Nigam Kumud, Verma Yogendra, Kulshrestha Manish Raj, Singh Aditi, Sanyal Somali
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Gomti Nagar Ext. Lucknow, Lucknow, 226028, India.
Department of Oral Pathology, King George's Medical University, Lucknow, India.
Discov Oncol. 2025 Jul 1;16(1):1229. doi: 10.1007/s12672-025-03006-z.
This study investigated the association between p16 gene and its 450 C > G (rs11515) polymorphism with risk of oral cancer and precancerous oral lesions/oral potentially malignant disorder (OPMD).
The study included 230 individuals with OPMD conditions (70 with leukoplakia, 90 with oral submucous fibrosis, and 70 with lichen planus), 72 oral cancer patients, and 300 cancer-free healthy controls. Genotyping of the p16 450 C > G polymorphism was conducted using PCR-RFLP methods, and genotype and allele frequencies were analyzed using chi-square test. Additionally, p16 gene expression levels were measured using RT-PCR among oral cancer patients, those with OPMD, and healthy controls. RNA fold was used to calculate the MFE of p16 mRNA.
The findings revealed that G allele of p16 450 C > G polymorphism significantly increased risk of oral diseases (oral cancer and OPMD) compared to C allele (OR 1.67, p = 0.0001). GG genotype was associated with higher risk of oral submucous fibrosis (OR 4.63, p = 0.0001), lichenplanus (OR 3.93, p = 0.0002), and leukoplakia (OR 2.38, p = 0.02) compared to CC genotype. Smokers and tobacco chewers carrying the G allele were at a significantly increased risk of developing OPMD (OR = 3.78 and 2.89). Notably, p16 transcript expression was significantly elevated (13.56-fold) in oral cancer patients compared to healthy controls. According to insilco analysis G allele gives more stable transcript of p16 (MEF - 64.90 kcal/mol) compared to C allele (MFE - 61.70 kcal/mol).
These findings suggest that p16 gene and its 450 C > G polymorphism may be associated with risk of oral diseases, indicating their potential utility as biomarkers for these conditions.
本研究调查p16基因及其450 C＞G（rs11515）多态性与口腔癌及癌前口腔病变/口腔潜在恶性疾病（OPMD）风险之间的关联。
该研究纳入230例OPMD患者（70例白斑患者、90例口腔黏膜下纤维化患者和70例扁平苔藓患者）、72例口腔癌患者以及300例无癌健康对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对p16 450 C＞G多态性进行基因分型，并使用卡方检验分析基因型和等位基因频率。此外，采用逆转录-聚合酶链反应（RT-PCR）测定口腔癌患者、OPMD患者及健康对照中p16基因的表达水平。使用RNA折叠法计算p16 mRNA的最小自由能（MFE）。
研究结果显示，与C等位基因相比，p16 450 C＞G多态性的G等位基因显著增加口腔疾病（口腔癌和OPMD）风险（比值比[OR]为1.67，p = 0.0001）。与CC基因型相比，GG基因型与口腔黏膜下纤维化（OR为4.63，p = 0.0001）、扁平苔藓（OR为3.93，p = 0.0002）和白斑（OR为2.38，p = 0.02）的较高风险相关。携带G等位基因的吸烟者和嚼烟者发生OPMD的风险显著增加（OR分别为3.78和2.89）。值得注意的是，与健康对照相比，口腔癌患者中p16转录本表达显著升高（13.56倍）。根据在线分析，与C等位基因（MFE为-61.70千卡/摩尔）相比，G等位基因产生的p16转录本更稳定（MFE为-64.90千卡/摩尔）。
这些发现表明，p16基因及其450 C＞G多态性可能与口腔疾病风险相关，表明它们作为这些疾病生物标志物的潜在效用。
