Autoimmune Disease and Risk of Lymphoma: Analysis from Real-world Data and Mendelian Randomization Study

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2025 Feb 25

PMID 40000981

Authors

Linquan Zhan

Siyuan Chen

Yingyue Liu

Tiange Lu

Zhuoya Yu

Xin Wang

Xiangxiang Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Autoimmune diseases (AIDs) appear to be the primary predisposing factors for lymphoma. This study aims to investigate the causal effects between AIDs and lymphomagenesis.

Methods: A two-sample Mendelian randomization (MR) framework was employed to estimate the causal effect through UK Biobank (UKB) and FinnGen cohorts. Patients with histories of AIDs and diagnosed with lymphoma were enrolled in real-world studies.

Results: MR analysis investigated the potential causal effect of AIDs on the risks of lymphoma [odd ratio (OR) = 1.001, 95% confidence interval (CI) = 1.000-1.002, p = 0.040]. In our real-world data, there are no significantly increased risks for lymphoma when analyzing ORs for the history of rheumatoid arthritis (RA) and psoriasis (PsO) (OR 1.027, 95% CI = 0.516-2.04 for RA, and OR 1.022, 95% CI = 0.442-2.365 for PsO). The serum albumin (ALB) and sialic acid (SA) levels were independent prognostic factors for both progression-free survival (PFS) and overall survival (OS) in AIDs-associated lymphoma (AAL) patients.

Conclusions: Our results confirmed the causal relationships between AIDs and risks of lymphoma. Serum ALB and SA levels have demonstrated a vital influence on outcomes of AAL patients, in which the IL-17 pathway might play an active role.

References

Royer B, Cazals-Hatem D, Sibilia J, Agbalika F, Cayuela J, Soussi T . Lymphomas in patients with Sjogren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood. 1997; 90(2):766-75. View

Smedby K, Vajdic C, Falster M, Engels E, Martinez-Maza O, Turner J . Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood. 2008; 111(8):4029-38. PMC: 2288717. DOI: 10.1182/blood-2007-10-119974. View

Rosenblum M, Remedios K, Abbas A . Mechanisms of human autoimmunity. J Clin Invest. 2015; 125(6):2228-33. PMC: 4518692. DOI: 10.1172/JCI78088. View

Ji J, Liu X, Sundquist K, Sundquist J . Survival of cancer in patients with rheumatoid arthritis: a follow-up study in Sweden of patients hospitalized with rheumatoid arthritis 1 year before diagnosis of cancer. Rheumatology (Oxford). 2011; 50(8):1513-8. DOI: 10.1093/rheumatology/ker143. View

Bernatsky S, Ramsey-Goldman R, Isenberg D, Rahman A, Dooley M, Sibley J . Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 2007; 46(5):830-2. DOI: 10.1093/rheumatology/kel444. View

Rouvier E, Luciani M, Mattei M, Denizot F, Golstein P . CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993; 150(12):5445-56. View

Hollander P, Rostgaard K, Smedby K, Chang E, Amini R, de Nully Brown P . Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma. Am J Epidemiol. 2015; 182(7):624-32. PMC: 4581588. DOI: 10.1093/aje/kwv081. View

Smedby K, Baecklund E, Askling J . Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics. Cancer Epidemiol Biomarkers Prev. 2006; 15(11):2069-77. DOI: 10.1158/1055-9965.EPI-06-0300. View

Johnsen S, Brun J, Goransson L, Smastuen M, Johannesen T, Haldorsen K . Risk of non-Hodgkin's lymphoma in primary Sjögren's syndrome: a population-based study. Arthritis Care Res (Hoboken). 2012; 65(5):816-21. DOI: 10.1002/acr.21887. View

10.

Smedby K, Hjalgrim H, Askling J, Chang E, Gregersen H, Porwit-MacDonald A . Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst. 2006; 98(1):51-60. DOI: 10.1093/jnci/djj004. View

11.

Kleinstern G, Maurer M, Liebow M, Habermann T, Koff J, Allmer C . History of autoimmune conditions and lymphoma prognosis. Blood Cancer J. 2018; 8(8):73. PMC: 6070501. DOI: 10.1038/s41408-018-0105-4. View

12.

Wang S, Vajdic C, Linet M, Slager S, Voutsinas J, Nieters A . Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. Am J Epidemiol. 2015; 181(6):406-21. PMC: 4402340. DOI: 10.1093/aje/kwu290. View

13.

Hawkes J, Yan B, Chan T, Krueger J . Discovery of the IL-23/IL-17 Signaling Pathway and the Treatment of Psoriasis. J Immunol. 2018; 201(6):1605-1613. PMC: 6129988. DOI: 10.4049/jimmunol.1800013. View

14.

Anderson L, Gadalla S, Morton L, Landgren O, Pfeiffer R, Warren J . Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies. Int J Cancer. 2009; 125(2):398-405. PMC: 2692814. DOI: 10.1002/ijc.24287. View

15.

Szodoray P, Jonsson R . The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren's syndrome. Scand J Immunol. 2005; 62(5):421-8. DOI: 10.1111/j.1365-3083.2005.01688.x. View

16.

Atallah-Yunes S, Murphy D, Noy A . HIV-associated Burkitt lymphoma. Lancet Haematol. 2020; 7(8):e594-e600. DOI: 10.1016/S2352-3026(20)30126-5. View

17.

Schneider P, Mackay F, Steiner V, Hofmann K, Bodmer J, Holler N . BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999; 189(11):1747-56. PMC: 2193079. DOI: 10.1084/jem.189.11.1747. View

18.

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

19.

Hu S, Zhou D, Wu Y, Zhao Y, Wang S, Han B . Autoimmune disease-associated non-Hodgkin's lymphoma-a large retrospective study from China. Ann Hematol. 2018; 98(2):445-455. DOI: 10.1007/s00277-018-3515-2. View

20.

Simard J, Baecklund F, Chang E, Baecklund E, Hjalgrim H, -Olov Adami H . Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes. Int J Cancer. 2012; 132(11):2659-66. DOI: 10.1002/ijc.27944. View