In Reply We appreciate the opportunity to respond to the letters received regarding our article. We have made every effort to thoroughly address the raised questions and comments.

We agree with Beggs that there is no proof that genes such as BRCA1/2, PALB2, CHEK2, and CDKN2A were the driver for these patients’ early-onset colorectal cancers (CRC). The article stated that it was unclear what impact, if any, these mutations had in CRC development, so as to not imply that they were a relevant driver. However, we believe that the findings are important clinically to the patients and their relatives at high risk for the cancers associated with pathogenic germline mutations in these genes. All mutation-positive individuals will need to follow intensive surveillance and prevention options as recommended by the National Comprehensive Cancer Network.¹

作为回复，我们很高兴有机会回复收到的有关我们文章的信件。我们已尽一切努力彻底解决提出的问题和意见。

我们同意 Beggs 的观点，即没有证据表明BRCA1/2、PALB2、CHEK2和CDKN2A等基因是这些患者早发性结直肠癌 (CRC) 的驱动因素。文章指出，尚不清楚这些突变对 CRC 发展有什么影响（如果有的话），因此不暗示它们是相关驱动因素。然而，我们认为这些发现对于与这些基因中的致病性种系突变相关的癌症高危患者及其亲属具有重要的临床意义。所有突变阳性个体都需要遵循国家综合癌症网络建议的强化监测和预防方案。¹