Hirsch Ariel E, Atencio David P, Rosenstein Barry S
Department of Radiation Oncology, New York University Medical Center, New York, NY, USA.
Breast Cancer Res Treat. 2008 Jan;107(1):139-44. doi: 10.1007/s10549-007-9531-x. Epub 2007 Feb 27.
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.
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).
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.
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.
据报道，共济失调毛细血管扩张症突变（ATM）基因杂合的女性，即ATM携带者，与该基因无变异的女性相比，患乳腺癌的风险更高。除了BRCA1和BRCA2外，关于非裔美国女性乳腺癌易感基因的数据很少。本研究的目的是确定是否有证据表明ATM是非裔美国女性的乳腺癌易感基因。
对132名非裔美国女性进行ATM序列改变筛查。其中37名（28%）为经组织学诊断患有乳腺癌的女性（病例组）。这些女性并非基于乳腺癌家族史入选。95名（72%）为年龄匹配且未被诊断患有乳腺癌的女性（对照组）。使用变性高效液相色谱（DHPLC）鉴定基因变异。
37例病例中有23例（62%）至少携带一种ATM变异。95名年龄匹配的对照组中有58例（61%）（P = 0.54）携带至少一种ATM变异。对于特定携带错义变异的受试者，46%的病例和48%的对照组有此类序列变异。此外，19%的病例和34%的对照组携带多种ATM序列变异（P = 0.07）。最常见的多态性为378 T→A，在19%的病例和27%的对照组中出现（P = 0.22）；5557 G→A在22%的病例和18%的对照组中被鉴定到（P = 0.40）；2685 A→G在11%的病例和6%的对照组中被检测到（P = 0.22）；1254 A→G在3%的病例和9%的对照组中被发现（P = 0.36）。因此，病例组和对照组之间检测到的任何基因变异均无显著差异。
我们发现，与年龄匹配的未患乳腺癌的非裔美国女性队列相比，被诊断患有乳腺癌的非裔美国女性在ATM变异的总体频率、任何特定变异类型或组方面均无统计学显著差异。因此，在一般非裔美国人群中，ATM似乎不代表乳腺癌易感基因。
