Systemic chronic inflammation and increased production of pro-inflammatory molecules may favor the onset of metabolic syndrome (MetS), according to Giovanni Cioffi, MD. “This is why patients with chronic inflammatory rheumatic diseases (RMD) have an increased prevalence of MetS when compared with those without these diseases,” he says. “Furthermore, several studies have found that MetS is associated with increased risk of cancer, with a predisposition for specific types of cancer. Therefore, my colleagues and I hypothesized that a very close association between these two conditions exists in patients with chronic inflammatory RMD.”
To test this hypothesis, Dr. Cioffi and colleagues conducted a combination retrospective/prospective study for a paper published in Arthritis, Research & Therapy. “Our aim was to assess prevalence/incidence and factors related to the development of cancer in a large cohort of patients with chronic inflammatory RMD and to evaluate whether MetS and its components are associated with cancer and, if so, which types of cancer, independent of traditional markers of inflammation and disease activity,” Dr. Cioffi adds.
MetS Is Strongest Cancer Risk Factor
The study population, recruited between March 2014 and April 2016, included 474 non-institutionalized patients older than 18 who underwent clinical, laboratory, and echocardiographic evaluations. They were closely followed after recruitment for a mean of 42 months.
Among participants, 9.7% had a diagnosis of cancer made before recruitment or during follow-up. Of these patients, 61% had a malignancy traditionally associated with MetS (carcinoma of the thyroid = 6, breast = 5, pancreas = 4, colon = 4, uterus = 3, kidney = 3, prostate = 2, and ovary = 1). Cancer was diagnosed in 29% of patients with MetS and in 6% of those without MetS. Beyond MetS, cancer was associated with older age and increased inflammatory disease activity.
The researchers observed four key findings:
- In patients with chronic inflammatory RMD, the development of cancer was not uncommon, and nearly two-thirds of malignancies belonged to those traditionally related to MetS.
- More than one-quarter of patients with MetS developed cancer, indicating that MetS represents the strongest risk factor for cancer, independently of the various components by which MetS is recognized.
- A diagnosis of cancer was positively associated with the number of MetS components identified in each patient with RMD.
- MetS provided additional information to the already documented effect of increased inflammatory disease activity on carcinogenesis in patients with RMD.
MetS Assessment Critical in Patients With RMD
“Patients with MetS have a higher magnitude of inflammation and a fivefold risk of developing cancer compared with counterparts who have not,” Dr. Cioffi says. “Furthermore, the risk of developing cancer is 10-fold higher in patients who have two or more MetS components than those who have less than two components. Our findings indicate that in patients with chronic inflammatory RMD, the relationship between higher magnitude of chronic inflammation and the risk of developing cancer is magnified by the presence of MetS and directly proportioned to the metabolic risk components (Table).”
Based on their findings, the researchers suggest that an accurate assessment of MetS be required in patients with RMD as a potential measure of clinical outcomes, including the risk of cancer. “It should be noted that MetS is a reversible status and that several interventions—such as regular physical exercise, healthful diet, and hypoglycemic drugs and/or lipid lowering agents—can effectively fight MetS,” Dr. Cioffi adds.
Dr. Cioffi and colleagues would like to see future research aimed at assessing the potential positive role of specific diets designed to control MetS. “In addition, we would welcome prospective investigations that examine the potentially favorable role of biologic disease-modifying anti-rheumatic drugs in the fight against cancer and/or the positive effects of pharmacological and non-pharmacological interventions to avoid the development of MetS and its detrimental effects.”