Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2)

Talar S Habeshian & Veronica Wendy Setiawan et al.

Abstract

Background:

The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors.

Methods:

We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors.

Results:

Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09–1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case–control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy.

Conclusions:

Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association.

Impact:

This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

Funding

NCI NIH HHS

HHSN261201800032C

NCI NIH HHS

P30 CA016087

NCI NIH HHS

P01 CA087969

NCI NIH HHS

U01 CA164974

NCI NIH HHS

U01 CA250476

NCI NIH HHS

HHSN261201800015I

NCI NIH HHS

R01 CA105212

NCI NIH HHS

R01 CA047749

NCI NIH HHS

P01 CA033619

NCI NIH HHS

R01 CA081212

NCI NIH HHS

HHSN261201800032I

NCI NIH HHS

P30 CA033572

National Cancer Institute (NCI)

U01CA164973

NICHD NIH HHS

N01 HD023166

NCI NIH HHS

U01 CA164973

NCI NIH HHS

R03 CA169888

NCI NIH HHS

HHSN261201800009I

NCI NIH HHS

U01 CA199277

NCI NIH HHS

UM1 CA164917

NCI NIH HHS

HHSN261201800009C

NCI NIH HHS

K05 CA092002

NCI NIH HHS

R01 CA087538

NCI NIH HHS

P30 CA016056

NCCDPHP CDC HHS

NU58DP006344

NCI NIH HHS

U01 CA182934

NCI NIH HHS

R01 CA058598

NIEHS NIH HHS

P30 ES000260

NCI NIH HHS

R01 CA092585

NCI NIH HHS

R01 CA082838

NCI NIH HHS

P30 CA008748

Intramural NIH HHS

ZIA CP010126

NCI NIH HHS

R01 CA039742

NCI NIH HHS

R01 CA083918

NCI NIH HHS

P30 CA023100

NCI NIH HHS

R01 CA098346

NCI NIH HHS

R01 CA077398

NCI NIH HHS

HHSN261201800015C

NCI NIH HHS

U01 CA202979

National Cancer Institute

U01CA164973