Division of Thoracic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
Division of Medical Oncology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah; Huntsman Cancer Institute, Salt Lake City, Utah.
J Thorac Oncol. 2018 Jul;13(7):938-945. doi: 10.1016/j.jtho.2018.03.024. Epub 2018 Apr 4.
Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologic subtypes is unknown.
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.
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.
This analysis supports a genetic predisposition to lung cancer carcinogenesis in nonsmokers with nonsquamous NSCLC.
肺癌的发生强烈受到环境和遗传因素的影响。不同组织学亚型的遗传贡献尚不清楚。
分析了基于人群的计算机化家谱资源与全州肺癌病例癌症登记处（N=5408）的关联，以评估吸烟者（n=1751）和不吸烟者（n=818）中肺癌组织学亚型的遗传贡献。使用统计方法来检验肺癌病例是否存在显著的亲缘关系过剩。
除小细胞肺癌亚组（p=0.213）外，所有分析的肺癌组织学亚组均观察到显著的远亲关系过剩。当考虑吸烟者和肺癌非吸烟者的组织学亚组时，仅在非吸烟者的非小细胞肺癌（n=653[p=0.026]）中观察到亲缘关系过剩，特别是在非鳞状组织学亚型的非吸烟者中（n=561[p=0.036]）。总共确定了 61 个家族，这些家族在非吸烟者中表现出非鳞状非小细胞肺癌的显著高风险，并且在具有这些高风险家族的个体中观察到女性病例过多。
这项分析支持非鳞状非小细胞肺癌的非吸烟者肺癌发生存在遗传易感性。
