Weight management

Among 288,802 UK Biobank participants (mean age 56.2, cancer-free at baseline) followed for a median of 8.2 years, the abbreviated WCRF/AICR adherence score—including body weight, physical activity, diet, and alcohol components—showed the strongest inverse association with uterine cancer of all cancers studied. Each 1-point increment was associated with a 21% risk reduction (HR 0.79; 95% CI 0.73–0.86). This was the largest effect size among nine site-specific cancers with significant associations in multivariable Cox proportional hazards models.

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In this Italian hospital-based case-control study of 454 endometrial cancer cases and 908 age-matched controls (1992-2006), adherence to WCRF/AICR recommendations including BMI management was inversely associated with endometrial cancer risk. Women in the highest versus lowest adherence score quartile had an OR of 0.42 (95% CI 0.30-0.61), representing a 58% risk reduction with a significant trend of decreasing risk with increasing adherence. The protective association was notably stronger among women with normal weight compared to overweight or obese women.

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Among 96,869 Norwegian women in the NOWAC prospective cohort, each one-point increment on the Healthy Lifestyle Index was associated with a 7% lower risk of postmenopausal endometrial cancer (HR 0.93, 95% CI: 0.91–0.95). The HLI incorporated BMI, physical activity, smoking, alcohol, and diet, each scored 0-4 on a 0-20 scale. Cox proportional hazard regression models with multiple imputation confirmed a statistically significant linear inverse association.

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This systematic review assessed the independent and interactive effects of body mass and physical activity on cancer risk across multiple epidemiological studies. Obesity showed a positive association with uterine cancer incidence in women. When the 'fat but fit' hypothesis was tested by evaluating formal interaction terms between body fatness and physical activity, no evidence emerged that high fitness levels attenuate or eliminate the obesity-related uterine cancer risk. The findings support that maintaining a healthy body weight is independently necessary for uterine cancer risk reduction and cannot be substituted by physical activity alone.

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The IARC Handbook Working Group reviewed over 1000 epidemiologic studies and concluded there is sufficient evidence that absence of excess body fatness lowers endometrial cancer risk, specifically for type 1 endometrial cancer. A strong dose-response relationship was identified: relative risks were approximately 1.5 for overweight (BMI 25.0–29.9), 2.5 for class 1 obesity (BMI 30.0–34.9), 4.5 for class 2 obesity (BMI 35.0–39.9), and 7.1 (95% CI, 6.3–8.1) for class 3 obesity (BMI ≥40.0) compared to normal BMI. Among women receiving hormone-replacement therapy, the strength of association with excess body fatness was reduced. An estimated 4.5 million deaths worldwide in 2013 were caused by overweight and obesity, with the obesity-related cancer burden representing up to 9% of the total cancer burden among women in North America, Europe, and the Middle East.

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In the Swedish cohort of ~60,000 women, the cadmium-endometrial cancer association was stronger among lean and normal-weight women (52% increased risk in the highest cadmium tertile) compared to the overall population (39% increase). Never-smoking women with normal BMI and no exogenous estrogen exposure who had consistently high dietary cadmium over 10 years showed a 2.9-fold increased endometrial cancer risk. This pattern suggests that in women with lower overall estrogenic load (normal BMI, no hormone replacement), cadmium's estrogen-mimicking effects become more pronounced, making weight management relevant to modifying this risk pathway.

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