Cancer Control Research5R03CA149970-02
Bernatsky, Sasha Ruth
CANCER RISK IN PEDIATRIC-ONSET RHEUMATIC DISEASE
DESCRIPTION (provided by applicant): The association of cancer with autoimmune disease has been under study for years. In adults, there is evidence of increased cancer risk in several autoimmune rheumatic diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). There are essentially no data on malignancy occurrence in pediatric-onset rheumatic diseases such as juvenile SLE and juvenile idiopathic arthritis (JIA, which includes the pediatric equivalent of RA). Extrapolations from adult-onset populations are inappropriate, given clinical differences between these diseases across age groups. Power issues necessitate the use of multi-centre efforts in order to definitely establish the risk in juvenile-onset populations, relative to age and sex matched general population cancer rates. The study objectives are to examine cancer incidence in two multi-centre pediatric rheumatic disease cohorts; one with pediatric-onset SLE and one with JIA, and to determine if this is increased compared to age, sex, and calendar-year general population cancer incidence rates. All patients will be linked to regional tumor registries to determine cancer occurrence over the observation interval. The person-years of follow-up for each subject will be calculated from the date first seen at the respective clinic, and the first of three possible events: death, cancer, or the end of the study interval. Standardized incidence ratios (SIRs) will be calculated as the ratio of observed to expected cancers. Cancers expected will be determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. This study is important, given that survival in pediatric-onset rheumatic disease has improved in the recent past, and there is increasing interest in the morbidity that these patients suffer, long-term. Given the data that has been demonstrated in SLE and RA of adult onset, malignancy risk is of particular concern to children who are affected by these conditions. The information generated from this study will be of crucial importance not only to clinicians, but also to patients and their families. This work will also set the stage for further evaluations. If an increased risk is demonstrated, the researchers will complete further studies to assess the relative importance of disease activity and medication exposures as risk factors for malignancy development in pediatric-onset SLE and JIA. The collaboration and combined resources represented in this application signifies an unprecedented opportunity.