By Alfred G. Knudson Jr. (auth.), Harry Harris, Kurt Hirschhorn (eds.)
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Extra info for Advances in Human Genetics 8
24,63 In reviewing the whole problem of genetic predisposition to lung cancer, Mulvihill218 has raised the possibility that pulmonary fibrosis and lung cancer may be associated via a genetic predisposition to scleroderma. This association could also be mediated via a heritable immunological abnormality, especially in view of the occurrence of two cases of lung cancer in a pedigree afflicted with lymphoproliferative disorders. 91 ,218 It seems that lung cancer may well occur in four groups of individuals: (1) a genetically predisposed group in which environmental variation plays a negligible role, as in hereditary pulmonary fibrosis; (2) a group in which an environmental factor, such as smoking, operates without any genetic susceptibility; (3) a group in which both genetic and environmental factors operate, possibly exemplified by aryl hydrocarbon hydroxylase activity and smoking; and (4) a group to which neither genetic nor environmental variation contributes, but in which spontaneous mutations may dominate.
In addition, Lynch et al. 184 have called attention to families in which endometrial cancer is the principal tumor, although cancer can occur at other sites too. These pedigrees are consistent with dominant inheritance. Some families in this group show a high association of this cancer with obesity, hypertension, and diabetes mellitus. 22,184 A stigmatizing condition associated with endometrial cancer is the Stein-Leventhal syndrom~, an endocrine dysplasia characterized by amenorrhea, sterility, hirsutism, obesity, and ovarian cystS.
A second class of genetic predisposition could involve genetic control of the conversion of a noncarcinogenic environmental agent into a carcinogen. Such a genetic control is known to occur in mice with respect to the enzyme aryl hydrocarbon hydroxylase, which catalyzes the conversion of many chemical "carcinogens" from an inactive proximal state to an active ultimate state. 223 An unconfirmed report indicates that a genetic polymorphism exists for this enzyme in man, and that smokers with high or intermediate inducibility are much more likely to develop lung cancer than are smokers with low inducibility.
Advances in Human Genetics 8 by Alfred G. Knudson Jr. (auth.), Harry Harris, Kurt Hirschhorn (eds.)