Watts Eleanor L, Moore Steven C, Abar Leila, Hong Hyokyoung G, Saint-Maurice Pedro F, O'Connell Caitlin, Matthews Charles E, Loftfield Erikka
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Breast Cancer Unit, Champalimaud Foundation, Lisbon, Portugal.
J Natl Cancer Inst. 2025 Feb 1;117(2):355-365. doi: 10.1093/jnci/djae246.
The effects of usual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites, and breast cancer risk.
Physical activity levels were assessed using doubly labeled water, accelerometers, and 24-hour recalls in the Interactive Diet and Activity Tracking in AARP (IDATA) Study (N = 707 participants, ages 50-74 years, 51% women), with 1 to 6 assessments over 12 months and 2 blood sample collections. Partial Spearman correlations were used to estimate associations between physical activity and 843 serum metabolites, corrected for multiple testing. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolites with postmenopausal breast cancer in a nested case-control study (621 cases, 621 controls); all statistical tests were 2-sided.
Physical activity was associated with 164 metabolites spanning numerous pathways, including amino acid and fatty acid metabolism. Twelve of these metabolites were also associated with breast cancer risk, 10 of which supported a protective role of physical activity. Notably, higher physical activity was associated with lower 16alpha-hydroxy dehydroepiandrosterone 3-sulfate (sulfated steroid) and adipoylcarnitine (fatty acid), both of which were associated with increased breast cancer risk (OR per 1 standard deviation [SD] = 1.34, 95% CI = 1.16 to 1.55 and 1.26, 1.11 to 1.42, respectively). Higher physical activity energy expenditure was also associated with lower sphingomyelin (d18:1/20:1, d18:2/20:0), which was associated with a reduced breast cancer risk (OR = 0.82, 95% CI = 0.73 to 0.93).
Physical activity is associated with a broad range of metabolites, many of which are consistent with a protective effect against breast cancer. Our findings highlight potential metabolic pathways for cancer prevention.
日常身体活动对生理和疾病预防的影响尚未完全明确。我们研究了身体活动、代谢物与乳腺癌风险之间的关联。
在AARP互动饮食与活动追踪研究（IDATA）中，采用双标水法、加速度计和24小时回顾法评估身体活动水平（N = 707名参与者，年龄50 - 74岁，51%为女性），在12个月内进行1至6次评估，并采集2次血样。采用偏斯皮尔曼相关性分析估计身体活动与843种血清代谢物之间的关联，并对多重检验进行校正。在一项巢式病例对照研究（621例病例，621例对照）中，使用条件逻辑回归模型估计代谢物与绝经后乳腺癌的比值比（OR）和95%置信区间（CI）；所有统计检验均为双侧检验。
身体活动与涉及众多途径的164种代谢物相关，包括氨基酸和脂肪酸代谢。其中12种代谢物也与乳腺癌风险相关，其中10种支持身体活动的保护作用。值得注意的是，较高的身体活动水平与较低的16α - 羟基硫酸脱氢表雄酮（硫酸化类固醇）和己二酰肉碱（脂肪酸）相关，这两种物质均与乳腺癌风险增加相关（每1个标准差[SD]的OR分别为1.34，95%CI = 1.16至1.55和1.26，1.11至1.42）。较高的身体活动能量消耗也与较低的鞘磷脂（d18:1/20:1，d18:2/20:0）相关，其与降低的乳腺癌风险相关（OR = 0.82，95%CI = 0.73至0.93）。
身体活动与多种代谢物相关，其中许多与对乳腺癌的保护作用一致。我们的研究结果突出了癌症预防的潜在代谢途径。
