Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene
Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene
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DOI：
10.1158/0008-5472.can-03-2623
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发表时间：
2004-01-01
期刊：
影响因子：
11.2
通讯作者：
Chang-Claude, J
中科院分区：
文献类型：
--
作者：
Brandt, B;Hermann, S;Chang-Claude, J
表皮生长因子受体（egfr）基因在人类癌症中的调节作用尚未完全清楚。位于egfr基因内含子1的5 '调控序列的多态性CA重复序列[egfr CA简单序列重复序列（SSR）I]的最新数据表明，与egfr基因相关的癌症风险可能遗传。此外，我们已经检测到频繁的等位基因不平衡限制在乳腺癌组织和非肿瘤乳腺组织的EGFR CA SSR I邻近浸润性和原位乳腺癌代表扩增。因此，我们进行了一项基于人群的病例对照研究，以评估egfr基因多态性与乳腺癌风险之间的关系。年龄50岁的首次原发性乳腺癌病例和年龄匹配的人群对照提供了已知和疑似风险因素的信息。egfr CA SSR的等位基因长度在616例和1072人口抽样控制。根据等位基因长度对基因型进行分类分析。多变量逻辑回归用于比较基因型分布，考虑其他危险因素，并调查基因-环境相互作用。我们发现egfr多态性的等位基因长度对乳腺癌风险有修饰作用，尽管没有主要作用。在有乳腺癌一级家族史的女性中，两个长等位基因（大于或等于19 CA）的存在与显著升高的比值比（OR）10.4 [95%置信区间（CI），1.85-58.70]相关（相互作用P = 0.015）。与高红肉摄入相关的风险增加（OR，10.68; 95%CI，1.57-72.58）和高蔬菜摄入的保护作用（OR，0.07; 95%CI，0.004-1.07）在两个长等位基因（大于或等于19 CA）的携带者中也最明显。egfr CA SSR的长度可能会增加家族性乳腺癌的风险，其影响可能受到饮食因素的调节。
The regulation of the epidermal growth factor receptor (egfr) gene in human cancer is not yet fully understood. Recent data on a polymorphic CA repeat located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk associated with the egfr gene. Furthermore, we have detected frequent allelic imbalances restricted to the egfr CA SSR I in breast cancer tissue and nontumorous breast tissue adjacent to invasive and in situ breast cancer representing amplifications. Therefore, we conducted a population-based case-control study to assess the relationship between the egfr polymorphism and breast cancer risk. Cases with a first primary breast cancer by age 50 years and age-matched population controls provided information on known and suspected risk factors. The allelic length of the egfr CA SSR was determined in 616 cases and 1072 population-sampled controls. Genotypes were categorized for analysis by allele length. Multivariate logistic regression was used to compare genotype distributions, accounting for other risk factors, and to investigate gene-environment interactions. We found a modifying effect, albeit no main effect, of the allelic length of the egfr polymorphism on breast cancer risk. The presence of two long alleles (greater than or equal to19 CA) was associated with a significantly elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among women with a first-degree family history of breast cancer (P = 0.015 for interaction). The risk increase associated with high red meat consumption (OR, 10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two long alleles (greater than or equal to19 CA). The length of the egfr CA SSR may increase the risk for familial breast cancers, and its effect could be modulated by dietary factors.