Abstract
Plasma carcinoembryonic antigen (CEA) levels were studied in 272 members of six pedigrees manifesting the cancer family syndrome and in 191 normal controls. The CEA distributions per se were transformed to square root CEA (√CEA) as a correction for skewness and kurtosis. Duration of smoking and age showed a positive correlation with the level of √CEA in both family members and controls. Distributional features of √CEA among members of the cancer family syndrome pedigrees and the independently sampled controls of the same smoking status did not differ significantly. However, when pedigree data were classified by closeness of relationship to cancer patients there was a significant linear increase in mean √CEA with increasing genetic cancer risk. Surprisingly, unrelated spouses had mean levels of √CEA similar to that for the corresponding risk class of their direct-line mates, and the intraclass correlations of √CEA between direct-line relatives and their spouses approached significance when both spouses were concordant for smoking status. These results suggest the existence of a genetic-connubial effect on plasma CEA levels, presumably due to a common environmental agent acting in concert with the degree of genetic predisposition to cancer. An integrative target cell theory is proposed to explain CEA expressivity in this syndrome. The model involves the interaction of the cancer family syndrome genotype with physical factors (cigarette smoking) and a communicable agent (oncogenic virus).