Angela Cox, senior lecturer at the Institute of Cancer Studies at the University of Sheffield, U.K., led the study, which included more than 30,000 women and 20 research groups from every corner of the globe, from the United States to Australia, Finland to Singapore.

The group -- called the Breast Cancer Association Consortium -- tested genetic variants, called "single nucleotide polymorphisms," from nine different genes that previously had been implicated in breast cancer through small-scale studies. Most of the studies involved women of European descent, in whom the risk of breast cancer is about o­ne-in-nine.

"This study aimed to confirm or refute those previous reports by doing a big study with good statistical power to determine which of these nine [genes], if any, were really associated with breast cancer," Cox said.

The team found "strong statistical evidence" that o­ne variant, a single amino acid change in the CASP8 gene, was associated with a small reduction in breast cancer risk in European women. Carrying this genetic variant decreased a woman's risk of disease by 10 percent, lowering her risk from o­ne-in-nine to o­ne-in-10, Cox said.

The findings were published Sunday in the journal Nature Genetics.

Another genetic variant in the TGF-beta1 gene, had a "slightly weaker association," Cox said, increasing the risk of disease by 7 percent, and the other seven showed "no or o­nly marginal evidence" of being associated with breast cancer.

"This study demonstrates how genes that confer modest effects o­n breast cancer risk can be identified when sufficiently large data sets are assembled," said U.S. National Cancer Institute Director Dr. John E. Niederhuber, in a written statement. "Analyses of this type should help accelerate our ability to target the right genes for very specific subsets of disease."

According to Cox, these new findings place CASP8 and TGF-beta1 o­n the opposite end of the breast cancer susceptibility spectrum from the two best known genes associated with a rise in breast cancer risk, BRCA1 and BRCA2. Mutations in BRCA1 and BRCA2 are rare, she said, but very powerful. Other variants confer a two-fold effect o­n risk.

The variants identified in this study are much weaker and may influence disease susceptibility as much as lifestyle factors, such as the number of children a woman has and her age at childbirth.

The CASP8 protein participates in programmed cell death, or apoptosis -- a normal cellular mechanism involved in organism development and anti-cancer defenses, said Dr. Montserrat Garcia-Closas, a study coauthor and investigator in the NCI's Division of Cancer Epidemiology and Genetics. "DNA damage can trigger [cancer cell] apoptosis, and o­ne hypothesis is that the CASP8 variant may enhance the body's ability to clear cancerous cells from the body and thereby lower the risk of breast cancer," she said.

Cox emphasized that, because of the small influences, positive or negative, exerted by these genes, this study will not likely lead to the immediate development of new genetic tests. "There isn't any immediate implication for women with breast cancer or a family history of breast cancer," she said. "It will not lead to any diagnostic test, because the gene we identified o­nly has a weak effect o­n anybody's risk of breast cancer."

It is possible, however, that CASP8 and TGF-beta1, when combined with other (as-yet-unidentified) variants, could exert a significant enough effect o­n breast cancer susceptibility to make development of a diagnostic test worthwhile.

"In the near future, we might be able to identify a panel of variants with small increases in risk that collectively may put a woman at a much higher risk," Garcia-Closas said.

"It's very, very interesting," said Dr. Jay Brooks, chief of hematology/oncology at Ochsner Health Systems in Baton Rouge, La. "It's an exciting observation that we may be able to identify women who are at a decreased risk of developing breast cancer."

Brooks believes genetics will teach us much more about breast cancer and other malignancies.

"Hopefully, this will lead to better ways to understand [cancer] in terms of understanding how to prevent it, and how to treat it," he said. "For example, why is it that 90 percent of people that smoke never develop lung cancer? We don't have a foolproof way of predicting which individuals will not develop lung cancer ... but there is a clear genetic susceptibility to developing the disease."

"This is the beginnings of understanding the molecular susceptibility of individuals to various cancers," Brooks added. "There are genes that protect us, and we don't completely understand why that is."