Klinefelter Syndrome and Cancer: A Family Study

The well-established relevance of familial and evidently genetic factors for breast cancer in women may be generalized to all individuals whose chromosome complements include two X chromosomes. Thus, an individual with a masculine phenotype, whose chromosome complement includes a Y chromosome as well as two X chromosomes may face the same risk as his sisters who lack a Y chromosome. The familial (genetic?) factor for cancer diathesis determines a relatively high risk for breast cancer in an individual with two X chromosomes. The familial factor for cancer diathesis is transmitted to and through individuals of both sexes. The usually sex-limited (ie, to females) manifestations of the relevant familial factor is evidently not directly related to gender but rather to interaction with an effect of the occurrence of two X chromosomes. Further medical genetic studies of Klinefelter patients and their families seem warranted in order to better appraise cancer epidemiology. (JAMA 229:809-811, 1974).