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.

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki 00290 Helsinki Finland

Center for Community Based Healthcare Research and Education Department of Functional Pathology School of Medicine Shimane University Izumo 693 8501 Shimane Japan

Center for Primary Health Care Research Lund University 20502 Malmö Sweden

Comprehensive Cancer Center Helsinki University Hospital 00290 Helsinki Finland

Department of Family Medicine and Community Health Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Division of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 580 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center 69120 Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Hopp Children's Cancer Center 69120 Heidelberg Germany

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Survival in Colon, Rectal and Small Intestinal Cancers in the Nordic Countries through a Half Century

Overview on population screening for carriers with germline BRCA mutation in China

Cervical, vaginal and vulvar cancer incidence and survival trends in Denmark, Finland, Norway and Sweden with implications to treatment

Familial Risks for Liver, Gallbladder and Bile Duct Cancers and for Their Risk Factors in Sweden, a Low-Incidence Country