Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Italy.
Cancer Biomark. 2010;8(2):61-5. doi: 10.3233/DMA-2011-0826.
Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.
表皮生长因子受体（EGFR）家族成员（EGFR、HER2、HER3 和 HER4）在癌症的发生和发展中可能具有重要作用，因此受到了广泛的研究。在结直肠癌（CRC）中，EGFR 家族经常过度表达，因此开发了针对 EGFR 的治疗方法。有趣的是，已经观察到这些受体的遗传变异可能会改变 EGFR 抑制剂的治疗效果。EGFR 家族成员的多态性变体可能会影响不同的生物学活性，例如配体亲和力、二聚化效率、激酶活性、表达水平，从而对信号通路和细胞行为产生影响。本研究旨在验证 EGFR 家族成员的单核苷酸多态性（SNPs）是否可以作为易感性因素，影响结直肠癌的发病风险。使用 70 名意大利结肠癌患者和 72 名健康对照者的外周血作为基因组 DNA 的来源，研究 EGFR、HER2 和 HER3 常见的非同义 SNPs。进行遗传关联测试以验证与 CRC 之间的可能关系。在显性遗传模式下，发现 EGFR R521K 多态性存在基因型关联证据（Mid-P=0.031）。EGFR R521K SNP 变体等位基因的基因型可降低 CRC 的发病风险。
