Epigenetic Silencing of p16INK4a gene in Sporadic Breast Cancer

Satya P Singh; Mallika Tewari; Alok K Singh; Raghvendra R Mishra; Hari S Shukla

doi:10.1007/s13193-023-01780-2

Epigenetic Silencing of p16INK4a gene in Sporadic Breast Cancer

Indian J Surg Oncol. 2023 Dec;14(4):822-828. doi: 10.1007/s13193-023-01780-2. Epub 2023 Jun 20.

Authors

Satya P Singh¹, Mallika Tewari¹, Alok K Singh², Raghvendra R Mishra³, Hari S Shukla¹

Affiliations

¹ Department of Surgical Oncology, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India 221005.
² Department of Geriatric Medicine, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India 221005.
³ Medical Lab Technology, DDU Kaushal Kendra, Banaras Hindu University, Varanasi, India.

PMID: 38187858
PMCID: PMC10766924 (available on 2024-12-01)
DOI: 10.1007/s13193-023-01780-2

Abstract

Epigenetic alterations of tumor suppressor genes (TSG) involved in the onset and progression of Breast Cancer (BC) may serve as biomarkers for early detection and prediction of disease prognosis. We have herein tried to determine the methylation status of TSG, p16INK4a, in our 50 BC patients and their association with clinicopathological parameters. The methylation status of the p16INK4a gene in fresh tissue samples from 50 patients with BC was assessed by methylation-specific polymerase chain reaction (MS-PCR). The mean age of BC patients was 49.30 ± 9.75 years. Of 50 BC samples tested, 21 (42%) had methylated p16INK4a gene. p16INK4a gene hypermethylation was significantly associated with age ≤ 50 years, premenopausal status and advanced BC stage. Multivariate analysis revealed a strong association between advanced BC stage (Stage III and Stage IV) and p16INK4a hypermethylation (P = 0.008, RR = 5.996, 95% CI = 1.581-22.739). p16INK4a methylation was significantly associated with Triple Negative BC (TNBC) (P = 0.045, OR = 4.181, 95% CI = 1.030-16.981). These findings indicate that p16INK4a hypermethylation frequently occurs in BC. Hypermethylation of p16INK4a in young, premenopausal, TNBC and with advance stage in BC patients suggests its association with aggressive BC.

Keywords: Breast Cancer; Epigenetics; Hypermethylation; Tumor suppressor genes; p16INK4a.

© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.