Associations of life course obesity with endometrial cancer in the Epidemiology of Endometrial Cancer Consortium (E2C2)

Abstract

Background Adult obesity is a strong risk factor for endometrial cancer (EC); however, associations of early life obesity with EC are inconclusive. We evaluated associations of young adulthood (18–21 years) and adulthood (at enrolment) body mass index (BMI) and weight change with EC risk in the Epidemiology of Endometrial Cancer Consortium (E2C2). Methods We pooled data from nine case-control and 11 cohort studies in E2C2. We performed multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for BMI (kg/m2) in young adulthood and adulthood, with adjustment for BMI in adulthood and young adulthood, respectively. We evaluated categorical changes in weight (5-kg increments) and BMI from young adulthood to adulthood, and stratified analyses by histology, menopausal status, race and ethnicity, hormone replacement therapy (HRT) use and diabetes. Results We included 14 859 cases and 40 859 controls. Obesity in adulthood (OR = 2.85, 95% CI = 2.47–3.29) and young adulthood (OR = 1.26, 95% CI = 1.06–1.50) were positively associated with EC risk. Weight gain and BMI gain were positively associated with EC; weight loss was inversely associated with EC. Young adulthood obesity was more strongly associated with EC among cases diagnosed with endometrioid histology, those who were pre/perimenopausal, non-Hispanic White and non-Hispanic Black, among never HRT users and non-diabetics. Conclusions Young adulthood obesity is associated with EC risk, even after accounting for BMI in adulthood. Weight gain is also associated with EC risk, whereas weight loss is inversely associated. Achieving and maintaining a healthy weight over the life course is important for EC prevention efforts.

The Effectiveness of Metabolic Bariatric Surgery in Preventing Gynecologic Cancer - from Pathophysiology to Clinical Outcomes

“…Importantly, BMI was associated with increased all-cause and endometrial cancer-specific mortality, particularly in the group of those suffering from severe obesity (pEE = 2.06 (95% CI 1.55-2.74) 95 . Another recent meta-analysis of 11 cohort studies by the Epidemiology of Endometrial Cancer Consortium, with 14,859 case and 40,895 controls, found a positive correlation of obesity in adulthood (OR 2.85, 95% CI 2.47-3.29) and early adulthood (OR 1.26, 95% CI 1.06-1.50) with the risk of endometrial cancer 96 . These outcomes seem to be generally universal across different ethnic groups, regarding both clinical metrics (BMI, waist circumference) and endometrial cancer-related biomarkers (IGF-1, leptin, adiponectin, IL-1, IL-6) 89 , 97 - 100 .…”

Endometrial Cancer: Updates in Molecular Characterization and Treatment Opportunities

“…6 A possible rationale for the increase is the higher prevalence of certain risk factors among women (e.g., obesity, alcohol use, shifting reproductive trends, age, nulliparity, oral contraception, hormone replacement therapy and genetic factors such as Lynch syndrome). 1,[7][8][9] Preventative factors against EC include exercise, weight loss, pregnancy and diet (e.g., soy, coffee and tea intake) and are all associated with an inverse risk towards EC. 10 Historically, clinicopathological features (e.g., cancer stage, histologic grade, tumor subtype [endometrioid, serous, clear cell, mixed cell adenocarcinoma and other rare subtypes] and histopathologic markers) have been used for risk stratification of disease status in patients with EC.…”

Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities

“…7–9 Many studies have shown that its growing incidence is mainly connected with obesity. 10–13 In addition, it is associated with an aging population, type II diabetes, metabolic factors, genetic factors, reproductive factors, and the use of tamoxifen. 14 At present, patients with early-stage disease are mainly treated with surgery, which includes total hysterectomy and bilateral salpingo-oophorectomy, 14 and patients with moderate/high risk of recurrence and inoperable cases highly depend on external radiation, chemotherapy, or a combination of treatments (Fig.…”