Study Examines Links Around Chronic Inflammatory Rheumatic Disease, Cancer

In patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMD), the presence of metabolic syndrome (MetS) indicates an increased risk of cancer.

The association between metabolic syndrome (MetS) and a higher risk of cancer has already been established. Now, however, a new study of patients indicates an increased risk of cancer in those with chronic inflammatory rheumatic and musculoskeletal diseases (RMD) as well.

More than a quarter of patients with RMD in the study developed MetS over time, researchers from Italy said in a study published in Arthritis Research and Therapy, and a diagnosis of cancer was positively associated with the number of MetS component diseases identified in each patient.

MetS represents a cluster of cardiometabolic disorders including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia, and hypertension. Systemic chronic inflammation and increased production of pro-inflammatory cytokines may favor the onset of MetS, explaining why RMD patients with diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) have a higher prevalence of MetS. Patients with RA, PsA, and AS also have a higher risk of cancer.

The study included 474 adult subjects with RMD involved in a cardiovascular prevention program—predominantly females with a long duration of chronic inflammatory rheumatic disease. Of the subjects, 244 had RA, 134 PsA, and 96 AS. The study was both retrospective and prospective, with cancer diagnosed before recruitment as well as during follow-up. All were patients who visited a rheumatology center in Verona from 2014 to 2016 and were followed through November 2019.

Researchers found that 76 of the 474 patients had MetS, with 22 of them (29%) diagnosed with cancer. In contrast, of the 398 patients without MetS, only 24 (6%; P < 0.001) developed cancer. Of the combined total of 46 subjects who developed cancer, 28 (61%) developed malignancies traditionally associated with MetS, including cancers of the thyroid, breast, pancreas, and colon.

MetS was the strongest cancer risk factor independent of its various component conditions, the authors said. Furthermore, the number of MetS conditions was associated with risk of developing cancer. Thirty-eight of the 46 cancer cases (83%) developed in those who had 2 to 5 MetS components. It was rare for cancer to develop in those with 0 to 1 Mets components (8 cases, or 17%).

The researchers were able to build a performance indicator considering the 3 variables (RA, PsA, and AS) that was highly sensitive for cancer development. The indicator ranged from a score of 0 to 8, assigning 5 points to patients with MetS, 2 to those with moderate to high disease activity, and 1 to those over age 60. They considered the indicator highly useful in identifying a subgroup of RA/PsA/AS patients with a very low risk (<1%) for cancer.

“In light of our results, an increasingly accurate assessment of MetS would be required in patients with RA/AS/PsA as potential measure of clinical outcomes … including the risk of cancer,” the authors wrote.

Future needs include investigations of the potential effectiveness of biologic disease-modifying anti-rheumatic drugs in the fight against cancer as well as the effects of pharmacological and nonpharmacological interventions that elude the development of MetS and its detrimental effects, the authors wrote.


Cioffi G, Viapiana O, Tarantini L, et al. The troubling liaison between cancer and metabolic syndrome in chronic inflammatory rheumatic diseases. Arthritis Res Ther. 2021;23(1):89. doi:10.1186/s13075-021-02465-3