What is the clinical evidence from this study?

Study design: Cohort. Population: Obesity-related cancer (n=37540). Intervention: Obesity with and without cardiometabolic risk factors vs. Women without obesity and without risk factors. Primary outcome: Incident obesity-related cancers (HR 1.42, 95% CI 1.29-1.56).

April 19, 2026

Abstract LB210: Obesity with and without cardiometabolic risk factors, biomarkers, and incident obesity-related cancer: The Women’s Health Study

Key Result

Obesity increased the risk of incident obesity-related cancers both without (HR 1.28; 95% CI 1.06-1.54) and with ≥1 cardiometabolic risk factor (HR 1.42; 95% CI 1.29-1.56).

Key Points

The aim is to explore the role of obesity-related cardiometabolic risk factors and biomarkers on the risk of obesity-related cancers in women.
Classified 37,540 women by obesity and cardiometabolic risk factors based on BMI and health questionnaires.
Measured baseline blood biomarkers in 27,210 participants.
Applied Cox proportional hazards regression models to assess cancer risks adjusted for various factors.
Followed participants for a median of 22 years to identify incident obesity-related cancers.
Confirmed 4,895 incident obesity-related cancers.
Higher risks found in women with obesity: HR=1.28 without risk factors and HR=1.42 with risk factors.
Endometrial cancer showed the strongest association with existing risk factors (HR=3.58).
Elevated inflammation, glycemia, and dyslipidemia related to higher cancer risks (HRs 1.15-1.38).

Study Design

Type

Cohort (n=37,540)

Structured PICO

Does obesity with or without cardiometabolic risk factors increase the risk of incident obesity-related cancer in women?

Population

37,540 Women's Health Study participants, baseline mean age 54.6 years. 19% of women had obesity. Baseline blood biomarkers were measured in 27,210 women.

Intervention

Obesity (body mass index [BMI] ≥30 kg/m2) with or without any cardiometabolic risk factors (type 2 diabetes, high cholesterol, and hypertension)

Comparator

Women without obesity and without cardiometabolic risk factors

Outcome

Incident obesity-related cancers over a median follow-up of 22 yearshard clinical

Obesity is associated with an increased risk of several obesity-related cancers regardless of the presence of cardiometabolic risk factors, though poor cardiometabolic health may further mediate this risk.

Main Result

Effect estimate: HR 1.42 (95% CI 1.29-1.56)

Abstract

Abstract Obesity is an established risk factor for at least 13 types of cancers, yet the role of obesity-related cardiometabolic risk factors and biomarkers in mediating this relationship remains unclear. We classified 37, 540 Women’s Health Study participants as obese (body mass index BMI≥30 kg/m2) or non-obese and with or without any cardiometabolic risk factors (type 2 diabetes, high cholesterol, and hypertension), with status updated annually via questionnaire. Baseline blood biomarkers were measured in 27, 210 women. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risk of obesity-related cancers, adjusting for age, reproductive history, hormone therapy use, lifestyles, and cancer site-specific factors. The reference group in all models is women without obesity and without risk factors. Baseline mean age was 54. 6 years, 19% of women had obesity, and ≥1 cardiometabolic risk factor was present in 65% of women who had obesity and 42% of those without obesity. We confirmed 4, 895 incident obesity-related cancers over a median follow-up of 22 years. The obesity-related cancer risk was elevated among women with obesity without risk factors (HR=1. 28; 95% CI=1. 06, 1. 54) and with ≥1 risk factor (HR=1. 42; 95% CI=1. 29, 1. 56). Strongest association for obesity with risk factors was observed for endometrial cancer (585 cases; HR=3. 58; 95% CI=2. 70, 4. 76), followed by kidney (139 cases; HR=1. 97; 95% CI=1. 10, 5. 53), colorectal (626 cases; HR=1. 69; 95% CI=1. 27, 2. 25) and postmenopausal breast cancer (2, 765 cases; HR=1. 22; 95% CI=1. 08, 1. 39) ; no association was observed for ovarian cancer (280 cases; HR=0. 90; 95% CI=0. 58, 1. 38). Obesity without risk factors was associated with an elevated risk of pancreatic (139 cases; HR=3. 93; 95% CI=1. 65, 9. 39) and endometrial cancer (HR=2. 20; 95% CI=1. 37, 3. 54). Higher obesity-related cancer risk was observed among women with obesity and elevated inflammation (C-reactive protein, soluble intercellular adhesion molecule-1, fibrinogen, and GlycA), glycemia (hemoglobin A1c), and dyslipidemia (ApoB/A1 ratio, cholesterol, high-density lipoprotein, low-density lipoprotein, and lipoprotein (a) ) (HRs 1. 15-1. 38). Obesity with normal levels of inflammation, glycemia, and kidney function (creatinine and homocysteine) biomarkers was also related to a higher obesity-related cancer risk (HRs 1. 08-1. 38). In conclusion, obesity with and without cardiometabolic risk factors is positively associated with risk of several obesity-related cancers. Poor cardiometabolic health, glycemic and lipid metabolism, and inflammation may mediate obesity’s association with cancer, although excess cancer risk persists among metabolically healthier women with obesity. Citation Format: Cong Wang, Howard D. Sesso, Paulette D. Chandler, Aditi Hazra, Samia Mora, I-Min Lee, Julie E. Buring, JoAnn E. Manson, Deirdre K. Tobias. Obesity with and without cardiometabolic risk factors, biomarkers, and incident obesity-related cancer: The Women’s Health Study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr LB210.

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