Background: Women who are heterozygous for variants in the ataxia telangiectasia mutated (ATM) gene, ATM carriers, have been reported to be at increased risk for breast cancer compared with women who do not posses an alteration in this gene. Aside from BRCA1 and BRCA2, there are few data on breast cancer susceptibility genes in African-American women. The goal of this study was to determine whether there is evidence that ATM is 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). These women were not selected on the basis of a breast cancer family history. Ninety-five (72%) were age-matched women who had not been diagnosed with breast cancer (controls). Genetic variants were identified using denaturing high performance liquid chromatography (DHPLC).
Results: Twenty-three of the 37 (62%) cases possessed at least one ATM variant. Fifty-eight of the 95 (61%) (P = 0.54) age-matched controls harbored at least one ATM variant. For subjects specifically possessing missense variants, 46% of cases and 48% of controls had these types of sequence variants. In addition, 19% of cases and 34% of controls possessed multiple ATM sequence variants (P = 0.07). The most common polymorphisms were the 378 T --> A which was seen in 19% of cases and 27% of controls (P = 0.22), 5557 G --> A identified in 22% of cases and 18% of controls (p = 0.40), 2685 A --> G which was detected in 11% of cases and 6% of controls (P = 0.22), and 1254 A --> G which was found in 3% of cases and 9% of controls (P = 0.36). Hence, there were no significant differences in any of the genetic variants detected between the case and control subjects.
Conclusion: We found no statistically significant differences in the overall frequency of ATM variants, nor any specific variant type or group, between African-American women who had been diagnosed with breast cancer compared with an age-matched cohort of African-American women who did not have breast cancer. ATM, therefore, does not appear to represent a breast cancer susceptibility gene in the general African-American population.