Slow Gene Linked to Breast Cancer

Some women smokers with a common variation of a gene may be predisposed to breast cancer, says a report in the 13 November issue of the Journal of the American Medical Association. The study, the authors say, is the first to look at genetic variability as a factor in a person's susceptibility to breast cancer from carcinogens in tobacco smoke.

The gene in this case codes for N-acetyltransferase 2 (NAT2), an enzyme that helps detoxify aromatic amines, common carcinogens in tobacco smoke and cooked meat. Scientists have known for years that people are born with one of several versions of this gene, and that the enzyme coded by each version varies in its detoxification prowess. Less efficient NAT2 versions, called slow acetylators, are present in 40% to 80% of people, depending on their ethnic background.

A team from the State University of New York, Buffalo, and the National Cancer Institute (NCI) looked at 304 white women with primary breast cancer and 327 controls. (An estimated 57% of white women have a slow-acetylator gene.) They found that postmenopausal women smokers with a slow-acetylator gene had an increased risk of breast cancer. The subset most at risk was slow-acetylating women who smoked more than a pack a day for 20 years--they were seven times as likely as controls to develop breast cancer.

The findings bolster a tenuous link between smoking and breast cancer. They also fit with findings on similar inherited mutations that could prove useful to physicians treating a range of cancers. "Discovery of mutations that predispose to cancer is a useful advance" that could affect medical practice, says geneticist Henry Lin of Harbor-UCLA Medical Center. But genetic counseling for NAT2 could send the wrong message, warns NCI molecular epidemiologist Peter Shields, one of the study's authors. Shields hopes women with rapid acetylators do not take home a message that they should continue smoking. "There's never a justification to smoke," he says.