Genetic predisposition can play an important role in development of lung cancer

December 21, 2004

First-degree relatives of lung cancer patients have a 2 to 3.5 times greater risk of developing lung cancer than the general population, and tobacco smoke plays a major role, even among those with a genetic predisposition, according to a study in the December 22/29 issue of JAMA.

Lung cancer is the leading cause of death from cancer among men and women in many Western countries, according to background information in the article. Death due to lung cancer in the United States exceeds the death rate from breast, prostate, and colon cancer combined. The dominant role of tobacco smoke as a causative factor in lung cancer has been well established. Other studies have indicated that there may be an inherited predisposition to lung cancer, but data have been limited.

Steinn Jonsson, M.D., of the Landspitali-University Hospital, Reykjavík, Iceland, and colleagues examined the contribution of genetic factors to the risk of developing lung cancer in the population of Iceland. The risks for developing lung cancer for first-, second-, and third-degree relatives of patients with lung cancer were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2,756 patients diagnosed with lung cancer within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The risk for smoking was similarly estimated using a random population-based group of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR.

"The nationwide genealogy database used in our study provided a means for uncovering the familial component by revealing more connections between patients, missed in most other populations," the authors write.

The researchers found that a familial factor for lung cancer was shown to extend beyond the nuclear family, as evidenced by significantly increased risks for first-degree relatives (for parents: 2.7 times increased risk; for siblings: 2.02 times increased risk; and for children: 1.96 times increased risk; second-degree relatives (for aunts/uncles: 1.34 times increased risk; and for nieces/nephews: 1.28 times increased risk; and third-degree relatives (for cousins: 1.14 times increased risk) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age 60 or younger at onset) (for parents: 3.48 times increased risk; for siblings: 3.30 times increased risk; and for children: 2.84 times increased risk).

"... this risk ratio [RR] increase in first-degree relatives of patients with lung carcinoma is the result of a combination of environmental, genetic factors, or both. Using genealogy, our study goes further than other reported studies by demonstrating that this familial factor extends beyond the nuclear family as evidenced by significantly increased RR for second- and third-degree relatives of patients with lung carcinoma. In the more distant relationships, shared environmental factors are likely to be of less significance, providing a stronger evidence for genetic factors given that RR is in excess," they write.

"... although the results presented here support a role for genetics in the risk of lung carcinoma, it should be emphasized that tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma," the authors conclude.
-end-
(JAMA. 2004; 292: 2977-2983. Available post-embargo at www.jama.com)

Editor's Note: All the work, data generation, and analysis of this study was supported by deCODE genetics.

The JAMA Network Journals

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