头颈部鳞状细胞癌（HNSCC）通常与烟草消费、酗酒或两者都有关。黏蛋白（MUCs）是许多上皮组织产生的高分子量糖蛋白。许多研究表明，MUCs在癌症转移中发挥重要作用。已观察到MUC6在胃和增生性表型中的表达，并在癌症进展过程中起重要作用。我们发现亚洲HNSCC患者的MUC6水平较低，影响了HNSCC患者的无疾病生存。接下来，我们研究了MUC6多态性和环境致癌物暴露对HNSCC易感性和临床病理特征的联合效应。使用实时PCR分析了MUC6的三个单核苷酸多态性（SNP）（rs7481521、rs6597947和rs61869016）。在调整其他协变量后，我们发现，在非咀嚼槟榔的人群中，携带MUC6 rs6597947位点的CC基因型比野生型携带者更少患口腔鳞状细胞癌（OSCC）的风险。此外，携带MUC6 rs6597947位点的AA + CC基因型的男性口腔癌患者比其他基因型具有较低的淋巴结转移风险，表明存在重要的功能损害和失代偿性疾病。因此，我们的研究发现表明MUC6的遗传变异可能与OSCC相关，并提示OSCC患者的进展。© 2023作者。细胞与分子医学杂志由细胞与分子医学基金会和约翰威利·爱尔克有限公司出版。

Head and neck squamous cell carcinomas (HNSCCs) are generally associated with tobacco consumption, alcohol abuse or both. Mucins (MUCs) are high-molecular-weight glycoproteins produced by many epithelial tissues. Many studies have indicated that MUCs play an important role in cancer metastasis. MUC6 expression has been observed in gastric and oncocytic phenotypes and plays an important role during cancer progression. We found that levels of MUC6 are lower in Asian HNCC patients and affect the disease-free survival of HNCC patients. Next, we investigated the combined effect of MUC6 polymorphisms and exposure to environmental carcinogens on the susceptibility to and clinicopathological characteristics of HNCC. Three single-nucleotide polymorphisms (SNPs) of MUC6 (rs7481521, rs6597947 and rs61869016) were analysed using real-time PCR. After adjusting for other co-variants, we found that carrying a CC genotype at MUC6 rs6597947 led to a lower risk of developing oral squamous cell carcinoma (OSCC) than wild-type carriers among non-betel-quid chewers. Moreover, male oral cancer patients who carried the AA + CC genotype at MUC6 rs6597947 had a lower risk of lymph node metastasis than other genotypes, suggesting a significant functional compromise and decompensated disease. Therefore, our findings suggest that genetic variations in MUC6 may correlate to OSCC and indicate the progression in OSCC patients.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.