Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the aetiology of non-Hodgkin lymphoma

Nilesh W. Gaikwada, Li Yangb, Dennis D. Weisenburgerc, Julie Vosed, Cheryl Beseler, Eleanor G. Rogan & Ercole L. Cavalieri*aa Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USAb Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USAc Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USAd Oncology & Hematology Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USAe Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USAAddress for Correspondence: Ercole Cavalieri, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA. Tel.: 402-559-7237. Fax: 402-559-8068. E-mail: ecavalie@unmc.eduA variety of evidence suggests that estrogens may induce non-Hodgkin lymphoma (NHL). The reaction of catechol estrogen quinones with DNA to form depurinating estrogen-DNA adducts is hypothesized to initiate this process. These adducts are released from DNA, shed from cells into the bloodstream and excreted in urine. The aim of this study was to determine whether or not the depurinating estrogen-DNA adducts might be involved in the aetiology of human NHL. Estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified in spot urine samples from 15 men with NHL and 30 healthy control men by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of estrogen-DNA adducts were significantly higher in the men with NHL than in the healthy control men. Thus, formation of estrogen-DNA adducts may play a critical role in the aetiology of NHL, and these adducts could be potential biomarkers of NHL risk.