Smoking plus gene variant raises breast cancer risk

NEW YORK (Reuters Health) - Women with a particular gene mutation linked to breast cancer may further raise their risk of the disease if they smoke, a study has found.

The gene in question is known as the ataxia-telangiectasia, or A-T, gene. At least 1 percent of the population carries a mutation in the gene, and women who carry mutated A-T have a higher-than-average risk of developing breast cancer.

But until now it had not been known whether smoking increases this risk even more. Studies on smoking and breast cancer in the population as a whole have generally found little or no evidence that the habit contributes to the disease.

These latest findings, however, should give women yet another reason not to smoke, according to lead researcher Dr. Michael Swift, of the Disease Insight Research Foundation in Ardsley, New York.

While the study focused only on women with an A-T mutation, most women who carry such a mutation do not know it, Swift told Reuters Health.

So it's wise -- for a whole range of health reasons -- for all female smokers to give up the habit.

Most people do not know whether they have an A-T mutation because the defect causes no symptoms when a person carries only one copy of the mutated gene. In the uncommon case where a child inherits two copies of a mutated A-T gene -- one copy from each parent -- it causes ataxia- telangiectasia, a disorder that attacks the nervous system.

So while parents of children with ataxia-telangiectasia know they are carriers, most carriers remain unaware.

For the current study, reported in the journal Cancer Epidemiology, Biomarkers and Prevention, Swift's team used data on 859 women who'd been recruited into a long-term A-T gene study between 1971 and 1999.

All had a family member affected by ataxia-telangiectasia, and blood and tissue tests had confirmed that 539 carried an A-T mutation.

Among the gene carriers who did not smoke, 21 percent developed breast cancer by the age of 80. In contrast, a full 80 percent of carriers who smoked developed the disease.

Of women who did not carry an A-T mutation, 16 percent of non-smokers and 20 percent of smokers developed breast cancer before the age of 80 -- an insignificant difference in statistical terms.

"Women who know they carry an A-T mutation and are still smoking should certainly get off of it," Swift said.

But the same advice, he added, goes for all smokers. As yet, there is no test for A-T mutations available for the general public.

It's not clear why the combination of smoking and a mutated A-T gene carries such a high long-term risk of breast cancer. Smoking damages the DNA within body cells, and the A-T gene is involved in repairing such damage; so it's possible that people with an A-T mutation are unable to overcome the gene-level harm that smoking causes.

SOURCE: Cancer Epidemiology, Biomarkers and Prevention, November 2008.