Family genetics and tobacco linked to higher breast cancer risk

  Tobacco Use, Genetics May Increase Breast Cancer Risk

Smoking may put women with a family history of breast and ovarian cancers at greater risk of developing breast cancer themselves, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, (Vol. 10, No. 4: 327-332).

The multigenerational study contradicts a May 1998 paper published in the Journal of the National Cancer Institute that suggested tobacco might be a protective factor, reducing the risk of breast cancer in women with the mutant BRCA1 or BRCA2 gene, an inherited defect associated with higher risk for breast and ovarian cancers. It is not clear why tobacco may have been considered protective, although some investigators believed it may have been due to decreased estrogen levels in women who were smokers.

"The most important finding was that smoking did not lower the risk of breast cancer in high-risk families," says the new paper’s senior author, Thomas A. Sellers, PhD, an epidemiologist and associate director of the Mayo cancer center. "This is one more reason to avoid smoking."

In this study, researchers from the Mayo Clinic Cancer Center looked at breast and ovarian cancer cases in female relatives of 426 women whose families had a high incidence of those cancers, and who had been diagnosed with breast cancer between 1944 and 1952.

The researchers analyzed a subgroup of 132 families that had at least three cases of breast or ovarian cancers by the end of the follow-up period of 1991 to 1996. Among the sisters and daughters in these higher-risk families, those who smoked were at a 2.4-fold increased risk of breast cancer over those who had never smoked. (Sisters and daughters share 50% of the genes of the original cancer patient.)

In 35 families with the highest genetic risk — that is, there were at least five cases of breast or ovarian cancers in the family history – sisters and daughters who smoked had more than double the risk of developing breast cancer than the nonsmokers. The increased risk among smoking granddaughters and nieces—who share 25% of the original patient’s genes—was 1.7-fold.

Small group of highest-risk patients weakens the conclusion

The data linking cigarette smoking and breast cancer are mixed, with most published studies finding a weak link. Marilyn Leitch, MD, a member of the American Cancer Society breast cancer council and medical director at the University of Texas Southwestern Center for Breast Care, cautions that the number of families in the highest-risk genetic group – 35 – is small, making it difficult to conclude with certainty that smoking definitely increases the risk of developing breast cancer in predisposed women with positive family histories.

"The smokers were more likely to drink alcohol," says Leitch, "which is also shown to be a risk factor for development of breast cancer."

At the Mayo Clinic, Sellers offers two possible reasons for why his study, found an apparent link to the disease. This study is the first to look at multiple generations of families with breast cancer, he says. If smoking is more dangerous for a certain group of susceptible women, previous studies may have missed the thread of that inherited susceptibility, Seller says. Secondly, the age at which women begin smoking has dropped dramatically during 30 years of breast cancer research, he says.

"In 2001, 95% of all smokers begin before age 18," says Sellers. "So if women are exposed during adolescence when breast tissues are growing and dividing rapidly, that may be a more critical period."

He expected to find that if smoking actually increased the risk of breast cancer, as it does in lung cancer, the more women smoked and the longer they smoked, the greater the risk of developing breast cancer. The Mayo group did not see that, however. The team also did not have enough cases to look at the risks of women who never smoked versus former smokers versus current smokers. As a result, the study could not determine whether a woman would decrease her risk of developing breast cancer if she stopped smoking. "It’s an important question," Sellers says, "and additional research is needed to sort that out."

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