Older women who smoke are vulnerable to developing colorectal cancer as smoking makes them lose some DNA repair proteins that are essential to fight the cancer, a study by researchers at Mayo Clinic has indicated.
During the study, the researchers found that women who smoked were at increased risk for developing colorectal tumours 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.
According to researchers, in this study population, few if any of the four proteins were absent because of an inherited genetic alteration.
"Our findings suggest that tumours 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," said the study's lead author, Mayo gastroenterologist Paul Limburg, M.D.
He said that the findings also could have other clinical implications with respect to chemotherapy, as tumours that lack MMR proteins might respond differently to standard treatment regimens.
For the study, researchers 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 tumour specimens from these patients.
Till date, they have retrieved about 50 percent of the samples. This study, a first analysis, includes 432 samples, or about 30 percent of the group.
Researchers analyzed the tumours for presence of four DNA mismatch repair proteins known to be active in cells lining the colon and rectum.
Samples that had all four were labelled MMR-positive while tumours with less than four were tagged as MMR-negative.
The researchers then correlated information reported by the patients on whether they had ever smoked and how many cigarettes they used daily with MMR protein patterns in their tumours.
They found that smoking status was not significantly linked to the development of colorectal cancer in the 432 patients in general.
However, when the researchers examined colorectal cancers in women smokers with the perspective of MMR-deficient gene involvement, there was a strong link between smoking and MMR-negative status.
Dr. Limburg said that the link between smoking and MMR-negative colorectal cancer also steadily increased with the number of cigarettes a woman smoked per day.
The study is being presented at the annual meeting of the American Association for Cancer Research (AACR).