Colorectal cancer risk in association with colorectal cancer as a second malignancy in relatives: a nationwide cohort study

Background: Increasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk. Methods: In this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group. Results: A cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65–1.79) and 1.50 (1.32–1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system. Conclusions: Individuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships.