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Clinical Genetics and Genetic Counseling

Familial Risks for Cancer as the Basis for Evidence-Based Clinical Referral and Counseling

^aDivision of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; ^bCenter for Family and Community Medicine, Karolinska Institute, Huddinge, Sweden

Key Words. Familial risk • Clinical genetic counseling • Referral of familial cancers • Genetic testing • Prevention

Correspondence: Kari Hemminki, M.D., Ph.D., DKFZ Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. Telephone: 49-6221-421800; Fax: 49-6221-421810; e-mail: k.hemminki{at}dkfz.de

Disclosure: No potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Objective. Reliable, clinically useful data on familial risks have not been available for all types of cancer, and familial aggregations of cancers, which are not known to belong to an inherited cancer syndrome, are often overlooked by medical referral systems. We provide uniform data on familial risks in all common cancers.

Methods. The nationwide Swedish Family-Cancer Database includes 11.5 million individuals, born in 1932 and later, along with their parents. Standardized incidence ratios (SIRs) were calculated for age-specific familial risks in offspring.

Results. The familial risks for offspring cancer were increased at 24 of 25 sites when a parent was diagnosed with concordant cancer, at 20 of 24 sites when a sibling was affected, and at 14 of 16 sites when a parent and at least one other sibling were affected. Among the offspring of affected parents, testicular cancer showed the highest risk, 4.52, followed by Hodgkin's disease (3.95) and esophageal cancer (3.36). At many sites, the risks between siblings were higher than those between offspring and affected parents, probably in part because of childhood environmental effects.

Conclusions. The data show convincingly that familial clustering is a common feature for all cancer sites. The results will be helpful in implementing evidence-based guidelines for clinical genetic counseling and in facilitating the recognition of familial risk at all levels of the general medical referral system.