Background: Tobacco smoking is well established as the major etiological factor for lung cancer. In addition, many studies support an approximately two-fold increase in the risk of lung cancer attributable to family history. We examined the incidence of lung cancer among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of male Finnish smokers in order to estimate the risk of lung cancer attributable to having a positive, first-degree family history of the diseaser. Methods: 18,559 men with family history data for cancer were followed for up to 18 years. Relative risks (RR) and 95% confidence intervals (CI) were estimated using proportional hazards models and adjusted for age at randomization, size of sibship, number of cigarettes smoked per day and randomization group. Results: A positive family history of lung cancer was associated with an increased risk of lung cancer (RR=1.48, 95% CI=1.29-1.70), and the risk was greater when participants had two siblings affected (RR=2.53, CI=1.46-4.38). The relative risk associated with a family history of lung cancer increased significantly for each additional brother (but not sister) in the sibship (RR=1.06, CI=1.03-1.09). This increased risk was not explained by heavier smoking, initiation of smoking at an earlier age, or increased exposure to a high-risk occupation of the participants. Earlier ages at diagnosis and moderate smoking habits characterized lung cancer cases with a positive family history of the disease compared to cases with no family history. Conclusions: Our prospective data show that men with a positive family history of lung cancer are significantly more likely to be diagnosed with the disease. In addition, a significant relative risk due to larger sibships, and to larger numbers of brothers, was identified.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA