Tiny differences in genes linked to the hormone estrogen can strongly influence a woman’s risk of developing breast cancer, U.S. researchers reported on Wednesday.

They found two variations of a gene called ESR1 that predisposed a woman to breast cancer. One, rare in black women, was associated with the disease only in women over age 50. Another was linked with breast cancer in Ashkenazi Jewish women - those of European descent - over age 50.

Writing in the journal Cancer Research, the researchers said their findings add to a growing list of genes, including BRCA1, BRCA2 and p53, that have mutations associated with breast cancer.

They also found three genetic variations in the ESR1 gene that protected against breast cancer in all ethnic and age groups.

“We were pleasantly surprised to discover that some women have some genetic protection from breast cancer,” said Bert Gold of the National Cancer Institute, who led the study.

All the differences are known as single nucleotide polymorphisms, or SNPs, which are one-letter changes in the genetic code.

Working with the Memorial Sloan-Kettering Cancer Center, Celera Diagnostics SAIC-Frederick Inc., Applied Biosystems, the Massachusetts Institute of Technology and Vanderbilt University School of Medicine, the researchers looked at DNA samples from 1,006 women with breast cancer and 613 without.

In addition to the ESR1 variants, they also found differences associated with cancer in a related gene called ESR2.

“We know that half of familial breast cancer is due to genetic factors other than BRCA1 and BRCA2,” said Dr. Kenneth Offit, a cancer geneticist at Memorial Sloan-Kettering in New York who worked on the study.

“These findings suggest that genetic variants in estrogen receptor pathways may be one of many such risk factors.”

The findings could lead to new treatments for breast cancer, which affects 1.2 million women and some men globally and kills 40,000 a year in the United States alone.

“We hope pharmaceutical developers will take our results into account as they develop new drugs that modulate the effects of estrogen on breast cancer cells,” said the National Cancer Institute’s Dr. Michael Dean.