Previous studies have found that having a first-degree blood relative with lung cancer was a possible predictor of lung cancer risk, but some studies have indicated that the association is non-significant or only significant for a subset of the studied population. To determine the familial aggregation and whether there is any evidence for a gene controlling the susceptibility to developing lung cancer in female non-smokers, multiple logistic regression methods for estimating covariate effects and maximum likelihood segregation analyses were performed using data from 216 female non-smoking lung cancer probands (2328 individuals) in a population-based case-control study. Having a family history of lung cancer was found to be a significant predictor of lung cancer for nonsmoking females (Adjusted Odds Ratio (OR) = 5.7, 95% Confidence Interval (CI) = 1.9-16.9). Having a female relative with lung cancer (adjusted OR = 14.4, 95% CI = 2.7-75.5) was more strongly associated with the lung cancer risk than was having a male relative with lung cancer. This association was stronger for probands aged less than 60 years at onset (adjusted OR = 11.2, 95% CI = 2.2-56.9). All of the Mendelian models fitted the data significantly better than the sporadic (no major type) model or the environmental model (P < 0.001). The Mendelian codominant models provided the best fit of the data for the early onset probands and showed a stronger effect for a major susceptibility locus for non-smoking lung cancer probands. The results of this study provide evidence that a rare autosomal codominant gene may influence the risk lung cancer in non-smoker and is responsible for the familial aggregation observed in non-smoking lung cancer patients. (C) 2003 Elsevier Ltd. All rights reserved.
