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Some Colorectal Cancers Not Connected to Obesity

Although being obese increases risk for most colon and rectal cancers, the connection isn’t true in all types of colorectal cancer.

Cancers that are linked to microsatellite instability (MSI) don’t appear to be influenced by obesity, strengthening the belief that MSI cancers come about differently than the average colorectal cancer.

Overall, in a recent study, body mass index and weight gain during adult life increased risk of colorectal cancer by about 30 percent for men and 20 percent for women. However, increased risk was limited to microsatellite stable or microsatellite low tumors.

Led by Peter T. Campbell, PhD, from the Epidemiology Research Program at American Cancer Society in Atlanta, a research team compared height and weight at age 20 and recent height and weight for nearly 1,800 people with colorectal cancer to figures for 2,700 of their sex-matched brothers and sisters.

They also analyzed tumors for microsatellite instability in 7 out of 10 of the group with cancer.

They discovered a 38 percent increased risk for cancer in patients with microsatellite stable tumors, a 33 percent increased risk in those who had a low number of microsatellite markers, and no increase those whose tumors had high number of microsatellite changes (MSI).

Campbell and his colleagues concluded,

The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

What is microsatellite instability?

Microsatellites are repeated sequences of DNA.  The normal length of microsatellites in an individual’s cells are set at birth, although lengths vary from one person to another.  However, during the many divisions cells undergo in a person’s lifetime, mistakes can be made duplicating DNA which don’t get repaired, so microsatellites change in length in some tissues.  The presence of abnormally short or long microsatellites indicates that genes that should be repairing DNA are mutated and aren’t doing their job.

Mutations in DNA repair genes can lead to a particular form of colorectal cancer linked to microsatellite instability.  About 1 in 6 or 7 (15 percent) colorectal cancers are microsatellite instable. Some people are born with mutations in DNA repair genes, as in Lynch syndrome.  Other acquire mutations during their lives.

SOURCE: Campbell et al., Journal of the National Cancer Institute, Volume 102, Number 6, pages 391-400, March 17, 2010.

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