Study links new genetic anomalies to breast cancer in African-American families

The "Jewels in our Genes" study, led by University at Buffalo researcher Heather Ochs-Balcom, has uncovered previously unknown segments of DNA shared by African American family members who have breast cancer.

"The discovery of these regions supports our hypothesis that there are still undiscovered breast cancer genes that may be unique to African Americans," says Ochs-Balcom, PhD, a genetic epidemiologist in the UB Department of Epidemiology and Environmental Health. "We can now focus on these specific chromosomes to learn if they house genetic mutations linked to breast cancer.

"We also need to determine whether those mutations are found in other racial groups or if they are unique to African Americans. If they are unique, it could explain why young African American women have a higher risk of pre-menopausal breast cancer compared to other groups," she says.

"Our study used linkage analysis, a powerful tool that helps to detect the chromosomal location of disease genes by examining genetic markers across the entire human genome. Our family-based gene hunt is similar to the groundbreaking study among women with European ancestry done in the early 1990s that led to the discovery of BRCA1 and BRCA2 gene mutations, which greatly increase susceptibility to breast and ovarian cancer."

African American women can also carry the BRCA mutations, but Ochs-Balcom suspects there may be additional, undiscovered mutations linked to breast cancer in this population.

"Family studies like this one have been difficult to conduct in the past," Ochs-Balcom says, "in part because it's difficult to get multiple family members to commit the time needed to participate. We found here that approaching the recruitment of African Americans by using a multi-pronged approach that included collaboration from our community partnerships greatly facilitated success."

Breast cancer incidence is lower in African-American than in Caucasian-American women, yet breast cancer mortality rates are paradoxically higher for African-American women. These poorly understood disparities have been consistently documented in population-based data from the Surveillance, Epidemiology, and End Results (SEER) program since its inception in 1976. Another notable feature regarding ethnicity-related variation in the epidemiology of breast cancer is that African-American women face a greater risk for being diagnosed with early-onset disease. This review summarizes the information available on the epidemiology of breast cancer in African-American women, as well the possible socioeconomic, genetic, and primary tumor biologic factors that account for these variations.

The prevalence and strength of the established breast cancer risk factors among African-American women are not well documented, but some differences in the significance of various factors have been reported in analyses of the Contraceptives and Steroid Hormone (CASH) study. Mayberry and Stoddard-Wright analyzed standard familial and gynecologic risk factors among breast cancer cases (3,934 Caucasian Americans, 490 African Americans) and controls (3,901 Caucasian Americans, 485 African Americans) from the CASH study and found that age at first live birth, parity, and surgical menopause had similar associations with breast cancer risk, but family history and age at menarche behaved differently as risk factors. For African Americans, first-degree and second-degree family history of breast cancer had comparable strengths as risk factors (odds ratios, 1.61 and 1.71, respectively), whereas the association in Caucasian Americans was notably stronger in relation to the pattern of family history (odds ratio, 2.16 for first-degree relatives, and 1.44 for second-degree relatives). Relatively younger ages at menarche have also been reported for African-American women, but the impact of this finding on breast cancer incidence has not been defined.