Risk of Cancer in Patients With Primary Sjögren's Disease and Their Relatives

Familial clustering and HLA haplotype association studies suggest that genetic factors disrupting the regulation of the immune system may predispose to risk of both neoplasms and autoimmune diseases, potentially leading to an increased frequency of cancer development in patients with primary Sjögren's disease (SjD), as well as their relatives. In this study, we aimed to assess the risk of cancer in patients with primary SjD and their close relatives.

Primary SjD patients who were actively followed-up in the rheumatology outpatient clinic at Gazi University Hospital and who met the 2016 ACR-EULAR classification criteria for primary SjD were included in the study. Data on cancer history in patients and their relatives were collected through direct face-to-face interviews and telephone surveys with the patients. The risk of developing cancer was calculated by comparing it with the general population of Turkey obtained from the Global Cancer Observatory of the World Health Organization International Agency for Research on Cancer (GLOBOCAN).

A total of 323 primary SjD patients (F/M: 313/10, mean age: 56 ± 11) and their 1750 close relatives (parents, siblings, and children) were studied. Among SjD patients, 29 (9%) had a history of malignancy. Of these, 19 (5.9%) were solid organ and 10 (3.1%) were hematological malignancies. Breast cancer was the most common solid tumor. The median follow-up was 3.6 years, and the calculated standardized incidence ratio (SIR) for all cancers was 3.3 (95% CI: 2.2-4.7, p < 0.001). Leukemia or lymphoma cases had an SIR of 22.5 (95% CI: 10.8-41.4, p < 0.001). Among 313 women, seven cases of breast cancer had an SIR of 3.8 (95% CI: 1.5-7.9, p < 0.001). Risk of malignancy in patients with SjD did not differ based on age, gender, smoking history, Schirmer test result, laboratory parameters including anti-SSA, anti-SSB, ANA, complement levels, ESSDAI status, or Focus score, but it was higher in the presence of a cancer among close relatives. A total of 128 (43.3%) patients with SjD had at least one close relative with cancer (176 cancer cases in total), giving an SIR of 3.5 (95% CI: 3.0-4.1, p < 0.001). The average age of close relatives with cancer was 58 ± 10 years; 56% were male, and 7.4% were active smokers.

Our results suggest that not only patients with primary SjD but also their close relatives have an increased risk of developing cancer compared with the general population.