Study Shows Genetic Connection Between Cigarette Smoking And Breast-Cancer Risk

BUFFALO, N.Y. -- Research at the University at Buffalo has yielded further evidence of a genetic link between cigarette smoking and breast-cancer risk in humans.

A study conducted by UB scientists has shown that female smokers who have the slow-acting genotype for N-acetyltransferase(NAT2), an enzyme known to detoxify carcinogenic compounds in cigarette smoke, could have eight times the risk of developing breast cancer compared with women born with the fast-acting NAT2 gene. The two genotypes are referred to as slow acetylators and fast acetylators.

The study was done in collaboration with the National Cancer Institute.

Results of the research will be presented for the first time on Sunday, March 19, at an 11 a.m. press briefing at the American Association for Cancer Research meeting in Toronto. The study was conducted in collaboration with the National Cancer Institute.

Christine Ambrosone, Ph.D., post doctoral fellow in the UB Department of Social and Preventive Medicine and lead author on the study, cautioned that the findings must be corroborated to substantiate their validity and to determine if they apply to women in general.

However, she pointed out that smoking clearly increased the risk of breast cancer for women with the slow-acetylation genotype in this study.

"It is one more cancer site in which cigarette smoking has been implicated," she stated.

The research provides new insight into why previous epidemiologic studies may have failed to show a consistent association between cigarette smoking and breast cancer, in the face of evidence that tobacco smoke is a cancer risk factor at many other organ sites.

Research by other investigators has shown that smokers with the slow-acetylation genotype for NAT2 had higher levels of tobacco¹s carcinogenic compounds in their bloodstream and were at increased risk of developing bladder cancer.

Hypothesizing that differences in NAT2 genotype also may be relevant to the risk of breast cancer among smokers, the UB researchers analyzed the characteristics of the NAT2 gene in the DNA of 159 postmenopausal women with breast cancer and 203 cancer-free women in a control group.

Extensive information on smoking history, as well as health history in general, was collected through personal interviews.

Their analysis revealed a strong association between smoking and breast cancer for women with the slow-acetylation genotype. The risk was highest for women who began smoking before the age of 18. Intensity of smoking -- the number of cigarettes smoked per day at two, 10 and 20 years prior to the interview -- appeared to be more significant than duration of smoking. Among slow acetylators, there was a five-fold increase in risk for women who smoked more than a pack a day.

There were no significant associations between breast-cancer risk and total years smoked, packs per average year, or pack-years smoked among rapid acetylators.

"These findings on breast cancer require substantial replication, but the potential implications may be important," Ambrosone said. "If further investigations in other study populations reveal similar associations between NAT2 genotype, cigarette smoking and breast-cancer risk, it would be an important insight into the etiology of breast cancer.

"There are many health reasons to stop smoking," Ambrosone added. "These data suggest that decreasing their risk of breast cancer gives women one more reason."

Additional researchers involved in the study were Jo L. Freudenheim, Ph.D.; Saxon Graham, Ph.D.; John E. Vena, Ph.D.; John R. Brasure; Arthur M. Michalek, Ph.D.; Rosemary Laughlin, Ph.D.; James R. Marshall, Ph.D., and Takuma Nemoto, M.D., all from the UB Department of Social and Preventive Medicine.

Also, K. Gillenwater, Anita Harrington and Peter G. Shields, M.D., from the Laboratory of Human Carcinogenesis, National Cancer Institute.