Background 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. Methods Physical activity levels were assessed using doubly labeled water, accelerometers, and 24-hr recalls in the IDATA study (N = 707 participants, ages 50-74 years, 51% women), with 1-6 assessments over 12 months and two 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. Results 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, ten of which supported a protective role of physical activity. Notably, higher physical activity was associated with lower 16alpha-hydroxy DHEA 3-sulfate (androgen) and adipoylcarnitine (fatty acid), both of which were associated with increased breast cancer risk (OR per 1 standard deviation (SD)=1.34, 95% CI = 1.16-1.55 and 1.26,1.11-1.42, 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 (0.82,0.73-0.93). Conclusion 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.

中文翻译：

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身体活动、代谢物和乳腺癌相关性


背景 通常的体育活动对生理和疾病预防的影响尚不完全清楚。我们检查了身体活动、代谢物和乳腺癌风险之间的关联。方法 在 IDATA 研究中，使用双标记水、加速度计和 24 小时召回评估身体活动水平 （N = 707 名参与者，年龄 50-74 岁，51% 为女性），在 12 个月内进行 1-6 次评估和两次血样采集。部分 Spearman 相关性用于估计体力活动与 843 种血清代谢物之间的关联，并针对多项测试进行了校正。在一项嵌套病例对照研究 （621 例，621 例对照） 中，使用条件 logistic 回归模型估计绝经后乳腺癌代谢物的比值比 （ORs） 和 95% 置信区间 （CIs），所有统计检验均为 2 侧。结果 体力活动与跨越多种途径的 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有关，其中 10 种支持身体活动的保护作用。值得注意的是，较高的体力活动与 16α-羟基 DHEA 3-硫酸盐（雄激素）和脂酰肉碱（脂肪酸）的降低有关，这两者都与乳腺癌风险增加有关（每 1 个标准差 （SD）=1.34,95% CI = 1.16-1.55 和 1.26,1.11-1.42）。较高的体力活动能量消耗也与较低的鞘磷脂 （d18：1/20：1， d18：2/20：0） 相关，这与降低乳腺癌风险相关 （0.82,0.73-0.93）。结论 身体活动与广泛的代谢物有关，其中许多代谢物与对乳腺癌的保护作用一致。 我们的研究结果强调了预防癌症的潜在代谢途径。