Familial Risks and Proportions Describing Population Landscape of Familial Cancer

Simple Summary Familial cancer can be defined through the occurrence of the same cancer in two or more family members. Hereditary cancer is a narrower definition of high-risk familial aggregation through identified predisposing genes. The absence of correlation between spouses for risk of most cancers, particularly those not related to tobacco smoking or solar exposure, suggests that familial cancers are mainly due to genetic causes. The aim of the present study was to define the frequency and increased risk for familial cancer. Data on 31 of the most common cancers were obtained from the Swedish Family-Cancer Database and familial relative risks (SIRs) were estimated between persons with or without family history of the same cancer in first-degree relatives. Practically all cancers showed a familial risk, with an SIR most commonly around two, or a doubling of the risk because of family history. Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20-84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.

Automated summary

This study analyzed data from the Swedish Family-Cancer Database to determine the frequency and increased risk for familial cancer, finding that almost all cancers showed a familial risk, with most risks being around two-fold due to family history. High-risk family history should be carefully considered for management, including targeted genetic testing, while medical and behavioral interventions are recommended for familial clustering with no feasible genetic testing.