Studies on familial clustering of cancer have usually followed transmission of a trait or mutant gene from one parental line. However, an access to families with two affected parents may additionally contribute to the models of carcinogenesis. The combined effect of parental cancer on the cancer risk of the offspring was tested in a large population-based data set. A family-cancer data base was constructed from the nationwide Swedish registries to include over 21,000 cancers in offspring diagnosed at ages 15-51 and their parents. Cancer risk in the offspring was assessed when the parents had different combinations of site-specific cancers. The risk in the offspring was increased only moderately, at most 1.1 times when the father or the mother had cancer. If both parents had cancer the risks were higher and reached statistical significance for the following paternal/maternal site-specific combinations: colorectum/colorectum, prostate/colorectum, colorectum/breast, prostate/breast, melanoma/breast and skin (squamous cell carcinoma)/breast. These results on young and middle-aged adults indicate that cancer in both parents increase cancer risk in the offspring at many sites. A likely molecular explanation is that both parents contribute with different mutant genes to the set of genes constituting the multistage pathway to carcinogenesis.

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