Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population‐based study in Icelandic women

Abstract

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m 2 per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04-1.13), 1.31 (95% CI: 1.18-1.44) and 1.10 (95% CI: 1.00-1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity-cancer relationships.Additional Supporting Information may be found in the online version of this article.

Breast Cancer Population Attributable Risk Proportions Associated with Body Mass Index and Breast Density by Race/Ethnicity and Menopausal Status

“…However, a 2017 meta-analysis by Chen and colleagues showed no association between increased BMI and a premenopausal breast cancer diagnosis (3), and a 2019 systematic literature review and meta-analysis by the World Cancer Research Fund International found an overall inverse association between BMI and a premenopausal breast cancer diagnosis but noted variability across regions; although European studies showed inverse associations, North American studies showed nonsignificant or inverse associations, and Asian studies showed positive associations (8). Studies evaluating the association between premenopausal BMI and future breast cancer (including breast cancers that may occur after the menopausal transition) show mixed results (8)(9)(10)(11).…”

Risk of Colorectal Cancer Associated With Lifetime Excess Weight

“…The findings in our study were consistent with these previous studies when BMI was considered only at a single point of time. However, few studies have evaluated the associations looking at BMI at various points of time during the life span . We considered BMI at various decennial ages and found excess weight at all decennial ages between 20 and 70 years to be associated with CRC risk in a clear dose-response manner.…”

Breast adipose regulation of premenopausal breast epithelial phenotype involves interleukin 10

“…The lower proliferation status of breast glandular epithelial cells of O women may be partly due to cell cycle arrest, leading to cellular senescence. Promotion of senescence has been ascribed to IL10 in a number of cell types (Novakova et al 2010, Huang et al 2018. To examine the possibility that breast adipose-associated IL10 expression is correlated with glandular epithelial cell senescence in the context of the premenopausal breast, we analyzed breast tissues for expression of cell senescence biomarkers TP53, p21, and β-galactosidase (β-GAL) by IHC using specific antibodies to these proteins.…”