Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan

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 populationbased 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< 0.00l). 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. # 2003 Elsevier Ltd. All rights reserved.