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December 22/29, 2004

Lung Cancer Etiology: Independent and Joint Effects of Genetics, Tobacco, and Arsenic

Author Affiliations

Author Affiliations: Department of Epidemiology, Mailman School of Public Health and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY (Dr Ahsan); and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (Dr Thomas).

JAMA. 2004;292(24):3026-3029. doi:10.1001/jama.292.24.3026

Lung cancer is the number one neoplasm in the world, both in terms of incidence and mortality.1 The incidence of lung cancer differs by geographic area, sex, age, and over time,1,2 reflecting the effect of the underlying distribution and trend in use of its principal determinant, tobacco smoking. Although 80% to 90% of lung cancer cases occur in current or past tobacco smokers, only a small fraction of smokers (1%-15%) develop lung cancer,2 depending on how much and how long an individual has smoked and the presence of other causes of lung cancer. Clearly, because all lung cancers do not occur in smokers and the vast majority of smokers do not develop lung cancer, other etiological factors can independently (in the absence of smoking) or jointly (in conjunction with smoking) cause lung cancer, beyond the purely stochastic nature of the disease process. These factors include genetics (measured as family history),3,4 arsenic exposure,5-8 radiation exposure, and other environmental carcinogens.2 Although genetic factors probably contribute in all populations, the contribution of other factors is population-specific. For example, in all areas of the world lung cancer shows a modest level of familial aggregation,2,9-12 whereas only in specific environmental, occupational, and therapeutic settings do arsenic and ionizing radiation contribute to lung cancer etiology.2