%0 Journal Article
%T Aberrant Methylation in Promoters of GSTP1, p16, p14, and RASSF1A Genes in Smokers of North India
%A Jagdeep S. Deep
%A Sukhjeet Sidhu
%A Avinash Chandel
%A Shruti Thapliyal
%A Charu Garg
%J ISRN Pulmonology
%D 2012
%R 10.5402/2012/247631
%X Promoter hypermethylation plays an important role in the inactivation of tumor suppressor/metabolic genes during tumorigenesis. The screening of high-risk population (smokers) for hypermethylation pattern in tumor suppressor/metabolic genes can be a good noninvasive biomarker tool, which should be included in prognosis so that therapeutic measures can be initiated at an early stage. The purpose of this study was to determine the prevalence of aberrant promoter methylation of GSTP1, p16, p14, and RASSF1A genes in smokers and nonsmokers of North India. Our study showed that compared with nonsmokers, smokers have an increased risk of hypermethylation in these genes. We found that 57.3% of the smokers samples showed methylation for GSTP1, 38% for p16, 18% for p14, and 32% for RASSF1A. Our population study allowed us to reveal the relationship between smoking and the subsequent appearance of an epigenetic change. Smoking speeds up the hypermethylation of these genes, which are thus unable to express, making the person more susceptible to the risk of lung and other solid carcinomas. Hypermethylation studies on DNA from two lung cancer cell lines (A549 and H460) were also done to compare the results, and the results are similar to samples of smokers. 1. Introduction Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. The most commonly diagnosed cancers worldwide are lung followed by breast and colorectal cancers. Lung cancer is the most common cause of cancer-related mortality worldwide. About 1,80000 new cases are detected every year [1, 2]. Because of its high fatality (the ratio of mortality to incidence is 0.86) and the lack of variability in survival, in developed and developing countries, the highest and lowest mortality rates are estimated in the same regions, both in men and women. The large number of fatalities illustrates the lack of effective therapeutic alterations for a disease which is mostly diagnosed at an advanced stage [3]. There is a strong need for the development of biomarkers [4¨C6] that can spot this disease at an early stage which in turn would improve the survival rates. In comparison to mRNA, miRNA, and certain proteins, the use of genomic DNA methylation as biomarker has some novel attractions. Firstly, genomic DNA is highly stable, easy to extract, and secondly it can survive harsh conditions [7]. Genomic DNA has received special attention because of its potential application as a noninvasive, rapid, and sensitive tool which can lead to the development of clinically relevant biomarker for
%U http://www.hindawi.com/journals/isrn.pulmonology/2012/247631/