An epidemiological study estimating the burden of cancer risk in patients with Raynaud’s phenomenon

Introduction/objective: Raynaud's phenomenon (RP) is a common vasospastic condition that may develop secondary to cancer and/or in association with systemic autoimmune rheumatic diseases (SARDs). We aimed to estimate the risk of cancer in RP without known SARDs, phenotypically akin to 'primary' RP. Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥ 2 ICD (I73.0) codes, excluding SARDs. Comparators had ≥ 2 irritable bowel syndrome ICD (K58) codes: selected with similar epidemiology to RP, and without any known excess in cancer risk. Cohorts were stratified by age (< 45 and ≥ 45 years). Our primary outcome was any cancer event. Secondary outcomes were rates of specific cancers: head and neck, digestive, thorax, skin, breast, haematological, male/female genital. Risk of each outcome was compared using 1:1 propensity score-matched Cox proportional hazard models. Results: Among 34,582 (< 45 years) and 68,836 (≥ 45 years) matched pairs, the hazard ratio (HR) of any cancer was higher in RP: < 45 [1.11 (1.03, 1.19)] and ≥ 45 [1.08 (1.05, 1.11)]. Cancer-specific risks were calculated. RP was associated in both age groups with increased risk of thorax (HR 2.077 & 1.433), skin (HR 1.202 &1.213), and haematological (HR 1.647 & 1.338) cancers. RP was associated with decreased risk of digestive cancer (HR 0.686 & 0.894). Conclusion: RP was associated with an increased risk of cancer, independent of age. We also describe varying cancer-specific risks. Future research is warranted to confirm and explore these novel observations, including potentially shared pathobiological mechanisms. Key Points • RP was associated with an overall increased risk of all cancers in younger (<45years) and older (≥45 years) individuals. • There was an increased risk of certain (e.g., thorax, skin, and haematological) cancers with RP. • A reduced risk of cancer was also noted for certain cancers, especially GI-related. • Future research should confirm and explore these observations, including the pathobiology underpinning potential cancer risk in RP.