Abstract #3029: Diet and lifestyle factor associations with CpG island methylation in high-risk population
Authors: Leonel Maldonado, Mariana Brait, Jean Ford, Srinivas Papaiahgari, Shahnaz Begum, Myriam Loyo, Mark Emerson, Saifuddin Ahmed, Lee McCaffrey, Mollie Howerton, David Sidransky, Mohammad Hoque
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Cancer is the second leading cause of death in the United States. Several approaches have been evaluated in an effort to predict the risk of developing cancer for two main reasons: prevention and early detection. Many risk factors have been associated with cancer, such as age, family history of cancer, race, smoking, high-fat diet and poor nutrition, among others. It is important to reveal the molecular mechanisms behind the carcinogen exposure and cancer development. Some epigenetic alterations have been shown to be early events in carcinogenesis. CG dinucleotide-rich (CpG islands) gene promoter regions are frequent targets of DNA methylation leading to transcriptional silencing of known or putative tumor suppressor genes. Our study aims to determine the epigenetic changes of cancer related-genes in association of risk factors to which an asymptomatic population has being exposed. We selected six cancer specific methylated genes ( APC , CCND2 , GSTP1 , MGMT , RAR\#946;2 , and P16 ) that have previously been reported in primary tumors and have also been detected in different bodily fluids by our group and others. Here we use quantitative fluorogenic real-time methylation specific PCR (QMSP) in plasma DNA samples from a high risk population who do not have any known cancer. In a cross-sectional study, we tested plasma DNA of 157 African American individuals that were \#8805;40 years. The promoter methylation frequency of the studied genes were: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RAR\#946;2 (29%) and P16 (3%). Methylation of at least one of the genes analyzed was observed in 45.8% (72/157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 16.5% (26/157) of the samples. Statistically significant correlations were observed between the molecular findings and the epidemiologic parameters of the cancer free subjects: RAR\#946;2 methylation was observed in 45% of subjects who had a high fat diet (defined by the consumption of red meat/processed meat and diary or deep fried food at least twice a day), in contrast with those who had a low fat diet (23%) ( p =0.014); 33% of the non-smokers subjects showed CCND2 methylation, what was observed in only 18% of the smokers (P=0.0364). These findings suggest that these epigenetic alterations could be early pre-neoplastic changes and could be useful for cancer prevention measures such as changes in lifestyle, for screening purposes, not only to indentify the individual who may develop cancer, but also to a potential use as therapy targets. Our findings may help elucidate the accumulated epigenetic changes that lead to cancer development due to the exposition to a risk factor. Further longitudinal follow up of a high risk population is needed to understand and confirm the association of promoter hypermethylation of candidate genes and the risk factors and their role in cancer development.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3029.