SLIDE 20 NOTES: Similarly, the cancers that can be seen with colonoscopy alone may be different in terms of progression from those that can be seen with both colonoscopy and virtual colonoscopy. Perhaps tumors located “behind a fold” (and therefore more difficult for virtual colonoscopy) may have a different biologic behavior. We simply do not know whether such is the case at present (Shibata et al., 1996; Carethers et al., 1998; Liefers et al., 1998; Watanabe et al., 2001; Marcella and Miller, 2001; Makinen et al., 2001; Liang et al., 2002; Garcia et al., 2003; McArdle et al., 2003; Rabeneck et al., 2003; Jemal et al., 2003; Kama et al., 2003).

We do know that most advanced adenomas will never develop into clinically apparent cancer. Those that do will take a long time. Some cancers will arise de novo, but we cannot know at present whether they are inherently unique biologically or whether they grew from adenomas that were missed on colonoscopy. This distinction may not matter unless there is one day a major advance in colonoscopic technology.

Increasing age does predict proximal disease, which probably leads to more cancers developing in the interval between screens. In the National Polyp Study, all individuals with interval cancers were over 60. There may be a molecular correlation with this phenomenon: DNA methylation is one cancer pathway that seems to accumulate as people age.

Finally, villous histology is such a strong predictor of cancer risk that there may be a molecular marker that correlates with it. However, to my knowledge no such marker has yet been identified.