Genetics of Smoking-Related Cancer and Mutagen Sensitivity

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Abstract
Tobacco has central etiologic importance in lung, head and neck, urinary tract, and other cancers. At the same time, risk of these cancers in relatives of affected patients is increased after taking smoking into account, implicating a hereditary component. High-penetrance genes likely explain only a small proportion of familial cases, and thus the specific gene(s) that account for excess risk in relatives for tobacco-related cancers are unknown. Given the evidence for both specific carcinogenic exposures and hereditary influence in the genesis of this class of malignancies, these cancers may offer the best opportunity to unravel a core problem of cancer biology: How do genes and environment act in concert to cause cancer?