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

Mohammad L. Rahman, Bryan A. Bassig, Hasmik Grigoryan, Wei Hu, H. Dean Hosgood, Wen Yi Huang, Jason Y.Y. Wong, Paul Strickland, Stephen M. Rappaport, Qing Lan, Nathaniel Rothman

Research output: Contribution to journalArticlepeer-review

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 between circulatory albumin adducts and acute myeloid leukemia (AML), the most common adult myeloid leukemia that showed consistent associations with environmental exposures. We conducted a nested case-control study of 52 incident AML cases and 103 controls matched on age, sex and race within two prospective cohorts: the CLUE and PLCO studies. We measured 42 untargeted albumin adducts in prediagnostic 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 the 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 =.01). These associations were largely driven by effects present among cases diagnosed at or above the median follow-up time of 5.5 years. In conclusion, applying a novel approach to characterize exposures in the prediagnostic samples, we found evidence supporting the notion that oxidative stress may play a role in the pathogenesis of AML. Our findings offer insight into AML etiology and may be relevant in identifying novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalInternational Journal of Cancer
Volume153
Issue number3
DOIs
StatePublished - Aug 1 2023

Keywords

  • acute myeloid leukemia
  • adductomics
  • glutathione
  • oxidative stress
  • γ-glutamylcysteine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'A nested case-control study of untargeted albumin adductomics and acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this