The concept of field cancerization (also known as field effect or field defect) was introduced in 1953 by Slaughter et al. to explain the develop ment of multiple primary tumors, local recur rence, abnormal tissue surrounding the cancer and multifocal areas of precancerous change [1]. Field cancerization reflected the susceptibility of normal tissue to undergo early genetic changes as a result of exposure to carcinogens, leading to the development of cancer. Even though these initial findings made were based on histo logical obser vations, with the advances in modern molecular techniques, it is now evident that field cancer ization occurs at the molecular level. It has now been established that precancerous cells that are adjacent to the tumor cells harbor tumorspecific genetic alterations in various organs, including the lung [2], esophagus [3], stomach [4], colon [5], prostate [6], breast [7], cervix [8] and so on. More recently, studies have shown that aberrant DNA methylation patterns are potential biomarkers of field cancerization in several cancers. How do environmental factors lead to field cancerization? In a recent study, Lee et al. evalu ated the use of DNA methylation markers for risk assessment of cancer of the upper aero digestive tract (UADT)[9]. The study pop ulation com prised a training set of 255 patients and a valida tion set of 224 patients, in whom lifestyle risk factors, such as alcohol consumption, betel quid chewing and cigarette smoking (abbreviated together as ABC) were recorded along with other demographic characteristics. Interestingly, they observed a stepwise increase in methylation of four genes: healthy subjects without exposure to ABC had the lowest level of methylation in the normal esophageal mucosae, followed by normal mucosae from healthy patients with ABC expo sure, then normal mucosae from cancer patients, and the highest methylation levels were observed in cancerous mucosae. Correlation of increased methylation of a single gene to alcohol consump tion and betel quid chewing was also observed. Smokers had increased methylation of all four markers. All four epigenetic markers were found to be useful as a quantitative measure for field cancer ization along the UADT and methylation of HOXA9 was the best discriminative marker in predicting UADT cancer, although the effect of methylation on geneexpression levels was not determined.

A recent publication by Nanjo et al. identi fied seven novel epigenetic markers for gastric cancer risk [10]. They compared the levels of methyl ation of seven CpG islands (CGI) among healthy volunteers who had never been infected with Helicobacter pylori (group 1), healthy volun teers with current H. pylori infection (group 2), healthy volunteers with past infection (group 3), gastric cancer patients with current infection (group 4) and gastric cancer patients with past infection (group 5). Among the healthy individ uals, methylation levels of the seven CGIs were significantly greater in group 2 than in group 1; however, methylation levels in group 3 were lower than those in group 2, but significantly higher than that of group 1. The authors pro pose that H. pylori infection leads to aberrant methylation in stem cells, and that remains even after infection has been eradicated. Increased methylation of the seven CGIs was observed in group 5 compared with group 3, suggesting that it might be possible to estimate gastric cancer risk in individuals with past H. pylori infection, although prospective studies may be required to prove this hypothesis. It is not clear whether methylation levels/patterns are different in gas tric cancer patients not infected with H. pylori. Hence, it would have been of interest to …