Familial colorectal cancer may reflect the influence of multiple genetic factors along with environmental cofactors. Fuchs et al (2002) found that women with high folate intake who had a first-degree relative with colo-rectal cancer were not at increased risk for colorectal cancer. However, women with low folate intake who had a relative with colorectal cancer had about a 2.5-fold increased relative risk for colorectal cancer compared with women with low folate intake and no family history of colorectal cancer. The effect of environmental exposures on risk for cancer among individuals with inherited susceptibility has not yet been studied. However, exposures, such as low folate intake, that are thought to impair DNA repair capacity would be expected to further increase the risk for colorectal cancer among individuals with mismatch repair defects.
Several studies have elucidated relationships between certain environmental exposures and genetic markers in colorectal carcinogenesis. For example, p53 mutations can provide clues to the nature of exogenous agents and endogenous cellular events that are important to the natural history of human cancer. A recent study from Singapore showed K-ras mutations in 28% of 50 specimens from the period 1988-1992 versus 0% in 18 archival specimens from the period 1968-1972 (Tang et al, 1999). The study's researchers concluded that the increase seen over the 30-year period may have been due to the consumption of a western diet, along with increased intake of cooked meat and heterocyclic amines such as 2-amino-3-methylimidazo[4,5-f]quinoline and a resulting increase in aberrant crypt foci, as suggested by tests in experimental animals (Snyderwine et al, 2002).
The rate of mutation in tumors originating in the ascending colon is significantly higher than that in tumors originating in the descending colon, consistent with a decreasing gradient of a mutagen along the length of human colorectum. As such, K-ras activation is potentially a "fingerprint" marker of an as yet unknown exogenous mutagen.
Was this article helpful?
Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.