MICA A5.1 homozygous genotype is associated with a risk for early-onset oral cancer
MICA A5.1 homozygous genotype is associated with a risk for early-onset oral cancer
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DOI：
10.1016/j.oraloncology.2021.105256
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发表时间：
2021-03-14
期刊：
影响因子：
4.8
通讯作者：
Okamoto, Tetsuji
中科院分区：
文献类型：
--
作者：
Tani, Ryouji;Ito, Nanako;Okamoto, Tetsuji
目的：据报道，遗传易感性与早发性口腔癌有关，尽管这种癌症的遗传基础尚不清楚。主要组织相容性复合物I类相关链A（云母）通过激活自然杀伤（NK）受体NKG2D在消除恶性肿瘤中起着至关重要的作用。云母多态性可能影响其与NKG2D的结合。我们的目的是发现云母基因微卫星多态性是否与日本人群口腔鳞状细胞癌（OSCC）的发生有关。材料和方法：我们收集了386例口腔鳞癌患者和103名健康对照者。通过PCR分析基因组DNA中云母基因跨膜区的微卫星重复多态性。比较各组的各种等位基因的患病率及其与疾病预后和生存率的关系。结果如下：我们发现患有口腔鳞癌的青少年和年轻人（AYA）比健康对照更可能具有云母A5.1纯合基因型（P = 0.0001），但其生存率高于其他云母基因型（P = 0.0185）。结论：云母不能激活NK细胞，促进了肿瘤的免疫逃逸。云母A5.1纯合性在个体对OSCC的易感性中起作用，增加早发性口腔癌的风险。然而，这样的患者比具有其他云母基因型的患者具有更好的预后。
Objectives: Genetic predisposition is reportedly involved in early-onset oral cancer, although the genetic basis of this cancer remains unclear. The major histocompatibility complex class I-related chain A (MICA) plays a crucial role in eliminating malignant tumors by activating NKG2D, the natural killer (NK) receptor. MICA polymorphism might affect its binding to NKG2D. We aimed to find whether MICA gene microsatellite polymorphism is involved in the risk of oral squamous cell carcinoma (OSCC) development in a Japanese population. Materials and methods: We recruited 386 patients with OSCC and 103 healthy controls. Genomic DNA was analyzed by PCR for microsatellite repeat polymorphism in the transmembrane region of the MICA gene. The groups were compared for the prevalence of various alleles and their association with disease prognosis and survival. Results: We found that adolescents and young adults (AYA) with OSCC were more likely to have the MICA A5.1 homozygous genotype than healthy controls (P = 0.0001), but their survival rate was higher than with other MICA genotypes (P = 0.0185). Conclusion: These results suggest that cancer's immune escape is facilitated by MICA's failure to activate the NK cells. MICA A5.1 homozygosity plays a role in individual susceptibility to OSCC, increasing the risk of early-onset oral cancer. However, such patients have a better prognosis than those with other MICA genotypes.