Promoter Methylation and Relative mRNA Expression of the p16 Gene in Cervical Cancer in North Indians

Abstract

<span style="text-decoration: underline;"><span style="font-size: small;">Background</span></span><span style="font-size: small;">: Cervical carcinoma is one of the main causes of mortality in women worldwide as well as in India. It occurs as a result of various molecular events that develop from the combined influences of an individual's genetic predisposition and external agents such as smoking and menstrual hygiene, for example. However, infection with human papillomavirus (HPV) is the established major risk factor. The aim of the current study was to investigate p16 CpG island methylation and establish any correlation with mRNA expression in north Indian population. <span style="text-decoration: underline;">Materials and Methods</span>: We analyzed 196 woman volunteer out of which 98 were cases and 98 healthy controls. For the analysis of methylation pattern, DNA extracted from blood samples was modified with a bisulfate kit and used as template for methylation specific PCR (MSP). Quantitative real-time PCR (QRT-PCR) was performed to check mRNA expression. <span style="text-decoration: underline;">Results</span>: Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer. We analyzed methylation pattern and found 60.3% methylation in cases with low mRNA expression level (0.014) as compare to controls (1.24). It was also observed that promoter methylation of p16 gene was significantly greater in FIGO stage III. <span style="text-decoration: underline;">Conclusions</span>: We conclude that p16 methylation plays an important role in cervical cancer in the north Indian population and its methylation decreases mRNA expression. It can b e used as an important and consistent blood biomarker in cervical cancer patients. </span>