Rutter Joni L, Chatterjee Nilanjan, Wacholder Sholom, Struewing Jeffrey
Laboratory of Population Genetics, Center for Cancer Research, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Epidemiology. 2003 Nov;14(6):694-700. doi: 10.1097/01.ede.0000083227.74669.7b.
BACKGROUND Over-expression of the human epidermal growth factor receptor 2 (Her2) protooncogene is associated with poor prognosis among female patients with breast cancer. A polymorphism in the HER2 gene (I655V) has been associated with an elevated risk of breast cancer in some ethnic groups. METHODS Subjects from a community-based study of 5318 Ashkenazim from the Washington, DC area were selected for analysis of the I655V HER2 germline polymorphism. We estimated age-specific breast cancer risk from HER2 I655V based on the family history data, using the female first-degree relatives of the study participants and a novel extension of the kin cohort method. RESULTS The estimated cumulative risk of breast cancer to age 70 was approximately 30% higher among HER2 I655V carriers than noncarriers (RR = 1.33; 95% confidence interval [CI] = 1.03-1.83). The effect of the allele seems stronger at younger ages (among women younger than 50 years, RR = 2.11; CI = 1.39-3.28) and especially among younger women with a family history of breast cancer (RR = 8.9; CI = 1.9-19.7). Increased risk of breast cancer associated with the I655V allele was also observed among BRCA1/2 mutation carriers, although these results are based on small numbers. CONCLUSION These analyses suggest that the HER2 valine allele might be associated with increased risk of breast cancer, especially in young women and in women with a family history of the disease.
人表皮生长因子受体2（Her2）原癌基因的过表达与女性乳腺癌患者的不良预后相关。HER2基因（I655V）的一种多态性在一些种族群体中与乳腺癌风险升高有关。方法：从华盛顿特区地区5318名阿什肯纳兹人的社区研究中选取受试者，分析I655V HER2种系多态性。我们使用研究参与者的女性一级亲属以及亲属队列方法的一种新扩展，根据家族史数据估计基于HER2 I655V的特定年龄乳腺癌风险。结果：HER2 I655V携带者到70岁时乳腺癌的估计累积风险比非携带者高约30%（风险比[RR]=1.33；95%置信区间[CI]=1.03 - 1.83）。该等位基因的影响在年轻时似乎更强（50岁以下女性中，RR = 2.11；CI = 1.39 - 3.28），尤其是在有乳腺癌家族史的年轻女性中（RR = 8.9；CI = 1.9 - 19.7）。在BRCA1/2突变携带者中也观察到与I655V等位基因相关的乳腺癌风险增加，尽管这些结果基于少量样本。结论：这些分析表明，HER2缬氨酸等位基因可能与乳腺癌风险增加有关，尤其是在年轻女性和有该病家族史的女性中。
