The genetics of tobacco-induced malignancy.

Abstract

Several areas of investigation contribute to an increasing understanding of the genetics of malignancies associated with tobacco use. While the strong influence of tobacco exposure on cancer development obscures genetic influences, there are indications that aspects of cancer susceptibility may have a heritable basis. In addition, specific sites within the genome appear to be commonly involved in these malignancies. This review describes research relevant to investigation of the genetics of tobacco-induced malignancy. A review of the pertinent literature covered the past 20 years. References were gleaned from a variety of sources including manual review of the most recent journals, a computerized database (Mini-MEDLINE), references cited in previous works, and our own ongoing research in cancer genetics and molecular biology. Whenever possible, controlled studies from peer-reviewed journals were used. Where studies have shown conflicting results, the possible confounding factors are discussed. From a broad array of research areas, a view of the genetic aspects of tobacco carcinogenesis emerges. This includes syndromic and nonsyndromic susceptibility, genetic determinants of carcinogen metabolism, DNA adduct formation, and site-specific genetic alterations in tobacco-induced malignancy. In addition to specific gene alterations commonly seen in tobacco-induced malignancy, viral infections may contribute to cancer development through pathways related to tobacco carcinogenesis. Further research on many aspects of tobacco-induced carcinogenesis is warranted. Investigation of cancer susceptibility may contribute to understanding DNA surveillance and repair pathways. Carcinogen metabolism investigations have application in cancer detection and prevention schemes. Further understanding of tumor suppressor gene function and the role of gene amplification in carcinogenesis may allow design of gene-specific strategies in cancer treatment.