Familial risks for colorectal cancer show evidence on recessive inheritance

Recent molecular genetic data have become available on a recessive inheritance in colorectal cancer (CRC). We wanted to search for evidence for recessive inheritance from a population-based family data set, which is not sensitive to reporting or ascertainment bias. The nationwide Swedish Family-Cancer Database covered 10.3 million individuals whose invasive CRCs of adenocarcinoma histology were followed from 1991 to 2000. Age of the offspring and parental populations was limited to less than 69 years. Standardized incidence ratios (SIRs) were calculated for site-specific CRC in offspring whose parents or siblings were diagnosed with CRC. A total of 6,774 offspring were recorded with CRC, whose risk was 2.13 when a parent was diagnosed with CRC and it was 2.75 when a sibling was affected. The SIRs for right-sided colon cancer were 7.53 among siblings and 3.66 among offspring of affected parents, giving a 1.8-fold excess familial risk among siblings. Colon cancer among the 0- to 68-year-old population accounted for about 25% of all colon cancers. Examination of all cancers in family members of the affected siblings did not reveal large contribution by known syndromes, such as hereditary nonpolyposis colorectal cancer. The most likely explanation to the high risk of right-sided colon cancer among siblings is a recessive inheritance, which would account for 0.75% of all CRCs. Its high prevalence and predilection to right-sided colon suggest that only a small proportion of this familial aggregation could be due to MYH mutations.