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Is childhood body fatness an early marker of ovarian cancer risk?

Authors:
Kevin L'Espérance at Stanford University
Kevin L'Espérance
Jennifer Lee O'Loughlin at Université de Montréal
Jennifer Lee O'Loughlin
Anita Koushik at Université de Montréal
Anita Koushik
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Abstract

Introduction: Based on evidence indicating weak positive associations, expert panels have concluded that excess body fat is probably a cause of ovarian cancer. Most studies have used measures of adult body fatness, but hormonal disturbances by excess body fat in childhood may contribute to risk, which has been examined in only a few previous studies. Also, ovarian cancers are heterogenous and the risk may vary by tumour behaviour and histology. We investigated the relationship between childhood body fatness and ovarian cancer risk in a population-based case-control study conducted in Montreal, Canada (2011-2016). Methods: In total, 497 cases and 902 controls reported their body fatness at ages 5 and 10 years using pictograms of body silhouettes. Excess body fat was defined as being above the 85th percentile, based on the distribution of fatness among controls. Multivariate polytomous logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (95%CI) for the association according to tumour behaviour and histology. Results: Excess body fat in childhood was not associated with borderline serous or mucinous cancers, nor with invasive mucinous cancers. For invasive serous and endometrioid cancers, the ORs (95%CI) for excess body fat at age 10 were 1.40 (1.01-1.96) and 2.23 (1.20-4.12), respectively. These ORs were slightly weaker for body fatness at age 5. Conclusions: This study suggests that childhood may be a crucial period in the pathogenesis of ovarian cancer. Excess body fat in children represents a plausible early target for ovarian cancer prevention.
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Is childhood body fatness an early marker of ovarian cancer risk?
L’Espérance, K.1,2 O’Loughlin, J.1,2 Koushik, A.1,2
1 Carrefour de l’innovation, Université de Montréal Hospital Research Centre, Montréal, Québec
2Department of Social and Preventive Medicine, Université de Montréal School of Public Health, Montréal, Québec
At 5 years old
At 10 years old
ORs (95% CI)1
ORs (95% CI)1
All EOC
1.08 (0.98-1.19)
1.07 (0.97-1.18)
Borderline cancers (n=134)
0.96 (0.82-1.13)
0.97 (0.83-1.13)
Invasive cancers (n=363)
1.13 (1.02-1.26)
1.11 (1.00-1.23)
Type I (n=102)
1.16 (0.96-1.39)
1.17 (0.98-1.39)
Type II (n=261)
1.12 (1.00-1.26)
1.09 (0.97-1.22)
2. Objective
1. Background
To determine the association between childhood body fatness and
the risk of epithelial ovarian cancer (EOC), overall and according
to subtypes (i.e. tumour behaviour and histology).
3. Study design
vRecalled body shape at ages 5 and 10 years, based on the
Collins scale (Figure 1), represented childhood body fatness.
vChildhood body fatness was analyzed as a continuous variable
(per increment of one unit).
Figure 1. Measurement of childhood body shape (adapted from Collins, 1991)
Table 1. Adjusted ORs and 95%CI for childhood body fatness in relation to
overall, borderline, and invasive EOC
All models included 902 controls. 1Adjusted for age, number of full-term pregnancies, duration of oral
contraceptive use, and highest level of education.
6. Results
vIncreasing childhood body fat did not increase the risk of
EOC overall (Table 1).
vFor invasive EOC, positive associations were suggested,
but not for borderline EOC where null associations were
observed (Table 1).
Figure 2. Multivariate odds ratio (95% confidence intervals) for the
relation between childhood body fatness and EOC risk, by tumour
behaviour and histologic subtypes.
vBody fatness in childhood was not associated with borderline
serous or mucinous cancers, nor with invasive mucinous
cancers (Figure 2).
vFor serous and endometrioid invasive cancers, increasing
body fatness in childhood was associated with an increasing
risk. (Figure 2).
7. Discussion
vThis research suggests that childhood may be an important
period in ovarian cancer carcinogenesis.
vExcess body fat in children represents a plausible early
target for ovarian cancer prevention.
11. References
[1] Brenner, D. R., Weir, H. K., Demers, A. A., Ellison, L. F., Louzado, C., Shaw, A., . . . Canadian Cancer Statistics
Advisory, C. (2020). Projected estimates of cancer in Canada in 2020. CMAJ, 192(9), E199-E205.
doi:10.1503/cmaj.191292
[2] Henderson, J. T., Webber, E. M., & Sawaya, G. F. (2018). Screening for Ovarian Cancer: Updated Evidence
Report and Systematic Review for the US Preventive Services Task Force. JAMA, 319(6), 595-606.
doi:10.1001/jama.2017.21421
[3] World Cancer Research Fund/American Institute for Cancer Research. (2018). Diet, nutrition, physical activity
and ovarian cancer. Retrieved from https://www.wcrf.org/sites/default/files/Ovarian-cancer-report.pdf
[4] Collins, M. E. (1991). Body figure perceptions and preferences among preadolescent children. International
Journal of Eating Disorders, 10(2), 199-208.
[5] Koushik, A., Grundy, A., Abrahamowicz, M., Arseneau, J., Gilbert, L., Gotlieb, W. H., . . . Siemiatycki, J. (2017).
Hormonal and reproductive factors and the risk of ovarian cancer. Cancer Causes Control, 28(5), 393-403.
[6] Must, A., Willett, W. C., & Dietz, W. H. (1993). Remote recall of childhood height, weight, and body build by
elderly subjects. Am J Epidemiol, 138(1), 56-64.
10. Funding
vExpert panels have stated that body fatness is probably a cause
of ovarian cancer. This conclusion is based on the
epidemiological evidence suggesting a weak positive association.
vHowever, past studies may have been limited in observing a
stronger association because:
1Most studies measured body fatness in late adulthood,
possibly having excluded the etiologically relevant period for
ovarian cancer.
2Few studies have examined associations by tumour behaviour
and/or histology, which would not take into account the
heterogeneity of ovarian cancers, and possible differences in
association with body fatness
vBody fatness influences hormone levels during all stages of the
life course in women; we hypothesize that excess body fatness in
childhood may be pertinent as a risk factor for ovarian cancer. 9. Directed acyclic graph
4. Assessment and definition of childhood
body fatness
5. Analysis
vUnconditional logistic regression was used to estimate the
adjusted odds ratio (OR) and the 95% confidence interval
(95%CI) for EOC overall.
vMultivariate polytomous logistic regression was used to
estimate the adjusted ORs and the 95%CI by EOC subtypes.
vCovariates were selected using an evidence-based directed
acyclic graph (Figure 3). All models were adjusted for age,
number of full-term pregnancies, duration of oral contraceptive
use and highest level of education.
8. Conclusion
vIn this population-based study, factors affecting participation
(i.e. age and education) were accounted for (Figure 3).
vRecall of childhood factors may be difficult, but recall of body
shapes could be easier to recall than body weight.
vOther potential confounders were identified in the DAG (Figure
3), but uncontrolled confounding is possible.
Figure 3. DAG for the direct association between childhood body fatness
and ovarian cancer risk. The minimal sufficient adjustment set included
age, number of full-term pregnancies, duration of oral contraceptive use
and highest level of education.
8
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Hormonal and reproductive factors and the risk of ovarian cancer
Article
Full-text available
  • May 2017
  • CANCER CAUSE CONTROL
Purpose: Hormone-related factors have been associated with ovarian cancer, the strongest being parity and oral contraceptive use. Given reductions in birth rates and increases in oral contraceptive use over time, associations in more recent birth cohorts may differ. Furthermore, consideration of ovarian cancer heterogeneity (i.e., Type I/II invasive cancers) may contribute to a better understanding of etiology. We examined hormone-related factors in relation to ovarian cancer risk overall, for Type I and Type II cancers, as well as borderline tumors. Methods: A population-based case-control study was carried out in Montreal, Canada from 2011 to 2016, including 496 cases and 908 controls. For each hormone-related variable, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for ovarian cancer overall, and using polytomous logistic regression for associations by tumor behavior and ovarian cancer type. Results: Parity was inversely associated with risk overall and by tumor behavior and type, with a stronger OR (95% CI) for Type I [0.09 (0.04-0.24) for ≥3 full-term births vs. nulliparity] vs. Type II [0.66 (0.43-1.02)] invasive cancers; the OR (95% CI) for borderline tumors was 0.41 (0.22-0.77). Oral contraceptive ever use was not associated with risk overall, but ≥10 years of use vs. never use reduced risk, particularly for invasive cancers. A history of endometriosis was most strongly associated with Type I cancers. Associations with other factors were less clear. Conclusions: These results suggest that associations with some hormone-related factors may differ between borderline and invasive Type I and II ovarian cancers.
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Projected estimates of cancer in Canada in 2020
Article
  • Mar 2020
Background: Cancer projections to the current year help in policy development, planning of programs and allocation of resources. We sought to provide an overview of the expected incidence and mortality of cancer in Canada in 2020 in follow-up to the Canadian Cancer Statistics 2019 report. Methods: We obtained incidence data from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2015). Mortality data (1984-2015) were obtained from the Canadian Vital Statistics - Death Database. All databases are maintained by Statistics Canada. Cancer incidence and mortality counts and age-standardized rates were projected to 2020 for 23 cancer types by sex and geographic region (provinces and territories) for all ages combined. Results: An estimated 225 800 new cancer cases and 83 300 cancer deaths are expected in Canada in 2020. The most commonly diagnosed cancers are expected to be lung overall (29 800), breast in females (27 400) and prostate in males (23 300). Lung cancer is also expected to be the leading cause of cancer death, accounting for 25.5% of all cancer deaths, followed by colorectal (11.6%), pancreatic (6.4%) and breast (6.1%) cancers. Incidence and mortality rates will be generally higher in the eastern provinces than in the western provinces. Interpretation: The number of cancer cases and deaths remains high in Canada and, owing to the growing and aging population, is expected to continue to increase. Although progress has been made in reducing deaths for most major cancers (breast, prostate and lung), there has been limited progress for pancreatic cancer, which is expected to be the third leading cause of cancer death in Canada in 2020. Additional efforts to improve uptake of existing programs, as well as to advance research, prevention, screening and treatment, are needed to address the cancer burden in Canada.
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Body Figure Perceptions and Preferences Among Preadolescent Children
Article
  • Mar 1991
  • INT J EAT DISORDER
A pictorial instrument was developed to examine perceptions of body figure in a cross-sectional survey of 1118 preadolescent children. Hypothesis testing related to differences in figure selections by gender, grade, race, and school/community setting revealed males selected Ideal Self slightly thinner than Self. However, females selected Ideal Self significantly thinner than Self, as well as thinner than males' selection of Ideal Self and Ideal Girl. Additionally, females made thinner Ideal Adult figure selections than males. Though blacks chose heavier figures than whites, females of both races desired thinner figures. Bias toward thinness among females occurred across all levels of age, weight, race, and school/community setting, with 42% desiring thinner figures. Results of this study suggest that the onset of disparate figure perceptions and expectations regarding thinness among females may be evident as early as 6 and 7 years of age.
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Remote Recall of Childhood Height, Weight, and Body Build by Elderly Subjects
Article
  • Aug 1993
  • AM J EPIDEMIOL
The long-term recall of height, weight, and body build was examined as part of a 1988 follow-up of the Boston-based Third Harvard Growth Study (1922-1935). By design, approximately 50 percent of subjects had body mass indices during adolescence of greater than the 75th percentile, and approximately 50 percent of subjects had body mass indices between the 25th and 50th percentiles. Interviewed subjects, aged 71-76 years (n = 181) were asked to recall their high school height and weight and to select outline drawings that best reflected their body size at ages 5, 10, 15, and 20 years. Reports at ages 71-76 years were compared with measurements obtained during childhood and adolescence. High school weight was overestimated by men who were lean as adolescents (mean recalled minus measured difference = 2.5 kg, 95 percent confidence interval 0.78-4.3) and underestimated by women who were obese as adolescents (mean difference = -2.3 kg, 95 percent confidence interval -4.8 to 0.21). Pearson crude correlations between recalled body build and body mass index measured at approximately the same ages were between 0.53 and 0.75 for all ages studied except for a correlation of 0.36 among males at age 5 years. Adjustment for current body mass index only slightly reduced the correlations between adolescent body mass index and recalled build. Adolescent obesity classifications based on indicators derived from recalled weight and build had moderate sensitivities (37-57 percent) and high specificities (98-100 percent). These results indicate that the remote recall of height, weight, and body size can contribute useful information independent of current weight status.
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