Lv Yangbo, Mao Weili, Jin Hangbiao, Qu Jianli, He Dongjuan
Department of Colorectal Surgery, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, PR China.
Department of Pharmacy, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, PR China.
Environ Pollut. 2025 May 15;373:126114. doi: 10.1016/j.envpol.2025.126114. Epub 2025 Mar 24.
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidation product, 6PPD-quinone (6PPDQ), are widely present in the environment. Toxicological studies have demonstrated that they can induce adverse health effects on the intestinal system. However, epidemiological studies examining the association between human 6PPD and 6PPDQ exposure and colorectal cancer (CRC) risk remain scarce. In this study, human urinary 6PPD and 6PPDQ concentrations were analyzed in 329 controls and 367 CRC cases from Quzhou, China. A combination of analyses, including unconditional logistic regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline analysis, was employed to evaluate associations between urinary 6PPD and 6PPDQ levels and CRC risk, adjusting for demographic and lifestyle variables. The median concentration of 6PPDQ in CRC cases (0.94 vs 0.14 μg/g creatinine) was significantly higher than that in controls (Mann-Whitney U test, p = 0.001), while the median concentration of 6PPD showed no significant (p = 0.061) difference between the two groups (0.31 vs 0.38 μg/g creatinine). Higher urinary 6PPDQ concentrations were significantly associated with increased CRC risk, especially among participants with third (adjusted OR = 2.79, 95 % CI: 1.76-4.47; p for trend <0.001) and fourth (adjusted OR = 7.13, 95 % CI: 4.31-12.0; p for trend <0.001) quartiles of exposure. Additionally, the joint effects of 6PPD and 6PPDQ exposure, assessed using the BKMR model, indicated a positive association with CRC risk, suggesting a cumulative risk from co-exposure. This study provides the first epidemiological evidence linking human 6PPDQ exposure to CRC risk, highlighting its potential role in colorectal carcinogenesis.
N-（1,3-二甲基丁基）-N'-苯基-对苯二胺（6PPD）及其氧化产物6PPD-醌（6PPDQ）广泛存在于环境中。毒理学研究表明，它们可对肠道系统产生不良健康影响。然而，关于人类6PPD和6PPDQ暴露与结直肠癌（CRC）风险之间关联的流行病学研究仍然很少。在本研究中，分析了来自中国衢州的329名对照和367例CRC病例的人尿6PPD和6PPDQ浓度。采用包括无条件逻辑回归、贝叶斯核机器回归（BKMR）和受限立方样条分析在内的综合分析方法，评估尿6PPD和6PPDQ水平与CRC风险之间的关联，并对人口统计学和生活方式变量进行了调整。CRC病例中6PPDQ的中位数浓度（0.94 vs 0.14μg/g肌酐）显著高于对照组（曼-惠特尼U检验，p = 0.001），而6PPD的中位数浓度在两组之间无显著差异（p = 0.061）（0.31 vs 0.38μg/g肌酐）。尿6PPDQ浓度较高与CRC风险增加显著相关，尤其是在暴露于第三（调整后的OR = 2.79，95%CI：1.76 - 4.47；趋势p < 0.001）和第四（调整后的OR = 7.13，95%CI：4.31 - 12.0；趋势p < 0.001）四分位数的参与者中。此外，使用BKMR模型评估的6PPD和6PPDQ联合暴露效应表明与CRC风险呈正相关，提示共同暴露存在累积风险。本研究提供了首个将人类6PPDQ暴露与CRC风险联系起来的流行病学证据，突出了其在结直肠癌发生中的潜在作用。
