Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Cancer Epidemiol Biomarkers Prev. 2020 Dec;29(12):2719-2728. doi: 10.1158/1055-9965.EPI-20-0714. Epub 2020 Oct 2.
High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4 T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis.
In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC).
A significant association of the SNP rs7524066 with more favorable colorectal cancer-specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74-0.94; value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68-0.98; value: 0.03). Suggestive evidence for association was found with two SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed.
Common genetic variation in the Treg pathway implicating genes such as and was shown to be associated with prognosis of colorectal cancer patients.
The implicated genes warrant further investigation.
肿瘤组织中存在大量淋巴细胞，包括 T 调节细胞（Treg），与结直肠癌的生存预后较好相关。Treg 是 CD4+T 淋巴细胞的一个亚群，是癌症中免疫抑制的介质，因此与 Treg 分化和功能相关的基因变异可能与结直肠癌的预后相关。
在一个前瞻性的德国结直肠癌患者队列中，我们使用 Cox 回归模型评估了 58 个 Treg 相关基因中的 771 个单核苷酸多态性（SNP）与总生存期和结直肠癌特异性生存期的相关性。还研究了微卫星不稳定性（MSI）状态的修饰作用，因为具有 MSI 的肿瘤具有更多的淋巴细胞浸润，与更好的预后相关。在国际结直肠癌生存分析联盟（ISACC）的 2047 例结直肠癌患者中尝试了对显著结果的复制。
SNP rs7524066 与结直肠癌特异性生存期相关，携带较少等位基因的患者具有更好的预后[风险比（HR）每少一个等位基因：0.83；95%置信区间（CI），0.74-0.94； 值：0.0033]，在 ISACC 中得到了复制（HR：0.82；95% CI，0.68-0.98； 值：0.03）。发现 rs16906568 和 rs7845577 两个 SNP 存在相关性的迹象。在发现分析中，根据 MSI 与总生存期有差异相关性的 13 个 SNP 没有得到证实。
Treg 途径中的常见遗传变异，涉及 等基因，与结直肠癌患者的预后相关。
所涉及的基因值得进一步研究。
