The role of hereditary factors in lung cancer is less well understood than in many other human neoplastic diseases. We used a nation-wide family dataset to search for evidence for a genetic predisposition in lung cancer. The Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0-to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age-specific familial risks in offspring by parental or sibling proband, separately. A Kappa test was used to examine the association between familial risk and histology. Compared to the rate of lung cancers among persons without family history, a high risk by parental family history in adenocarcinoma (2.03) and large cell carcinoma (2.14) was found, and only a slightly lower risk was found among patients with squamous cell carcinoma (1.63) and small cell carcinoma (1.55). Among siblings, an increased risk was shown for concordant adenocarcinoma and small cell carcinoma at all ages and for all histological types when cancer was diagnosed before age 50. At young age, risks between siblings were higher than those between offspring and parents. The present data suggest that a large proportion of lung cancers before age 50 years appears to be heri- Lung cancer is the most common fatal cancer in the world, 1,2 and in Sweden it ranks fourth in incidence after prostate, colorectal and squamous cell skin cancer in men and after breast, colorectal and endometrial cancer in women. 3 Cigarette smoking is attributable to approximately 85-90% of all lung cancer, and certain environmental and occupational exposures, such as asbestos and radon, have also been linked to lung cancer development. 4,5 The incidence of lung cancer is rising in women and declining in men as a result of changed smoking behavior. 6 The changing histological patterns in lung cancer probably relate to changes in the composition of cigarettes. 7,8 As only 10% of cigarette smokers develop lung cancer, 9 it is suggested that genetic factors may be a contributing factor. Segregation analysis of lung cancer also supports the existence of heritable effects. 10 -12 In families of smoking probands, the data have suggested Mendelian dominant or codominant effects; in families of nonsmoking probands either no Mendelian or, particularly in lung cancers diagnosed before age 60 years, Mendelian codominant models have provided the best fits.Studies in molecular biology have elucidated the role of genetic factors in modifying an individual's risk for lung cancer. 13,14 There is increasing evidence that genes coding for carcinogen metabolism and DNA repair contribute to familial aggregation of lung cancer. [15][16][17][18] The early reports on genetic influences in lung cancer susceptibility appeared in the early 1980s and showed that firstdegree nonsmoking relatives of lung cancer patients had an increased risk of lung cance...