Cigarette Smoking and Microsatellite Instability: Causal Pathway or Marker-Defined Subset of Colon Tumors?

Extract

When the average person thinks of cigarette smoking and cancer, the cancers that come to mind are those of the lung and upper aerodigestive tract. Cancer researchers have also long recognized the etiologic association of cigarette smoking with a number of other cancers, such as those of the bladder and pancreas. Until quite recently, however, colon cancer, one of the most common cancers in the United States, was not recognized as being associated with cigarette smoking, this despite the fact that numerous studies (1–3) consistently found an association between cigarette smoking and adenomas, the precursor lesions for most cases of colon cancer.

This seeming paradox, that smoking may be related to colorectal adenomas but not to cancer, has generated much debate. One explanation may be that there is no paradox at all. For example, in two prospective cohort studies, Giovannucci et al. (4,5) reported twofold increases in risk of colon cancer after 35 years of smoking (4,5). Another long-term cohort study has supported these findings (6), although others have not (7–9). At this point, it is safe to say that the association observed between smoking and colorectal cancer has been inconsistent at best.