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. 2025 Jul 1;16(1):1229.
doi: 10.1007/s12672-025-03006-z.

Single nucleotide polymorphism and expression of P16 gene as a potential biomarker for oral and pre-oral cancer

Kumud Nigam  1 , Yogendra Verma  2 , Manish Raj Kulshrestha  3 , Aditi Singh  1 , Somali Sanyal  4
Affiliations

Single nucleotide polymorphism and expression of P16 gene as a potential biomarker for oral and pre-oral cancer

Kumud Nigam et al. Discov Oncol. .

Abstract

Objective: 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).

Method: 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.

Results: 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).

Conclusion: 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.

Keywords: P16; OPMD; Oral cancer; Polymorphism.

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Conflict of interest statement

Declarations. Ethical approval: Ethical approval for this study was obtained from the Ethical Committee of King George’s Medical University, Lucknow named as Institutional Ethics Committee (Registration No: ECR/262/Inst/UP/2013) under approval number 85th ECM II B- Ph.D./P2. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Consent to participate: Informed consents (Consent to Participate) were obtained from all participants or, if participants are under 18, from a parent and/or legal guardian. Consent for publication: Consent to Publish were obtained from all participants or, if participants are under 18, from a parent and/or legal guardian. All authors have given their consent to publish this work. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Frequency distributions of different genotypes and allele of p16 450 C > G polymorphism among the subjects of healthy control, OSMF, Lichen planus, leukoplakia and oral cancer
Fig. 2
Fig. 2
Risk of OSMF, Lichenplanus, Leukoplakia and oral cancer with different genotypes and alleles of p16 450 C > G polymorphism. (* p value, 0.05)
Fig. 3
Fig. 3
Level of p16 transcript among the oral cancer, OPMD and healthy control subjects
Fig. 4
Fig. 4
Effect of p16 C > G polymorphism on mRNA secondary structure and corresponding Minimal folding Energy (MFE) predicted by RNAfold
See this image and copyright information in PMC

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