Screening for ATM sequence alterations in African-American women diagnosed with breast cancer

10037 Background: Women who are heterozygous for mutations in the ATM gene, ATM carriers, are reported to have an increased risk of breast cancer compared with noncarriers of the mutation. There are few data on breast cancer susceptibility mutations in African-American women, particularly the non-BRCA mutations. We set out to determine whether there is evidence that ATM represents a breast cancer susceptibility gene in African-American women. Methods: One hundred thirty-two African-American women were screened for ATM sequence alterations. Thirty-seven (28%) were women with a histological diagnosis of breast cancer (cases) and 95 (72%) were age-matched women who were seen for a screening mammogram and had no evidence of cancer (controls). Genetic variants were identified using Denaturing High-Performance Liquid Chromatography (DHPLC). Results: Eighteen of 37 (49%) cases and 54/95 (57%) possessed at least one ATM variant (p =0.256). Missense variants were seen on 16/37 (43%) cases and 66/95 (69%) controls. In addition, 5/37 cases and 24/95 controls possessed multiple ATM sequence variants (p=0.107). The most common polymorphisms were: 378 T ->A, seen on 7/37 (19%) cases and 26/95 (27%) controls (p=0.219); 2685 A-> G, seen on 5/37 (11%) cases and 7/95 (6%) controls (p=0.217); and 1254 A-> G, seen on 2/37 (3%) cases and 9/95 (9%) controls (p=0.357). There were no significant differences in any of the single nucleotide polymorphisms (SNPs) detected between the cases and controls. Conclusions: We found no significant differences in the overall frequency of ATM variants between African-American women with breast cancer and an age-matched cohort of African-American women without breast cancer. ATM, therefore, does not appear to represent a breast cancer susceptibility gene in the African-American population. Many of the ATM variants that we found in high frequency were consistent with prior reports of common variants in patients of African ancestry. Comparing the difference in the frequency of ATM variants in the African-American population screened in this study with prior reports on non-African-American subjects will enable us to characterize the differential distribution of genetic alterations in various patient populations and lead to more optimally tailored cancer therapy. No significant financial relationships to disclose.