Li Xu, Hao Yu, Wu Xue-Yao, Zhao Xun-Ying, Diao Sha, Zhang Xiao-Fan, Tian Lu-Lu, Ye Feng, Li Jia-Yuan
Department of Epidemiology and Health Statictics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2023 May;54(3):579-584. doi: 10.12182/20230560506.
To explore the potential interactions among obesity-related proteins in the pathogenic process of breast cancer (BC) in women.
We conducted a case-control study, enrolling 279 primary breast cancer cases and 260 age-frequency-matched healthy women between April 2014 and May 2015. Based on the evidence of previous published literature on obesity-related proteins and BC risks, we selected proteins that received more attention and measured the plasma levels of these proteins by enzyme-linked immunosorbent assay (ELISA). After stratification of the subjects according to their menopausal status, an analytic strategy combining multivariate logistic regression and generalized multifactor dimensionality reduction (GMDR) was used to explore the effect of the possible interactions of these proteins on BC risk.
There were marginal high-order interactions among insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), C-reactive protein (CRP), resistin (RETN), soluble leptin receptor (sOB-R), and adiponectin (ADP) in premenopausal women (with the balanced accuracy for the testing set being 59.01%, cross-validation consistency being 10/10, and permutation test =0.05). There were high-order interactions among leptin (LEP), sOB-R, ADP, CRP, IGFBP3 and visfatin (VF) in postmenopausal women (with the balanced accuracy for the testing set being 67.31%, cross-validation consistency being 10/10, and permutation test =0.01). Along with an increase in the number of obesity-related proteins to which the subjects were exposed, the risk of developing breast cancer gradually increased in both pre- and postmenopausal women ( =2.18, 95% : 1.69-2.82; =2.41, 95% : 1.75-3.32).
This preliminary study suggested high-order interactions among obesity-related proteins on BC risk in both pre- and postmenopausal women. In future studies, close attention should be given to these potential interactions when these proteins are used jointly as predictors, as well as in developing a comprehensive risk scoring system for BC.
探讨肥胖相关蛋白在女性乳腺癌（BC）发病过程中的潜在相互作用。
我们开展了一项病例对照研究，在2014年4月至2015年5月期间招募了279例原发性乳腺癌病例和260例年龄频率匹配的健康女性。基于先前发表的关于肥胖相关蛋白与BC风险的文献证据，我们选择了受到更多关注的蛋白，并通过酶联免疫吸附测定（ELISA）测量这些蛋白的血浆水平。在根据绝经状态对受试者进行分层后，采用多变量逻辑回归和广义多因素降维（GMDR）相结合的分析策略，探讨这些蛋白的可能相互作用对BC风险的影响。
绝经前女性中，胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）、C反应蛋白（CRP）、抵抗素（RETN）、可溶性瘦素受体（sOB-R）和脂联素（ADP）之间存在边缘高阶相互作用（测试集的平衡准确率为59.01%，交叉验证一致性为10/10，置换检验=0.05）。绝经后女性中，瘦素（LEP）、sOB-R、ADP、CRP、IGFBP3和内脂素（VF）之间存在高阶相互作用（测试集的平衡准确率为67.31%，交叉验证一致性为10/10，置换检验=0.01）。随着受试者暴露于肥胖相关蛋白数量的增加，绝经前和绝经后女性患乳腺癌的风险均逐渐增加（比值比=\(2.18\)，95%置信区间：1.69 - 2.82；比值比=\(2.41\)，95%置信区间：1.75 - 3.32）。
这项初步研究表明，肥胖相关蛋白在绝经前和绝经后女性的BC风险上存在高阶相互作用。在未来的研究中，当联合使用这些蛋白作为预测指标以及开发BC综合风险评分系统时，应密切关注这些潜在的相互作用。
