Cigarette smoking magnifies breast cancer risk for women with family history of the disease

Smoking cigarettes significantly increases the risk of breast cancer for women with three or more relatives who have had breast or ovarian cancer, according to a new Mayo Clinic study published in the current edition of the journal Cancer Epidemiology, Biomarkers and Prevention (http://cebp.aacrjournals.org/).

"This study suggests to us that smoking contributes to breast cancer in this population," says Fergus Couch, Ph.D., Mayo Clinic molecular geneticist and lead author of the study. "This adds to the evidence that smoking is bad for you. Women with significant family history of breast and ovarian cancer might want to consider avoiding smoking."

The study found that sisters and daughters of the participants who smoked were 2.4 times more likely to develop breast cancer compared to those who had never smoked. The risk was considerably higher yet, a 5.8-fold increased risk, for the 35 very high-risk families in which five or more cases of breast or ovarian cancer had occurred.

"This would make cigarette smoking one of the more significant risk factors for breast cancer in high risk families," says Dr. Couch. "The most significant risk factor is a family history of the disease."

The study findings are in apparent contrast to a 1998 study published in Journal of the National Cancer Institute (http://www.jnci.oupjournals.org/), Volume 90, by Stephen Narod, M.D., and colleagues from the University of Toronto, Ontario, Canada. The Toronto study found that for women who were carriers of the BRCA1 and 2 gene mutations that predispose to breast cancer, cigarette smoking lowered the risk of developing the disease.

"Women with a high risk of breast cancer should not expect smoking to lower their risk," says Thomas Sellers, Ph.D., Mayo Clinic cancer epidemiologist and senior author of the new Mayo study.

The Mayo Clinic study includes a broader spectrum of women at high risk for breast cancer than the University of Toronto study, as it considers all women with three or more relatives with breast or ovarian cancer, not just BRCA1 and 2 gene mutation carriers. The authors consider this an advantage of the new study.

"In over 426 families in our study, 132 families developed three or more breast or ovarian cancers," says Dr. Couch. "By seeing that many of these cancers, it makes us think that these families are at high risk. We are testing them now for gene mutations. They might be BRCA1 or BRCA2 mutation carriers or carriers of a yet undiscovered gene mutation. If you look at a group of people with three or more affected relatives, only about 50 percent have BRCA 1 or 2. The rest may have other unknown genes playing a role."

Cigarette smoking�s cancer-inciting properties are likely the culprit in causing more breast cancers in this high-risk population, according to the Mayo Clinic investigators. "Our feeling is that there are more carcinogens in the blood stream due to smoking," says Dr. Couch. "These carcinogens cause mutations in the DNA of breast cells. Over time, the accumulation of these mutations can lead to the development of cancer in a normal cell."

Though the Mayo Clinic study authors feel confident about the results of their research, they also emphasize that more investigation needs to be conducted on the connection between cigarette smoking and breast cancer for women with a hereditary risk.

"We need other investigators to replicate our finding that smoking further increases familial risk of breast cancer," says Dr. Sellers. "Regardless, there is ample evidence from literally hundreds of studies that document the adverse health effects of smoking."

The current study dates back to 1950, when V. Elving Anderson, Ph.D., professor emeritus of genetics at the University of Minnesota, collected information on family history of cancer for 426 breast cancer patients seen at the University of Minnesota Hospital and Clinics between 1944 and 1952. This information was placed in a basement at the university until 1991, when Dr. Sellers retrieved it, tracked the participants and invited their descendants to participate in a subsequent study. This new portion of the study updated the births and deaths in the family trees of the 426 original participants and added people who had married into the family. Information also was collected on exercise habits, pregnancy history, body measurements and cancer occurrence. The study today has grown to include approximately 12,000 people and spans up to five generations. The current report is based on the approximately 6,600 women who were interviewed regarding cancer occurrence and cigarette smoking history. Further information on this study is available at http://www.mayo.edu:80/research/family_studies/index.html.

Note for reporters: As the women in the Family Studies of Cancer, the cohort in which the present analysis was conducted 1) have no direct patient relationship with the investigators and 2) participated in this study under strict confidentiality agreements, the participants are not available for news media interviews. The lead investigator, Dr. Couch, is available to speak to news media.

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