Abstract LB-184: Risk factors for lung cancer among survivors of non-Hodgkin lymphoma
Authors: Lam Clara , Curtis Rochelle , Dores Graca , Engels Eric , Caporaso Neil , Polliack Aaron , Warren Joan , Young Heather , Levine Paul , Elmi Angelo , Fraumeni Joseph , Tucker Margaret , Morton Lindsay 
Published: August 2015

Abstract
Background: Previous studies have reported that non-Hodgkin lymphoma (NHL) survivors have increased risk of developing lung cancer; however, risks associated with specific treatments and immune-related risk factors have not been quantified.
Methods: We assessed second lung cancer risk among 44,870 1-year survivors of first primary NHL diagnosed at ages 66-84 years during 1992-2009 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data linkage. Information on potential risk factors, including NHL treatments, infections, and immune-related medical conditions, was derived from Medicare claims.
Results: A total of 700 second lung cancers were diagnosed among NHL survivors, including 259 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 127 after follicular lymphoma (FL), 116 after diffuse large B-cell lymphoma (DLBCL), and 137 after other NHL subtypes. Lung cancer risks were significantly increased among CLL/SLL survivors who received fludarabine-containing chemotherapy without rituximab (Cox regression hazard ratio [HR] = 2.28, 95% confidence interval [CI] = 1.48-3.52). Elevated risks were also seen among DLBCL survivors who received cyclophosphamide-containing chemotherapy (without rituximab HR = 2.13, 95%CI = 1.01-4.47; with rituximab HR = 1.82, 95%CI = 0.87-3.80). After adjusting for history of smoking, lower airway respiratory infections, particularly pneumonia, were associated with increased risks of second lung cancer after CLL/SLL (HR = 2.21, 95%CI = 1.65-2.96), DLBCL (HR = 1.90, 95%CI = 1.26-2.87), and FL (HR = 1.98, 95%CI = 1.31-3.00). The pattern of lung cancer risks associated with autoimmune conditions was complex, with increased risks seen for B-cell activating autoimmune conditions among DLBCL survivors (HR = 1.63, 95%CI = 1.00-2.66) and T-cell activating autoimmune conditions among survivors of other NHL subtypes (HR = 1.56, 95%CI = 1.07-2.27). In contrast, T-cell activating autoimmune conditions were significantly inversely associated with lung cancer among FL survivors (HR = 0.57, 95%CI = 0.34-0.96), and no associations with autoimmune disease were identified among CLL/SLL survivors.
Conclusion: We report for the first time that chemotherapy used in treatment of NHL, infections, and autoimmune diseases are associated with the risk of developing lung cancer after NHL. Further research is needed to confirm the observed associations and understand the underlying carcinogenic mechanisms.
Citation Format: Clara Lam, Rochelle Curtis, Graca Dores, Eric Engels, Neil Caporaso, Aaron Polliack, Joan Warren, Heather Young, Paul Levine, Angelo Elmi, Joseph Fraumeni, Margaret Tucker, Lindsay Morton. Risk factors for lung cancer among survivors of non-Hodgkin lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-184. doi:10.1158/1538-7445.AM2015-LB-184