Cancer in first-degree relatives of people with celiac disease

Background: Celiac disease (CD) has been linked to cancer, especially lymphoproliferative malignancy (LPM). Earlier research has shown that first-degree relatives (FDRs) to individuals with CD are at increased risk of autoimmunity including CD, but data on their risk of cancer are scarce and contradictory. We aimed to assess whether Swedish FDRs to individuals with CD are at increased risk of cancer. Methods: Individuals with CD (identified through biopsy reports equal to Marsh grade III) were matched on sex, age, county, and calendar year with up to 5 control individuals. All FDRs (father, mother, sibling, offspring) of CD individuals ("celiac FDRs": n = 109,391) and controls (n = 548,465) were identified through Swedish healthcare registries. Through Cox regression, we calculated hazard ratios (HRs) for cancer incidence (all cancer, breast cancer, gastrointestinal cancer, and LPM). Results: During follow-up, celiac FDRs experienced 10,750 unique cancers as opposed to 54,686 in-control FDRs. Celiac FDRs were at a slightly lower risk of any cancer (HR 0.97, 95% confidence interval [CI] 0.95-0.99), partially due to the lower risk of breast cancer (HR 0.92, 95% CI 0.87-0.98). The relative risks of LPM (HR 0.99, 95% CI 0.91-1.08) and gastrointestinal cancer (HR 0.98, 95% CI 0.93-1.03) were both close to 1. As opposed to earlier research, we found no excess risk of LPM in siblings to individuals with CD (HR 0.98, 95% CI 0.81-1.19). Conclusion: Celiac FDRs are not at increased risk of cancer, including LPM, arguing that shared genetics is unlikely to explain previous reports of an excess risk of LPM in patients with CD.