Increased Risk of Colorectal Cancer Among Family Members of All Ages, Regardless of Age of Index Case at Diagnosis

Background & Aims: It is not clear whether familial risk of colorectal cancer (CRC) varies with age of index CRC patients or their relatives. We quantified the risk of CRC in first-degree relatives (FDRs), second-degree relatives, and first-cousin relatives of individuals with CRC, stratified by ages and sexes of index patients and ages of relatives. Methods: CRCs diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and sex-matched CRC-free individuals were selected to form the comparison group. CRC risk in relatives was determined by Cox regression analysis. Results: Of 18,208 index patients diagnosed with CRC, the highest familial risk was observed in FDRs of index CRC patients who were diagnosed at an age younger than 40 years (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.7-3.79). However, familial risk was increased in FDRs even when the index case was diagnosed with cancer at an advanced age (>80 years; HR, 1.76; 95% CI, 1.59-1.94). Ages of relatives and ages of index cases of CRC each affected familial cancer risk; the highest risk was found in young relatives (<50 years) of individuals with early-onset CRC (<40 years; HR, 7.0; 95% CI, 2.86-17.09). Conclusions: All relatives of individuals with CRC are at increased risk for this cancer, regardless of the age of diagnosis of the index patient. Although risk is greatest among young relatives of early-onset CRC cases, relatives of patients diagnosed at advanced ages also have an increased risk.