The five major autoimmune diseases increase the risk of cancer: epidemiological data from a large-scale cohort study in China

Abstract

Background: Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases (AIDs). This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese cohort.

Methods: A total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed-up for 38,726.55 patient-years, including those with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic scleroderma (SSc), and idiopathic inflammatory myositis (IIM). Demographic data, cancer incidence, predilecting sites and cancer onset time were recorded and compared among the five AIDs.

Results: Four hundred and thirty (5.3%) patients developed cancer. Their median age was 57.5 years and AID duration was 79.8 months. The estimated total standardized incidence ratio (SIR) of cancer in AIDs patients was 3.37, with the highest SIR observed in IIM (4.31), followed by RA (3.99), SSc (3.77), SS (2.88) and SLE (2.58). The increased SIR of cancers in AID patients showed a female predominance (female vs. male: 3.59 vs. 2.77) and younger patient involvement (age <50 vs. ≥50 years: 4.88 vs. 3.04). Patients with SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder, corpus uteri and cervix uteri. Patients with SS had a significantly high SIR for developing non-Hodgkin's lymphoma. Within 3 years of IIM diagnosis, 74.6% of the patients developed cancer and they had a high risk of ovarian cancer. RA was associated with a wide distribution of scancers, including non-Hodgkin's lymphoma, gynecologic, urinary tract, thyroid gland and lung cancers. SSc patients had increased SIRs for developing cervical uterine, lung, and breast cancers.

Conclusion: Patients with five major AIDs in China had an increased risk of developing cancer, with a predominance in women and younger patients, although cancer incidence, predilection sites and cancer onset time may vary greatly in each AID entity.

Keywords: Sjögren's syndrome; autoimmune disease; cancer risk; epidemiology; idiopathic inflammatory myositis; lupus erythematosus; rheumatoid arthritis; standardized incidence ratio; systemic scleroderma.

FIGURE 1

Flow chart of patient enrollment. Abbreviations: AID, autoimmune disease; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; SS, Sjögren's syndrome; IIM, idiopathic inflammatory myopathies; SSc, systemic sclerosis; CA, cancer

FIGURE 2

Gender‐ and age‐specific standardized incidence ratios (SIRs) in AID patients and subgroups. (A) SIRs for cancer in each sites of female (red) and male (blue) patients. (B) SIRs for cancer in each type of AID in female (red) and male (blue) patients. (C) SIRs for cancer in different age groups (every 10 years) of female (red) and male (blue) patients. (D) SIRs for cancer in each type of AID patients living in urban (red) or rural areas (blue). *: SIRs significantly increased with 95% CI >1; ^† “Others” consists of cancers from eye, mouth, lip, parathyroid, thoracic neoplasms, bone, immunoproliferative diseases and connective tissue. Abbreviations: SIR, standardized incidence ratio; AID, autoimmune disease; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; SS, Sjögren's syndrome; IIM, idiopathic inflammatory myopathies; SSc, systemic sclerosis

FIGURE 3

Site‐specific standardized incidence ratios (SIRs) in AID patients and subgroups. (A) Cancer sites with significantly increased SIRs in all and five types of AIDs. (B) Heatmaps of SIRs for each cancer site in female patients, clustered by AIDs. (C) Heatmaps of SIRs for each cancer site in male patients, clustered by AIDs. Abbreviations: SIR, standardized incidence ratio; AID, autoimmune disease; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; SS, Sjögren's syndrome; IIM, idiopathic inflammatory myopathies; SSc, systemic sclerosis

FIGURE 4

Time interval between the AID diagnosis and cancer diagnosis. Percentages of time interval between diagnosis of AID and cancer of AID‐CA patients, with trend visualized by the smoothing line (blue line). Abbreviations: AID, autoimmune disease; IIM, idiopathic inflammatory myopathies; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS, Sjögren's syndrome; SSc, systemic sclerosis, CA, cancer