DNA methylation, field effects, and colorectal cancer.

Abstract

The concept of field effect was first introduced by Slaughter et al. ( 1 ) in 1953, when they studied the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. This concept, also called field defect or field cancerization, was proposed to explain the development of multiple primary tumors in the same organ and locally recurrent cancer. Field effects are considered to underlie the multicentricity of cancer in many, if not all, patients who have multiple tumors in the same organ but no apparent familial predisposition to those tumors. In the multistep carcinogenesis model proposed by Fearon and Vogelstein ( 2 ) , genetic alterations occur in a stepwise fashion such that a clone that has growth advantage proliferates, acquires more genetic alterations, and undergoes another selection for survival and growth, eventually resulting in cancer. According to this model, precancerous cells that are in proximity to cancer cells should have at least some, but not all, of the genetic alterations that are present in the fully developed cancer. In support of this model are observations of genetic alterations in fields of precancerous cells in a variety of organs, including lung ( 3 ) , esophagus ( 4 ) , vulva ( 5 ) , cervix ( 6 ) , and urinary tract ( 7 ) . Alterations in DNA methylation patterns may also potentially contribute to field effects ( 8 ) . Aberrant DNA methylation has been demonstrated in a variety of tissues, including in esophageal mucosa in Barrett's esophagus ( 8 ) , in colonic mucosa affected by ulcerative colitis ( 9 ) , in normal-appearing bladder mucosa ( 10 ) , in normal-appearing gastric mucosa ( 11 ) , and in normal-appearing bronchus in lung cancer resection specimens ( 12 ) .