% were mucinous, and 11% were endometrioid. BMI was not associated with any histologic subtype. However, the risk of endometrioid cancer increased with increasing height (Ptrend = .001).

We explored the relationship between BMI and ovarian cancer risk in a large cohort of Norwegian women. The variables available in the present study were measured height and weight, date of measurement, and age. By contrast with the American Cancer Prevention Study II (CPS-II) and the Nurses’ Health Study (NHS), we used measured height and weight. Self-reported height and weight have been shown to vary systematically with BMI (2325). In two large American studies of BMI and ovarian cancer risk, adjustments were made for several possible confounders such as oral contraceptive use, parity, age at menarche, smoking, and tubal ligation history (26,27). This adjustment led to only minor changes in the associations, with the exception of an increased risk of ovarian cancer in women who never used postmenopausal estrogens (26). Because we had no information on estrogen use, we performed separate analyses for women born before 1940. The risk of ovarian cancer did not increase with increasing BMI in women born before 1940 (data not shown). The use of exogenous estrogens was probably low in these women; during 1985–1988, less than 6% of postmenopausal women aged 40–54 years in some Norwegian counties were current users of hormone replacement therapy (28).

Using data from CPS-II, Rodriguez et al. (26) studied the impact of BMI and height on cancer mortality in 300 000 women. They found an increased risk of ovarian cancer mortality in overweight (BMI>=25 kg/m2) and obese (BMI>=30 kg/m2) women relative to women whose BMI was below 25 kg/m2. Rodriguez et al. (26) speculated that ovarian cancer, similar to breast cancer, is associated with obesity only among postmenopausal women. No association between adult BMI and the risk of ovarian cancer was found in the NHS (27). Another study using data from the NHS found no association between intake of fat and ovarian cancer risk (29). However, a positive association between BMI at age 18 years (self-reported at age 30–55 years) and premenopausal ovarian cancer was found in the NHS (27). Another study (30) also found an association between increased BMI at age 18 years and ovarian cancer risk. In age-stratified analyses, we found no excess risk in overweight or obese women aged 50 years or older but, in concordance with Fairfield et al. (27), our analyses indicated that obesity in adolescence/young adulthood increased the risk of ovarian cancer. Higher endogenous androgen levels and lower circulating progesterone levels are possible explanations for the increased ovarian cancer risk in women who are obese during adolescence (27,31).

Several case–control studies have explored the relation between BMI and ovarian cancer risk (5,32) and between height and ovarian cancer risk (7). A recent review concluded that there was a small-to-moderate positive relation between high BMI and ovarian cancer risk (5), but no consistent picture was seen in five case–control studies (7) examining the relation between height and ovarian cancer risk. However, the positive association between height and ovarian cancer risk found in our study, although confined to women younger than 60 years, is consistent with the findings of Rodriguez et al. (26). In addition, we found a particularly strong positive association between height and endometrioid ovarian cancer risk. In a recent Dutch study, a positive relation was observed in postmenopausal women (33). Insulin-like growth factors may play a role in the development of cancer, and height may act as a marker for the levels of these growth factors (7). Furthermore, height may be an indicator that early-life conditions are connected to cancer risk.

In summary, we observed a positive association between BMI and risk of ovarian cancer in young women. A positive association between height and the risk of ovarian cancer, particularly endometrioid ovarian cancer, was observed in women younger than 60 years.

We are grateful to those who during almost 40 years have collected the data used in the present study. These are persons connected to the former National Health Screening Service, the Nord-Trøndelag Health Survey (HUNT), the Hordaland Health Survey (HUSK), and the Tromsø Study.

REFERENCES

1 Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–41.[CrossRef][ISI][Medline]

2 Bjørge T, Engeland A, Hansen S, Trope CG. Trends in the incidence of ovarian cancer and borderline tumours in Norway, 1954–1993. Int J Cancer 1997;71:780–6.[CrossRef][ISI][Medline]

3 Farrow DC, Weiss NS, Lyon JL, Daling JR. Association of obesity and ovarian cancer in a case-control study. Am J Epidemiol 1989;129:1300–4.[Abstract]

4 Purdie D, Green A, Bain C, Siskind V, Ward B, Hacker N, et al. Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Survey of Women’s Health Study Group. Int J Cancer 1995;62:678–84.[ISI][Medline]

5 Purdie DM, Bain CJ, Webb PM, Whiteman DC, Pirozzo S, Green AC. Body size and ovarian cancer: case-control study and systematic review (Australia). Cancer Causes Control 2001;12:855–63.[CrossRef][ISI][Medline]

6 Lukanova A, Toniolo P, Lundin E, Micheli A, Akhmedkhanov A, Muti P, et al. Body mass index in relation to ovarian cancer: a multi-centre nested case-control study. Int J Cancer 2002;99:603–8.[CrossRef][ISI][Medline]

7 Gunnell D, Okasha M, Smith GD, Oliver SE, Sandhu J, Holly JM. Height, leg length, and cancer risk: a systematic review. Epidemiol Rev 2001;23:313–42.[ISI][Medline]

8 Polychronopoulou A, Tzonou A, Hsieh CC, Kaprinis G, Rebelakos A, Toupadaki N, et al. Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. Int J Cancer 1993;55:402–7.[ISI][Medline]

9 Waaler HT. Height, weight and mortality. The Norwegian experience. Acta Med Scand Suppl 1984;679:1–56.[Medline]

10 Bjartveit K, Foss OP, Gjervig T, Lund-Larsen PG. The cardiovascular disease study in Norwegian counties. Background and organization. Acta Med Scand Suppl 1979;634:1–70.[Medline]

11 Bjartveit K. The National Health Screening Service: From fight against tuberculosis to many-sided epidemiological activities. Nor Epidemiol 1997;7:157–74.

12 Tverdal A. Prevalence of obesity among persons aged 40–42 years in two periods. Tidsskr Nor Laegeforen 2001;121:667–72.[Medline]

13 Engeland A, Bjørge T, Selmer RM, Tverdal A. Height and body mass index in relation to total mortality. Epidemiology 2003;14:293–9.[CrossRef][ISI][Medline]

14 Engeland A, Bjørge T, Søgaard AJ, Tverdal A. Body mass index in adolescence in relation to total mortality: 32-year follow-up of 227,000 Norwegian boys and girls. Am J Epidemiol 2003;157:517–23.[Abstract/Free Full Text]

15 Tingulstad S, Halvorsen T, Norstein J, Hagen B, Skjeldestad FE. Completeness and accuracy of registration of ovarian cancer in the cancer registry of Norway. Int J Cancer 2002;98:907–11.[CrossRef][ISI][Medline]

16 The Cancer Registry of Norway. Cancer in Norway 2000. Oslo (Norway): The Cancer Registry of Norway; 2002. p. 1–91.

17 The Cancer Registry of Norway. April 2003. Available at: http://www.kreftregisteret.no/. [Last accessed: June 20, 2003.]

18 Cox DR, Oakes D. Analysis of survival data. London (U.K.): Chapman and Hall Ltd.; 1984. p. 1–201.

19 National Center for Health Statistics. CDC Growth Charts: August 2002. United States. Available at: http://www.cdc.gov/growthcharts/. [Last accessed: June 20, 2003.]

20 Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data 2000;314:1–27.[Medline]

21 World Health Organization (WHO) Consultation on Obesity. Preventing and managing the global epidemic: Report of a WHO Consultation on Obesity, Geneva, 3–5 June 1997. Geneva (Switzerland): WHO; 1998. p. 1–276.

22 SPSS for Windows. Release 11.0.1. 2001.

23 Plankey MW, Stevens J, Flegal KM, Rust PF. Prediction equations do not eliminate systematic error in self-reported body mass index. Obes Res 1997;5:308–14.[Abstract]

24 Nawaz H, Chan W, Abdulrahman M, Larson D, Katz DL. Self-reported weight and height: implications for obesity research. Am J Prev Med 2001;20:294–8.[CrossRef][ISI][Medline]

25 Kuczmarski MF, Kuczmarski RJ, Najjar M. Effects of age on validity of self-reported height, weight, and body mass index: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Am Diet Assoc 2001;101:28–34.[CrossRef][ISI][Medline]

26 Rodriguez C, Calle EE, Fakhrabadi-Shokoohi D, Jacobs EJ, Thun MJ. Body mass index, height, and the risk of ovarian cancer mortality in a prospective cohort of postmenopausal women. Cancer Epidemiol Biomarkers Prev 2002;11:822–8.[Abstract/Free Full Text]

27 Fairfield KM, Willett WC, Rosner BA, Manson JE, Speizer FE, Hankinson SE. Obesity, weight gain, and ovarian cancer. Obstet Gynecol 2002;100:288–96.[Abstract/Free Full Text]

28 Graff-Iversen S, Stensvold I, Lund-Larsen PG, Nodarse LO, Tverdal A, Urdal P. Serum lipids in postmenopausal or perimenopausal women using estrogen alone, estrogen with levonorgestrel, or estrogen with norethisterone, compared with nonusers: results from a cross-sectional study in two Norwegian counties 1985–1988. J Clin Epidemiol 1998;51:1311–6.[CrossRef][ISI][Medline]

29 Bertone ER, Rosner BA, Hunter DJ, Stampfer MJ, Speizer FE, Colditz GA, et al. Dietary fat intake and ovarian cancer in a cohort of US women. Am J Epidemiol 2002;156:22–31.[Abstract/Free Full Text]

30 Lubin F, Chetrit A, Freedman LS, Alfandary E, Fishler Y, Nitzan H, et al. Body mass index at age 18 years and during adult life and ovarian cancer risk. Am J Epidemiol 2003;157:113–20.[Abstract/Free Full Text]

31 Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 1998;90:1774–86.[Abstract/Free Full Text]

32 Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992;136:1212–20.[Abstract]

33 Schouten LJ, Goldbohm RA, van den Brandt PA. Height, weight, weight change, and ovarian cancer risk in the Netherlands cohort study on diet and cancer. Am J Epidemiol 2003;157:424–33.[Abstract/Free Full Text]

Manuscript received February 11, 2003; revised June 3, 2003; accepted June 6, 2003.


This article has been cited by other articles in HighWire Press-hosted journals:


             
Copyright © 2003 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement