Familial aggregation of early‐onset cancers

This registry‐linkage study evaluates familial aggregation of cancer among relatives of a population‐based series of early‐onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early‐onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early‐onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender‐, age‐ and period‐specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early‐onset cancers were sporadic (98% or more). Among first‐degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72–18), and lowest in melanoma (1.93, 1.05–3.23). Highest relative‐specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43–165) for colorectal cancer and 29 (11–64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early‐onset cancers are mainly sporadic. Findings support high familial aggregation in early‐onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP‐ and HNPCC‐syndromes. The pattern of familial aggregation of early‐onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.