Wu P-F, Lee C-H, Wang M-J, Goggins W B, Chiang T-A, Huang M-S, Ko Y-C
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, ROC.
Eur J Cancer. 2004 Jan;40(2):260-6. doi: 10.1016/j.ejca.2003.08.021.
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 non-smoking 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.
以往的研究发现，有一位患肺癌的一级血亲是肺癌风险的一个可能预测因素，但一些研究表明，这种关联不显著，或者仅在部分研究人群中显著。为了确定家族聚集性以及是否有证据表明存在一个控制女性非吸烟者患肺癌易感性的基因，在一项基于人群的病例对照研究中，使用来自216名女性非吸烟肺癌先证者（2328人）的数据，进行了估计协变量效应的多重逻辑回归方法和最大似然分离分析。结果发现，肺癌家族史是非吸烟女性患肺癌的一个显著预测因素（调整后的优势比（OR）=5.7，95%置信区间（CI）=1.9-16.9）。与有患肺癌的男性亲属相比，有患肺癌的女性亲属与肺癌风险的关联更强（调整后的OR=14.4，95%CI=2.7-75.5）。这种关联在发病年龄小于60岁的先证者中更强（调整后的OR=11.2，95%CI=2.2-56.9）。所有孟德尔模型对数据的拟合都明显优于散发性（无主要类型）模型或环境模型（P<0.001）。孟德尔共显性模型对早发先证者的数据拟合最佳，并且显示出对非吸烟肺癌先证者的主要易感基因座有更强的影响。本研究结果提供了证据，表明一个罕见的常染色体共显性基因可能影响非吸烟者患肺癌的风险，并导致在非吸烟肺癌患者中观察到的家族聚集性。
