Byrjalsen Anna, Garcia Sara L, Borgwardt Line, Wadt Karin, Gerdes Anne Marie, van Overeem Hansen Thomas
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
J Gastrointest Oncol. 2024 Oct 31;15(5):2316-2322. doi: 10.21037/jgo-24-148. Epub 2024 Sep 13.
The occurrence of colorectal cancer (CRC) is increasing among young adults, but the etiology is still largely unknown. In addition to germline monogenetic variants also polygenic risk scores (PRS) have been proven to correctly estimate the risk of CRC.
We present a 24-year-old male with disseminated colon cancer who carried a germline duplication on chromosome 1 spanning 200 kb and covering and parts of and . The duplication was located in tandem. A similar duplication was previously reported in a family with CRC among two brothers aged 52 and 61 years old at diagnosis. Particularly, was an interesting finding as it is involved in the regulation of the Wnt signaling pathway. Disruption of the Wnt pathway is known to cause CRC. However, in our case the duplication did not segregate with disease in the family. Calculation of a PRS in our patient found an average PRS for CRC.
Our findings do not support that this duplication is a monogenetic cause of CRC, nor did a PRS point towards an increased risk in this 24-year-old male. Whether the duplication is a risk factor in combination with other genetic and non-genetic risk factors requires further studies.
结直肠癌（CRC）在年轻成年人中的发病率正在上升，但其病因仍大多未知。除了种系单基因变异外，多基因风险评分（PRS）也已被证明能够正确估计患CRC的风险。
我们报告了一名24岁患有弥漫性结肠癌的男性，其1号染色体上存在一个种系重复，跨度为200 kb，覆盖了 以及 和 的部分区域。该重复呈串联排列。此前在一个CRC家族中报道过类似的重复，该家族中两名兄弟在诊断时年龄分别为52岁和61岁。特别值得一提的是， 是一个有趣的发现，因为它参与Wnt信号通路的调控。已知Wnt通路的破坏会导致CRC。然而，在我们的病例中，该重复在家族中并未与疾病共分离。对我们的患者计算PRS发现其CRC的PRS为平均值。
我们的研究结果不支持该重复是CRC的单基因病因，PRS也未表明该24岁男性的患病风险增加。该重复与其他遗传和非遗传风险因素结合是否为风险因素，需要进一步研究。
