Introduction: Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologic subtypes is unknown. Methods: A population‐based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (N = 5408) was analyzed to evaluate the heritable contribution to lung cancer histologic subtype in smokers (n = 1751) and nonsmokers (n = 818). Statistical methods were used to test for significant excess relatedness of lung cancer cases. Results: Significant excess distant relatedness was observed for all lung cancer histologic subgroups analyzed except for the SCLC subset (p = 0.213). When histologic subsets of smokers and nonsmokers with lung cancer were considered, excess relatedness was observed only in nonsmokers with NSCLC (n = 653 [p = 0.026]) and, in particular, in those nonsmokers with the nonsquamous histologic subtype (n = 561 [p = 0.036]). A total of 61 pedigrees demonstrating a significant excess risk of nonsquamous lung cancer in nonsmokers were identified, and an excess of cases in females was observed among the individuals with these high‐risk pedigrees. Conclusions: This analysis supports a genetic predisposition to lung cancer carcinogenesis in nonsmokers with nonsquamous NSCLC.

中文翻译：

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非吸烟者非鳞状非小细胞肺癌的遗传贡献

简介：肺癌的发生受到环境和遗传因素的强烈影响。对不同组织学亚型的遗传贡献尚不清楚。方法：分析了与全州肺癌病例（N = 5408）相关的基于人群的计算机化谱系资源，以评估吸烟者（n = 1751）和非吸烟者（n = 818）肺癌组织学亚型的遗传贡献. 统计方法用于检验肺癌病例的显着过度相关性。结果：对于所有分析的肺癌组织学亚组，除了 SCLC 亚组（p = 0.213）外，均观察到显着的过度远缘相关性。当考虑吸烟者和非吸烟者肺癌的组织学亚组时，仅在非吸烟者与非小细胞肺癌（n = 653 [p = 0.026]）中观察到过度相关性，并且，特别是，在那些具有非鳞状组织学亚型的非吸烟者中（n = 561 [p = 0.036]）。共有 61 个谱系证明非吸烟者患非鳞状肺癌的风险显着增加，并且在具有这些高风险谱系的个体中观察到女性病例过多。结论：该分析支持非鳞状 NSCLC 的非吸烟者肺癌发生的遗传易感性。