Hospital Sirio Libanes, São Paulo 01308-050, Brazil.
Oncoclínicas, São Paulo 04543-906, Brazil.
Int J Mol Sci. 2023 Oct 10;24(20):15035. doi: 10.3390/ijms242015035.
In southern and southeastern Brazil, the founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs). In the present investigation, we cover clinical and molecular characterizations of lung cancer patients from the Brazilian Li-Fraumeni Syndrome Study (BLISS) database. Among the 175 diagnosed malignant neoplasms, 28 (16%) were classified as LUADs, predominantly occurring in females (68%), aged above 50 years, and never-smokers (78.6%). Significantly, LUADs manifested as the initial clinical presentation of Li-Fraumeni Syndrome in 78.6% of cases. Molecular profiling was available for 20 patients, with 14 (70%) revealing family alterations. In total, 23 alterations in cancer driver genes were identified, comprising 7 actionable mutations and 4 linked to resistance against systemic treatments. In conclusion, the carriers of R337H demonstrate a predisposition to LUAD development. Furthermore, our results indicate that environmental pollution potentially impacts the carcinogenesis of lung tumors in the carriers of R337H.
在巴西南部和东南部，先前有研究记录到 founder 变异 c.1010G>A（R337H）在普通人群中的流行率为 0.3%，与肺腺癌（LUAD）的发病率升高有关。在本研究中，我们对巴西 Li-Fraumeni 综合征研究（BLISS）数据库中的肺癌患者进行了临床和分子特征分析。在诊断出的 175 例恶性肿瘤中，28 例（16%）被归类为 LUAD，主要发生在女性（68%）、年龄在 50 岁以上且从不吸烟（78.6%）的患者中。值得注意的是，78.6%的 LUAD 病例表现为 Li-Fraumeni 综合征的首发临床表现。有 20 名患者可进行分子谱分析，其中 14 名（70%）显示存在家族改变。总共鉴定出 23 个癌症驱动基因的改变，包括 7 个可治疗的突变和 4 个与系统治疗耐药相关的突变。总之，R337H 的携带者易患 LUAD。此外，我们的结果表明，环境污染物可能会影响 R337H 携带者肺肿瘤的癌变。
