Link made between dietary folate, genetic instability and bladder cancer risk

TORONTO - Individuals who are especially susceptible to genetic damage to their cells and who don't eat enough dietary folate are almost three times as likely to develop bladder cancer as are those who eat plenty of fruit and vegetables and who have efficient capacity to repair DNA damage, say researchers from The University of Texas M. D. Anderson Cancer Center. Their study, published in the Proceedings for the 2003 Annual Meeting of the American Association for Cancer Research, clarifies a connection between lower intake of dietary folate and bladder cancer.

"The findings may have important implications for cancer prevention in susceptible populations," says Matthew Schabath, a predoctoral researcher working in the Department of Epidemiology.

He says that the ability to fix errant changes in DNA is of critical importance to maintain normal genetic structure, and this capability varies within the population. "A good prevention practice would be to limit exposure to DNA damaging agents (of which cigarette smoking is the most relevant for bladder cancer) and to eat foods containing folates and folic acid, such as fruits, vegetables, and fortified cereal grains, or take a daily supplement of folic acid, to reduce their risk of developing bladder cancer," he added.

Folic acid deficiency is one of the most common nutritional deficiencies in developed countries. Prior to the fortification of foods with folate, the deficiency was estimated to affect 10 percent of the U.S. population.

Folate itself is crucial to DNA synthesis and repair, Schabath says, so people who don't eat enough folate and who had inherited genetic instability are at much greater risk, he says.

Low intake of folate has already been associated with a number of cancers, including lung, cervical, colorectal, esophageal, brain, pancreatic and breast cancers, says Schabath.

In this study led by Xifeng Wu, M.D., Ph.D., in the Department of Epidemiology, Schabath and his research colleagues studied 272 patients newly diagnosed with bladder cancer and a control group of 257 healthy volunteers to compare folate intake from the diet and evidence of genetic instability. All of the participants were interviewed using a detailed food questionnaire and results of that survey showed that the control group had a much higher intake of folate than did patients -- a differencewhich was statistically different.

Researchers then drew blood samples to check which variants of four different DNA repair genes study participants had inherited. Three of the genes help eliminate chemicals that become incorporated into DNA because of external damage to a cell, such as by cigarette smoking, and the other gene repairs single errant base pair damage. They also measured the level of genetic instability in a laboratory culture test by "challenging" the blood samples with gamma radiation and with a carcinogenic metabolite associated with cigarette smoke to see if the cells could efficiently repair cell DNA damage.


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