A nested case-control study of untargeted albumin adductomics and acute myeloid leukemia

Abstract Environmental exposures often produce reactive electrophiles in vivo, leading to oxidative stress, which plays a major role in carcinogenesis. These electrophiles frequently form adducts with human albumin, which can be measured to assess in vivo oxidative stress. Here, we aimed to examine the associations of albumin adducts with acute myeloid leukemia (AML), the most common adult myeloid leukemia with consistent associations with environmental exposures. We conducted a case-control study of 52 incident AML cases and 103 controls matched on age, sex, and race nested on two prospective cohorts: the CLUE and PLCO studies. We measured 42 untargeted albumin adducts in pre-diagnostic samples using liquid chromatography-high resolution mass spectrometry. Circulatory albumin adducts were associated with AML in conditional logistic regression models. For instance, higher levels of Cys34 disulfide adduct of the S-γ-glutamylcysteine, a precursor of an essential antioxidant, glutathione were associated with a lower risk of AML (odds ratios (95% confidence intervals) for the 1st, 2nd, and 3rd tertiles were 1.0, 0.65(0.31–1.36); and 0.31(0.12–0.80), respectively (p-trend = 0.01). These associations were largely driven by effects present among cases diagnosed ≥ median follow-up year of 5.5 years. Our results support the idea that oxidative stress may play a role in the etiology of AML.