Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Clin Breast Cancer. 2021 Jun;21(3):218-230.e6. doi: 10.1016/j.clbc.2020.09.001. Epub 2020 Sep 6.
Breast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk.
Thirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups.
Estrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer.
The decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.
乳腺癌幸存者发生无关原发性癌症（尤其是肺癌）的风险增加。有证据表明，性激素以及 DNA 修复途径的失调可能导致肺癌的发生。我们研究了激素状态以及与 DNA 修复（BRCA1/2、ERCC1 和 P53R2）、合成（TS 和 RRM1）和细胞分裂（TUBB3）相关的标志物的表达是否与肺癌风险相关。
招募了 37 名患有无关性肺癌的乳腺癌幸存者和 84 名对照组患者，其中包括乳腺癌（42/84）或肺癌（42/84）患者。对肿瘤组织进行了免疫组织化学检测。使用几何均数比来评估标志物水平与患者群体之间的关联。
雌激素受体在大约 90%的乳腺癌组中表达，但在大多数肺癌组中呈阴性，这与肺癌对照组的结果相似。同样，肺癌组中 ER 同工型β的表达较弱。与对照组相比，乳腺癌患者的 BRCA1、P53R2 和 TUBB3 蛋白分析表达水平显著降低。同样，在先前接受过乳腺癌放疗的肺癌患者中观察到 BRCA1 减少，同时 BRCA2 增加。此外，在先前接受过乳腺癌放疗的女性的同侧肺癌中，BRCA2 和 TUBB3 增加。
乳腺癌中 DNA 修复蛋白的减少可能使这些女性更容易受到治疗相关癌症的影响。先前接受过乳腺癌放疗的患者肺癌中 BRCA2 和 TUBB3 的增加可能反映了组织对电离辐射暴露的反应。
