Familial risks of cancer as a guide to gene identification and mode of inheritance

Occurrence of cancer in parents and offspring may be due to dominant causes, whereas cancer affecting only siblings may indicate a recessive causation. Systematic comparisons of mode of inheritance have not been available for most types of cancer. Using the Swedish Family-Cancer Database, standardized incidence ratios (SIR) were calculated for offspring whose parents or siblings were diagnosed with the same cancer. The degree of environmental causation was assessed by spouse correlation and by comparing risks among siblings of different ages. We identified reliable familial risks for all common neoplasms, SIRs ranging from 1.6 to 4.3 when only a parent was affected and up to 8.5 when only a sibling was effected. Risks between siblings were particularly high for renal cancer. Spouse correlation was found only for lung and stomach cancer, but the analysis of sibling risks by their age difference suggested that even for some other cancers environmental effects in childhood may contribute to familial aggregation. The results from these analysis suggest that familial cluster of cancer at most sites is heritable, caused by dominant effects; for renal cancer recessive effects may be most important. (C) 2004 Wiley-Liss, Inc.