Objectives: The study was conducted to improve our understanding of the epidemiology of cancer in systemic sclerosis (SSc) by evaluating the incidence, prevalence, relative risk of overall and site-specific malignancies, predictors and cancer-attributable mortality. Methods: MEDLINE, CINAHL, EMBASE and Cochrane Library (inception-May 2012) were searched. Estimates were combined using a random effects model. Consistency was evaluated using the I 2 statistic. Results: 4876 citations were searched to identify 60 articles. The average incidence of malignancy in SSc was 14 cases/1000 person-years; the prevalence ranged between 4%-22%. Cancer was the leading cause of non-SSc related deaths with a mean of 38%. Overall SIR for all-site malignancy risk was 1.85 (95%CI 1.52, 2.25; I 2 76%). There was a greater risk of lung (SIR 4.69, 95%CI 2.84, 7.75; I 2 93%) and haematological (SIR 2.58, CI 95% 1.75, 3.81; I 2 0%) malignancies, including non-Hodgkin's lymphoma (SIR 2.55, 95%CI 1.40, 4.67; I 2 0%). SSc patients were at a higher risk of leukemia (SIR 2.79, 95%CI 1.22, 6.37; I 2 0%), malignant melanoma (SIR 2.92, 95%CI 1.76, 4.83; I 2 35%), liver (SIR 4.75, 95%CI 3.09, 7.31; I 2 0%), cervical (SIR 2.28, 95%CI 1.26, 4.09; I 2 54%) and oropharyngeal (SIR 5.0, 95%CI 2.18, 11.47; I 2 58%) cancers. Risk factors include a-RNAP I/III seropositivity, male sex, and late onset SSc. Smoking and longstanding interstitial lung disease increase the risk of lung cancer; Barrett's esophagus and a positive family history of breast cancer, respectively, increase the risk of esophageal adenocarcinoma and breast cancer. Conclusions: SSc patients have a twofold increase in all-site malignancy, and greater risk of lung and haematological malignancies that contribute significantly to mortality. Vigilance should be considered in SSc patients with risk factors for cancer.
