Risk of Cancer in Patients with Rheumatoid Arthritis Compared with the General Population: A Nationwide Cohort Study in Lithuania
Abstract
1. Background
2. Methods
2.1. Dataset
2.2. Study Design and Population
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Forabosco, P.; Bouzigon, E.; Ng, M.Y.; Hermanowski, J.; Fisher, S.A.; Criswell, L.A.; Lewis, C.M. Meta-analysis of genome-wide linkage studies across autoimmune diseases. Eur. J. Hum. Genet. 2009, 17, 236–243. [Google Scholar] [CrossRef][Green Version]
- Zhernakova, A.; van Diemen, C.C.; Wijmenga, C. Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat. Rev. Genet. 2009, 10, 43–55. [Google Scholar] [CrossRef]
- Hemminki, K.; Liu, X.; Ji, J.; Sundquist, J.; Sundquist, K. Effect of autoimmune diseases on risk and survival in histology-specific lung cancer. Eur. Respir. J. 2012, 40, 1489–1495. [Google Scholar] [CrossRef] [PubMed]
- Simon, T.A.; Thompson, A.; Gandhi, K.K.; Hochberg, M.C.; Suissa, S. Incidence of malignancy in adult patients with rheumatoid arthritis: A meta-analysis. Arthritis Res. Ther. 2015, 17, 212. [Google Scholar] [CrossRef] [PubMed]
- Beydon, M.; Pinto, S.; De Rycke, Y.; Fautrel, B.; Mariette, X.; Seror, R.; Tubach, F. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg. Health Eur. 2023, 35, 100768. [Google Scholar] [CrossRef] [PubMed]
- Bhandari, B.; Basyal, B.; Sarao, M.S.; Nookala, V.; Thein, Y. Prevalence of cancer in rheumatoid arthritis: Epidemiological study based on the national health and nutrition examination survey (NHANES). Cureus 2020, 12, e7870. [Google Scholar] [CrossRef] [PubMed]
- Smitten, A.L.; Simon, T.A.; Hochberg, M.C.; Suissa, S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res. Ther. 2008, 10, R45. [Google Scholar] [CrossRef] [PubMed]
- Chakravarty, E.F.; Genovese, M.C. Associations between rheumatoid arthritis and malignancy. Rheum. Dis. Clin. N. Am. 2004, 30, 271–284, vi. [Google Scholar] [CrossRef] [PubMed]
- Kedra, J.; Seror, R.; Dieudé, P.; Constantin, A.; Toussirot, E.; Kfoury, E.; Masson, C.; Cornec, D.; Dubost, J.J.; Marguerie, L.; et al. Lymphoma complicating rheumatoid arthritis: Results from a French case-control study. RMD Open 2021, 7, e001698. [Google Scholar] [CrossRef] [PubMed]
- Hellgren, K.; Di Giuseppe, D.; Smedby, K.E.; Sundström, C.; Askling, J.; Baecklund, E.; ARTIS study group. Lymphoma risks in patients with rheumatoid arthritis treated with biological drugs-a Swedish cohort study of risks by time, drug and lymphoma subtype. Rheumatology 2021, 60, 809–819. [Google Scholar] [CrossRef] [PubMed]
- Smedby, K.E.; Hjalgrim, H.; Askling, J.; Chang, E.T.; Gregersen, H.; Porwit-MacDonald, A.; Sundström, C.; Åkerman, M.; Melbye, M.; Glimelius, B.; et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J. Natl. Cancer Inst. 2006, 98, 51–60. [Google Scholar] [CrossRef] [PubMed]
- Schoninger, S.; Homsi, Y.; Kreps, A.; Milojkvovic, N. A case of multiple myeloma misdiagnosed as seronegative rheumatoid arthritis and review of relevant literature. Case Rep. Rheumatol. 2018, 2018, 9746241. [Google Scholar] [CrossRef] [PubMed]
- Edavalath, S.; Chowdhury, A.C.; Phatak, S.; Misra, D.P.; Verma, R.; Lawrence, A. Multiple myeloma masquerading as severe seropositive rheumatoid arthritis with subcutaneous nodules and mononeuritis multiplex. Int. J. Rheum. Dis. 2017, 20, 1297–1302. [Google Scholar] [CrossRef] [PubMed]
- Luo, X.; He, Y.; Xu, W.; Liu, M.; Zhao, Z.; Peng, L.; He, C.; Chen, J. The risk of leukemia in patients with rheumatoid arthritis: A systematic review and meta-analysis. Clin. Rheumatol. 2021, 40, 1283–1289. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Zhou, L.; Xia, D.; Wang, J. Rheumatoid arthritis reduces the risk of colorectal cancer through immune inflammation mediation. J. Cell Mol. Med. 2024, 28, e18515. [Google Scholar] [CrossRef] [PubMed]
- Raaschou, P.; Simard, J.F.; Hagelberg, C.A.; Askling, J. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: Cohort study based on nationwide prospectively recorded data from Sweden. BMJ 2016, 352, i262. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.-L.; Yin, W.-J.; Zhou, L.-Y.; Zhou, G.; Liu, K.; Hu, C.; Zuo, X.-C.; Wang, Y.-F. Risk of non-melanoma skin cancer for rheumatoid arthritis patients receiving TNF antagonist: A systematic review and meta-analysis. Clin. Rheumatol. 2020, 39, 769–778. [Google Scholar] [CrossRef] [PubMed]
- Wheeler, A.M.; Roul, P.; Yang, Y.; Brittan, K.M.; Sayles, H.; Singh, N.; Sauer, B.C.; Cannon, G.W.; Baker, J.F.; Mikuls, T.R.; et al. Risk of prostate cancer in US veterans with rheumatoid arthritis. Arthritis Care Res. 2023, 75, 785–792. [Google Scholar] [CrossRef] [PubMed]
- Yang, T.O.; Floud, S.; Reeves, G.K. Rheumatoid arthritis and cancer risk in the million women study. Int. J. Epidemiol. 2024, 53, dyae006. [Google Scholar] [CrossRef] [PubMed]
| Patient Characteristics | Male | % | Female | % | Total | % |
|---|---|---|---|---|---|---|
| Number of patients | 2340 | 19.94 | 9398 | 80.06 | 11,738 | 100.00 |
| Person-years | 11,772.01 | 53,115.25 | 64,887.26 | |||
| Mean age at diagnosis, years (±SD) | 58.38 (14.29) | 58.77 (14.21) | 58.69 (14.22) | |||
| Age at RA diagnosis, years | ||||||
| <40 | 247 | 10.56 | 924 | 9.83 | 1171 | 9.98 |
| 40–50 | 360 | 15.38 | 1372 | 14.60 | 1732 | 14.76 |
| 50–59 | 634 | 27.09 | 2755 | 29.31 | 3389 | 28.87 |
| 60–69 | 576 | 24.62 | 2107 | 22.42 | 2683 | 22.86 |
| ≥70 | 523 | 22.35 | 2240 | 23.83 | 2763 | 23.54 |
| Types of cancer per subject | ||||||
| 0 | 2118 | 90.51 | 8907 | 94.78 | 11,025 | 93.93 |
| 1 | 210 | 8.97 | 472 | 5.02 | 682 | 5.81 |
| ≥2 | 12 | 0.51 | 19 | 0.20 | 31 | 0.26 |
| Exposure to biological therapy | ||||||
| Yes | 189 | 8.08 | 726 | 7.73 | 915 | 7.80 |
| No | 2151 | 91.92 | 8672 | 92.27 | 10,823 | 92.20 |
| Diagnosis | ICD-10 | Male | Female | Overall | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Obs | Exp | SIR | 95% CI | Obs | Exp | SIR | 95% CI | Obs | Exp | SIR | 95% CI | |||||
| All Sites | C00–C96 | 234 | 185.03 | 1.26 | 1.11 | 1.44 | 512 | 450.42 | 1.14 | 1.04 | 1.24 | 746 | 635.45 | 1.17 | 1.09 | 1.26 |
| Lip | C00 | 0 | 0.31 | - | - | - | 0 | 0.34 | - | - | - | 0 | 0.66 | - | - | - |
| Mouth and pharynx | C01–C14 | 2 | 6.01 | 0.33 | 0.08 | 1.33 | 1 | 4.69 | 0.21 | 0.03 | 1.51 | 3 | 10.70 | 0.28 | 0.09 | 0.87 |
| Esophagus | C15 | 2 | 3.79 | 0.53 | 0.13 | 2.11 | 1 | 1.88 | 0.53 | 0.07 | 3.77 | 3 | 5.67 | 0.53 | 0.17 | 1.64 |
| Stomach | C16 | 8 | 9.67 | 0.83 | 0.41 | 1.65 | 16 | 17.72 | 0.90 | 0.55 | 1.47 | 24 | 27.39 | 0.88 | 0.59 | 1.31 |
| Other digestive organs | C17, C26, C48 | 0 | 0.59 | - | - | - | 2 | 2.29 | 0.87 | 0.22 | 3.50 | 2 | 2.88 | 0.70 | 0.17 | 2.78 |
| Colon | C18 | 7 | 9.00 | 0.78 | 0.37 | 1.63 | 14 | 24.69 | 0.57 | 0.34 | 0.96 | 21 | 33.69 | 0.62 | 0.41 | 0.96 |
| Rectum, rectosigmoid, anus | C19–C21 | 4 | 7.46 | 0.54 | 0.20 | 1.43 | 9 | 16.39 | 0.55 | 0.29 | 1.06 | 13 | 23.85 | 0.55 | 0.32 | 0.94 |
| Liver | C22 | 10 | 3.08 | 3.24 | 1.74 | 6.03 | 4 | 4.66 | 0.86 | 0.32 | 2.29 | 14 | 7.74 | 1.81 | 1.07 | 3.05 |
| Gallbladder, bile ducts | C23, C24 | 1 | 0.93 | 1.07 | 0.15 | 7.61 | 0 | 4.07 | - | - | - | 1.00 | 5.00 | 0.20 | 0.03 | 1.42 |
| Pancreas | C25 | 5 | 5.37 | 0.93 | 0.39 | 2.24 | 18 | 15.77 | 1.14 | 0.72 | 1.81 | 23 | 21.14 | 1.09 | 0.72 | 1.64 |
| Nasal cavity, middle ear, accessory sinuses | C30, C31 | 0 | 0.31 | - | - | - | 0 | 0.70 | - | - | - | 0 | 1.01 | - | - | - |
| Larynx | C32 | 0 | 3.58 | - | - | - | 0 | 0.73 | - | - | - | 0 | 4.31 | - | - | - |
| Lung, trachea | C33, C34 | 27 | 25.15 | 1.07 | 0.74 | 1.57 | 20 | 18.20 | 1.10 | 0.71 | 1.70 | 47 | 43.35 | 1.08 | 0.81 | 1.44 |
| Bone and connective tissue | C40, C41, C45–C47, C49 | 1 | 0.92 | 1.09 | 0.15 | 7.72 | 6 | 3.05 | 1.97 | 0.89 | 4.39 | 7 | 3.97 | 1.77 | 0.84 | 3.70 |
| Skin, melanoma | C43 | 3 | 2.46 | 1.22 | 0.39 | 3.78 | 12 | 10.53 | 1.14 | 0.65 | 2.01 | 15 | 12.99 | 1.15 | 0.70 | 1.92 |
| Skin, nonmelanoma | C44 | 26 | 17.46 | 1.49 | 1.01 | 2.19 | 113 | 74.27 | 1.52 | 1.27 | 1.83 | 139 | 91.73 | 1.52 | 1.28 | 1.79 |
| Breast | C50 | 0 | 0.27 | - | - | - | 87 | 88.27 | 0.99 | 0.80 | 1.22 | 87 | 88.54 | 0.98 | 0.80 | 1.21 |
| Vulva | C51 | - | - | - | - | - | 1 | 3.06 | 0.33 | 0.05 | 2.32 | - | - | - | - | - |
| Other female and male genital organs | C52, C57–C58, C60, C63 | 0 | 0.56 | - | - | - | 3 | 2.05 | 1.46 | 0.47 | 4.53 | - | - | - | - | - |
| Cervix uteri | C53 | - | - | - | - | - | 16 | 18.29 | 0.87 | 0.54 | 1.43 | - | - | - | - | - |
| Corpus uteri | C54, C55 | - | - | - | - | - | 43 | 38.61 | 1.11 | 0.83 | 1.50 | - | - | - | - | - |
| Ovary | C56 | - | - | - | - | - | 19 | 21.09 | 0.90 | 0.57 | 1.41 | - | - | - | - | - |
| Prostate | C61 | 78 | 55.74 | 1.40 | 1.12 | 1.75 | - | - | - | - | - | - | - | - | - | - |
| Testis | C62 | 0 | 0.19 | - | - | - | - | - | - | - | - | - | - | - | - | - |
| Kidney | C64 | 15 | 8.12 | 1.85 | 1.11 | 3.06 | 17 | 15.90 | 1.07 | 0.66 | 1.72 | 32 | 24.03 | 1.33 | 0.94 | 1.88 |
| Other urinary tract | C65, C66, C68 | 2 | 0.54 | 3.69 | 0.92 | 14.77 | 0 | 1.19 | - | - | - | 2 | 1.73 | 1.16 | 0.29 | 4.63 |
| Urinary bladder | C67 | 4 | 6.54 | 0.61 | 0.23 | 1.63 | 6 | 4.62 | 1.30 | 0.58 | 2.89 | 10 | 11.16 | 0.90 | 0.48 | 1.67 |
| Eye and adnexa | C69 | 0 | 0.28 | - | - | - | 2 | 0.92 | 2.18 | 0.55 | 8.72 | 2 | 1.19 | 1.68 | 0.42 | 6.70 |
| Central nervous system | C70–C72 | 2 | 2.36 | 0.85 | 0.21 | 3.39 | 9 | 7.38 | 1.22 | 0.63 | 2.34 | 11 | 9.73 | 1.13 | 0.63 | 2.04 |
| Thyroid | C73 | 2 | 0.82 | 2.43 | 0.61 | 9.73 | 12 | 12.91 | 0.93 | 0.53 | 1.64 | 14 | 13.74 | 1.02 | 0.60 | 1.72 |
| Other endocrine organs | C74, C75 | 0 | 0.15 | - | - | - | 1 | 0.39 | 2.59 | 0.37 | 18.42 | 1 | 0.53 | 1.87 | 0.26 | 13.28 |
| Other and ill-defined sites | C76–C80 | 7 | 4.60 | 1.52 | 0.72 | 3.19 | 6 | 9.31 | 0.64 | 0.29 | 1.43 | 13 | 13.92 | 0.93 | 0.54 | 1.61 |
| Non-Hodgkin lymphoma | C81 | 1 | 0.20 | 4.90 | 0.69 | 34.77 | 3 | 0.75 | 4.00 | 1.29 | 12.41 | 4 | 0.95 | 4.19 | 1.57 | 11.18 |
| Hodgkin lymphoma | C82–C85 | 14 | 2.84 | 4.93 | 2.92 | 8.32 | 29 | 9.57 | 3.03 | 2.11 | 4.36 | 43 | 12.41 | 3.46 | 2.57 | 4.67 |
| Other and unspecified malignant neoplasms of lymphoid, hematopoietic and related tissue | C88, C96 | 2 | 0.12 | 17.01 | 4.25 | 68.01 | 0 | 0.34 | - | - | - | 2.00 | 0.46 | 4.39 | 1.10 | 17.54 |
| Myeloma | C90 | 1 | 1.57 | 0.64 | 0.09 | 4.53 | 16 | 5.33 | 3.00 | 1.84 | 4.90 | 17 | 6.89 | 2.47 | 1.53 | 3.97 |
| Leukemia | C91–C95 | 9 | 4.03 | 2.23 | 1.16 | 4.29 | 25 | 10.45 | 2.39 | 1.62 | 3.54 | 34 | 14.48 | 2.35 | 1.68 | 3.29 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Share and Cite
Gedvilaitė, V.; Kačėnienė, A.; Jonušienė, G.; Dadonienė, J.; Miltinienė, D.; Deresevičienė, G.; Smailytė, G. Risk of Cancer in Patients with Rheumatoid Arthritis Compared with the General Population: A Nationwide Cohort Study in Lithuania. Medicina 2026, 62, 290. https://doi.org/10.3390/medicina62020290
Gedvilaitė V, Kačėnienė A, Jonušienė G, Dadonienė J, Miltinienė D, Deresevičienė G, Smailytė G. Risk of Cancer in Patients with Rheumatoid Arthritis Compared with the General Population: A Nationwide Cohort Study in Lithuania. Medicina. 2026; 62(2):290. https://doi.org/10.3390/medicina62020290
Chicago/Turabian StyleGedvilaitė, Vaida, Augustė Kačėnienė, Gintarė Jonušienė, Jolanta Dadonienė, Dalia Miltinienė, Giedrė Deresevičienė, and Giedrė Smailytė. 2026. "Risk of Cancer in Patients with Rheumatoid Arthritis Compared with the General Population: A Nationwide Cohort Study in Lithuania" Medicina 62, no. 2: 290. https://doi.org/10.3390/medicina62020290
APA StyleGedvilaitė, V., Kačėnienė, A., Jonušienė, G., Dadonienė, J., Miltinienė, D., Deresevičienė, G., & Smailytė, G. (2026). Risk of Cancer in Patients with Rheumatoid Arthritis Compared with the General Population: A Nationwide Cohort Study in Lithuania. Medicina, 62(2), 290. https://doi.org/10.3390/medicina62020290

