Wang Wenjie, Wang Xiaoyan, Jiang Ying, Guo Yingying, Fu Peifen, He Wei, Fu Xiaohua
Department of Nutrition and Food Hygiene, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
Chronic Disease Research Institute, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Br J Cancer. 2025 Feb;132(2):203-211. doi: 10.1038/s41416-024-02906-1. Epub 2024 Nov 28.
Individuals with normal weight obesity (NWO) often escape the attention of healthcare providers who may assume that a normal body mass index (BMI) correlates with low health risks. However, it remains unknown whether NWO increases the risk of breast cancer.
This study included 22,257 and 52,506 pre- and postmenopausal females with normal BMI in the UK Biobank. NWO was defined as participants with a normal BMI (18.5-24.9 kg/m2) and an excess percent body fat (PBF > 33.3%). Cox proportional hazard models were used to investigate the associations of NWO and NWO-related biomarkers with incident breast cancer.
NWO was not associated with premenopausal breast cancer, whereas it was associated with a higher risk of postmenopausal breast cancer (hazard ratio = 1.19, 95% CI: 1.08-1.31). In our meta-analysis, per 5-unit increment in percent body fat level was linked to a 15% (95% CI: 10-19%) elevated risk of postmenopausal breast cancer in females with normal BMI. Stratified analyses showed a stronger positive association in females with higher genetic risk. In our NWO-biomarkers analyses, NWO was linked to 34 identified biomarkers, of which three inflammation markers (monocyte count, neutrophil count, and C-reactive protein), and one ketone body metabolite (β-Hydroxybutyrate) also indicated a positive association with postmenopausal breast cancer.
NWO is associated with an increased risk of postmenopausal breast cancer, indicating that relying solely on BMI neglects the higher risk faced by non-obese postmenopausal women.
体重正常的肥胖个体（NWO）往往会被医疗服务提供者忽视，这些提供者可能认为正常的体重指数（BMI）与低健康风险相关。然而，NWO是否会增加患乳腺癌的风险仍不清楚。
本研究纳入了英国生物银行中22257名绝经前和52506名绝经后BMI正常的女性。NWO被定义为BMI正常（18.5 - 24.9kg/m²）且体脂百分比过高（PBF＞33.3%）的参与者。使用Cox比例风险模型研究NWO及与NWO相关的生物标志物与乳腺癌发病的关联。
NWO与绝经前乳腺癌无关，而与绝经后乳腺癌的较高风险相关（风险比 = 1.19，95%CI：1.08 - 1.31）。在我们的荟萃分析中，BMI正常的女性，体脂百分比每增加5个单位，绝经后乳腺癌风险升高15%（95%CI：10 - 19%）。分层分析显示，在遗传风险较高的女性中存在更强的正相关。在我们对NWO生物标志物的分析中，NWO与34种已确定的生物标志物相关，其中三种炎症标志物（单核细胞计数、中性粒细胞计数和C反应蛋白）以及一种酮体代谢物（β-羟基丁酸）也显示与绝经后乳腺癌呈正相关。
NWO与绝经后乳腺癌风险增加相关，这表明仅依靠BMI会忽视非肥胖绝经后女性面临的较高风险。
