Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor () gene. We review the current literature on this topic, discuss risk of developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H). We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included “EGFR germline” and “familial lung cancer” or “EGFR familial lung cancer”. We also describe our experience of managing a family with rare germline mutant lung cancer. Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months. Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.

中文翻译：

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家族性罕见 EGFR 突变肺癌综合征：R776H 家族的文献回顾和描述

人们对遗传性肺癌的兴趣日益浓厚，特别是表皮生长因子受体 (Epidermal Growth Factor Receptor, ) 基因的种系突变。我们回顾了有关该主题的最新文献，讨论了患肺癌的风险、治疗和筛查方案，并描述了一个患有肺癌的 3 姐妹家庭及其未受影响的母亲，她们都患有罕见的 EGFR 种系突变 (EGFR p.R776H)。我们搜索了 PubMed、Medline、Embase、Cochrane 图书馆、Google Scholar 并扫描了文章的参考列表。搜索词包括“EGFR 种系”和“家族性肺癌”或“EGFR 家族性肺癌”。我们还描述了我们管理患有罕见种系突变肺癌的家庭的经验。尽管数量很少，但文献中描述的案例显示出一些相似之处。患者年龄较轻，通常没有或有轻微吸烟史。 50% 的患者接受酪氨酸激酶抑制剂 (TKI) 治疗，总生存期超过 6 个月。尽管罕见，但种系 p.R776H EGFR 肺癌突变在轻度或从不吸烟的女性患者中所占比例较高，这些患者通常还具有额外的体细胞 EGFR 突变。 TKI 治疗似乎是合适的，但需要进一步研究针对未受影响的携带者或轻度/从不吸烟者的适当筛查方案。