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Previous studies of the genetic epidemiology of lung cancer have suggested a modest (twofold) increased risk associated with a family history of lung cancer. It has been unclear whether the increased risk observed reflected genetic factors specific to lung cancer, genetic modifiers of nicotine addiction (leading to increased tobacco exposure), or shared environmental factors.
Jonsson and colleagues accessed the Icelandic genealogical database (which has population and ancestry data for all Icelanders), the Icelandic Cancer Registry (to identify cases of lung cancer), and the Reykjavik Heart Study (which provided smoking information for a cohort of the studied patients). They found a significant (2–3.5 fold) increased risk of developing lung carcinoma in first degree relatives of patients with lung cancer. This relative risk exceeded the relative risk of smoking.
An increased relative risk of lung cancer was also seen in the second and third degree relatives of probands, again in excess of the relative risk of smoking. Spouses of patients had a slightly increased risk of developing lung cancer but this appears to relate to a common environment; their relative risk of smoking exceeded that of lung cancer.
By controlling for tobacco exposure and demonstrating a rise in relative risk beyond the nuclear family, the investigators present compelling evidence for the existence of specific inherited genetic factors which can contribute to the development of lung cancer. Further studies may outline inheritance patterns and point towards specific gene defects or polymorphisms responsible for the familial association found.
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