Genetics and smoking-associated cancers. A study of 485 families

Cancer risk was evaluated in relatives of 254 consecutively ascertained probands with histologically verified lung cancer, and 231 probands with other smoking-related cancers. Findings disclosed a lack of any strong evidence for increased risk in lung cancer per se when only lung cancer in relatives was considered. Confounding factors, most prominent of which was the effect of cigarette smoking, variation of secular trends, and the heritability of the smoking phenotype itself, tended to obfuscate identification of an inherited effect presenting itself exclusively as lung cancer liability. On the other hand, a significant increase was observed in cancers of all anatomic sites among the relatives of lung cancer probands (P less than 0.001). Most of these neoplastic lesions were not associated with smoking and were not greatly influenced by secular trends. Furthermore, no significant excesses of cancer at all anatomic sites in relatives of probands with other smoking-associated carcinomas were observed. Thus, it may be concluded that the observation of increased risk for cancer at all anatomic sites in relatives of lung cancer probands may be a reflection of an underlying susceptibility to malignancy in these families.