Impact of Family History on Colorectal Cancer Risk in Inflammatory Bowel Disease and in Matched General Population Comparators.
BACKGROUND /Aims: Few studies have explored how family history of colorectal cancer (CRC) affects CRC incidence in inflammatory bowel disease (IBD). We estimated CRC incidence rates (IRs) and IR differences, by family history of CRC, and the interaction between IBD and family history. METHODS Nationwide, register-based cohort study 1996-2023, including patients with IBD and matched (age, sex, parish, year) comparators from the general population. The exposure was family history, defined as the number of first-degree relatives (parent, sibling, or child) and their age at CRC diagnosis (<50 or ≥50 years). RESULTS During a median follow-up of 11 years, 1,882 CRC events occurred in 124,387 patients with IBD (IR 1.17[95%CI:1.12-1.23]/1,000 person-years) and 14,177 CRC events in 1,213,641 comparators (IR 0.88[95%CI:0.86-0.89]/1,000 person-years). In IBD, the greatest CRC risk increase was seen in those with ≥2 affected relatives: 2.69(95%CI:0.60-4.78) additional cases per 1,000 person-years versus no family history, while risk increase with early-onset CRC heredity was modest: 0.42(95%CI: -0.47-1.31)/1,000 person-years. The IRs were comparable between patients and matched comparators with the same family history, except among those without family history of CRC, where the CRC incidence was higher in IBD. The relative effect of family history was weaker in IBD, where the baseline CRC risk was already elevated. CONCLUSION On the absolute scale, family history of CRC increased CRC incidence similarly in IBD and matched comparators, with the greatest increase in individuals with multiple affected relatives. Guidelines advise special attention to patients with family history of early-onset CRC; our findings raise the question if surveillance strategies should instead prioritize patients with multiple affected relatives.