Smoking Is Related To Subset Of Colorectal Cancers

Main Category: Smoking / Quit Smoking
Also Included In: Colorectal Cancer
Article Date: 15 Apr 2008 - 4:00 PDT

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According to research from a team of Mayo Clinic scientists, smoking puts older women at significant risk for loss of DNA repair proteins that are critical for defending against development of some colorectal cancers.

In a study being presented at the annual meeting of the American Association for Cancer Research (AACR), the researchers found that women who smoked were at increased risk of developing colorectal tumors that lacked some or all of four proteins, known as DNA mismatch repair (MMR) proteins. These proteins keep cells lining the colon and rectum healthy because they recognize and repair genetic damage as well as mistakes that occur during cell division.

Researchers believe that, in this study population, few if any of the four proteins were absent because of an inherited genetic alteration. "We think that smoking induces a condition within intestinal cells that does not allow MMR genes to express their associated proteins, and this loss leads to formation of tumors in some women."

Mayo gastroenterologist, Paul Limburg, M.D. said, "Our findings suggest that tumors may form because cells can't repair themselves from damage induced by smoking. Tobacco toxins appear to block the DNA repair genes from producing their beneficial proteins."

"We are beginning to realise that there might be different risk factors for different subsets of colon and rectal cancers. Smoking is emerging as a potentially important, modifiable risk factor among postmenopausal women," he says.

He added, "The findings also could have other clinical implications with respect to chemotherapy, as tumors that lack MMR proteins might respond differently to standard treatment regimens."

The research team examined data from the 41,836-participant Iowa Women's Health Study and selected those 1,421 women who developed colorectal cancer since the study began in 1986. They then worked with the Iowa Cancer Registry and pathology laboratories around the state to collect tumor specimens from these patients.

When the scientists examined colorectal cancers in female smokers with the perspective of MMR-deficient gene involvement, there was a strong association between smoking and MMR-negative status. For example, former smokers had a 61 percent increase in relative risk for MMR-negative colorectal cancer compared to never smokers, and current smokers were more than twice as likely to develop colorectal tumors with absent mismatch repair proteins.

Dr Limberg saus, "The association between smoking and MMR-negative colorectal cancer also steadily increased with the number of cigarettes a woman smoked per day. The relative risk for MMR-negative cancer increased 54 percent if a patient smoked 1--19 cigarettes daily, more than twofold for 20 cigarettes a day, and more than threefold for a woman who smoked more than 30 cigarettes daily."

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