School of Public Health, University of California, Berkeley, California.
Unit of Cancer Epidemiology Città della Salute e della Scienza University-Hospital, Turin, Italy.
Cancer Epidemiol Biomarkers Prev. 2023 Sep 1;32(9):1217-1226. doi: 10.1158/1055-9965.EPI-23-0231.
The higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood.
We performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately.
Sixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways.
Adduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males.
Only two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.
非霍奇金淋巴瘤（NHL）在男性中的发病率较高，但目前尚不清楚其原因。尽管活性氧（ROS）已被认为是 NHL 的病因之一，但它们不能直接在存档的血液中测量。
我们对来自欧洲前瞻性癌症与营养研究-意大利队列的 67 例 NHL 病例和 82 例匹配对照者的人血清白蛋白（HSA）中的稳定 ROS 加合物进行了非靶向的加合物组学分析。回归和分类方法用于选择与所有受试者以及男性和女性中 NHL 相关的特征。
通过液相色谱-高分辨率质谱法在 Cys34（n = 55）和 Lys525（n = 12）处定量了 67 个 HSA-加合物特征。在所有受试者中，有三个特征与 NHL 相关，而在男性和女性中分别有七个和五个特征与 NHL 相关，且重叠最小。两个选定的特征在病例中更为丰富，七个特征在对照中更为丰富，这表明 ROS 平衡的改变可能会影响 NHL 的发病率。热图显示了特征在性别之间的差异聚类，这表明了作用途径的差异。
以 Cys34 氧化产物和二硫化物为主的加合物簇进一步表明 ROS 和氧化还原生物学在 NHL 的病因学中起作用。饮食和酒精消耗方面的性别差异也有助于解释男女之间特征选择的有限重叠。有趣的是，一种来自肠道微生物代谢的甲硫醚二硫化物在男性病例中更为丰富，这表明微生物易位可能是男性 NHL 的一个潜在致病因素。
与 NHL 相关的 ROS 加合物中只有两个在性别之间重叠，一个加合物暗示微生物易位是 NHL 的一个危险因素。
