Abstract 2556: Family history of colorectal cancer in half-siblings as important as in siblings

Abstract

Abstract Background: None of population-based epidemiological studies to date have investigated the familial risk of colorectal cancer (CRC) in half-siblings. We aimed to compare lifetime (0-79 years) cumulative risk (LCR) and relative risk of CRC between siblings and half-siblings of patients with CRC. Methods: A nationwide cohort of first-degree relatives and half-siblings of CRC patients diagnosed in 1958-2012 were extracted from the Swedish Family-Cancer Database, the world's largest of its kind, with >15.7 million individual records. LCR as a tangible measure of absolute risk was also calculated. Standardized incidence ratios (SIRs) were adjusted for age, sex, period at diagnosis, and socioeconomic status. All family histories reported below are exclusive, meaning that risk reported for one affected half-sibling does not include those with both an affected half-sibling and any other first/second-degree relatives. Results: The overall LCR of CRC in siblings of a patient with CRC was 7.2% (8.3% in men; 6.0% in women), which represents 1.8-fold (95%CI = 1.7-1.1.9, n = 1333) increase over the risk in those without any family history of CRC (men 4.5%; women 3.4%). Similarly, significantly increased LCR (5.9%) was found among half-siblings of CRC patients (SIR = 1.7, 95%CI = 1.3-2.0, n = 88; maternal half-sibling: 1.6, 95%CI = 1.1-2.1; paternal half-sibling: 1.7, 95%CI = 1.3-2.3). If a parent and a half-sibling both had CRC, the risk in other half-siblings (SIR = 4.4, 95%CI = 2.8-6.5, n = 24) was closer to that of those with both an affected parent and an affected sibling (SIR = 3.2, 95%CI = 2.9-3.6, n = 281) rather than an affected parent alone (SIR = 1.6, 95%CI = 1.5-1.7, n = 4250). Highly increased risk of CRC was also found in those with two (SIR = 2.4, 95%CI = 1.8-3.1, n = 59) or three (SIR = 9.8, 95%CI = 5.1-17, n = 12) affected siblings, in twin brothers (SIR = 4.0, 95%CI = 2.2-6.6, n = 14), and presumably in men with two affected half-siblings (SIR = 5.3, 95%CI = 1.1-16, n = 3). Other second-degree relatives such as grandparents (SIR = 1.2, 95%CI = 1.1-1.3, n = 318), aunts/uncles (SIR = 1.3, 95%CI = 1.0-1.5, n = 107) without an affected first-degree relative showed minor contributions to the familial risk of CRC, but we found higher risks for those with both an affected first-degree relative and a grandparent (SIR = 3.2, 95%CI = 2.3-4.2, n = 46) or an aunt/uncle (SIR = 2.3, 95%CI = 1.2-4.0, n = 13). Conclusions: This study provides novel information, which is useful for the genetic counseling. In the cancer risk estimation for relatives of CRC patients, a family history of CRC in a half-sibling (even in the absence of an affected first-degree relative) is as important as a family history of CRC in a sibling. Citation Format: Mahdi Fallah, Elham Kharazmi, Kristina Sundquist, Hermann Brenner, Kari Hemminki. Family history of colorectal cancer in half-siblings as important as in siblings. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2556.