December 22, 2004

Smoking plays a dominant role in the development of the disease, but genetic factors appear to establish increased susceptibility that goes beyond the nuclear family

In a paper published today in the Journal of the American Medical Association (JAMA), deCODE scientists and colleagues from Iceland’s National-University Hospital and the Icelandic Heart Association present the results of a major population-based study of the familial risk for lung cancer; the most common cause of death from cancer in the industrialized world. The study points to the existence of genetic factors that contribute to the disease, even after taking the familiality of smoking into account, suggesting that lung cancer can be viewed as a disease in which a single environmental factor, tobacco smoke, can turn a genetic predisposition into disease. The study, entitled “Familial risk of lung carcinoma in the Icelandic population,” appears in the December 22nd edition of JAMA and in the online edition of the journal.

The study analyzes the Icelandic Cancer Registry’s comprehensive data on the occurrence of lung cancer in Iceland from 1955 to 2002 in the context of deCODE’s nationwide genealogical data. The results demonstrate that even cousins of those who have been diagnosed with lung cancer are at a significantly higher risk of developing the disease than are members of the population at large. This increased risk is particularly notable in relatives of patients diagnosed with the disease before the age of 60, suggesting that the genetic factors play a larger role in early-onset forms of the disease. Spouses of patients are also shown to be at a significantly increased risk of developing the disease, underscoring the very powerful role of environmental and behavioral factors, most notably smoking.

Because the role of smoking is so fundamental, the authors addressed the question of whether the familiality of smoking and/or nicotine addiction alone was strong enough to explain the familiality of lung cancer. Using population-based data from an ongoing, longitudinal survey of health, behavior and disease being carried out by the Icelandic Heart Association, the authors examined the familial risk of smoking in Iceland. Since the familial risk of lung cancer was higher than the familial risk for smoking – even beyond the nuclear family – the authors conclude that there are indeed genetic factors that contribute significantly to the likelihood of developing lung cancer, and most particularly in early-onset forms of the disease.

These findings suggest that the identification of the genes involved might enable the development of better means of treatment, and also of developing diagnostic tests that could identify those who are at a particularly high risk of the disease. The authors conclude by reiterating that the role of smoking in lung cancer cannot be overemphasized – it is the dominant factor in the pathogenesis of the disease, even among those who are genetically predisposed.