Lu Hua, Shu Xiao-Ou, Cui Yong, Kataoka Nobuhiko, Wen Wanqing, Cai Qiuyin, Ruan Zhi-Xian, Gao Yu-Tang, Zheng Wei
Department of Medicine, Center for Health Services Research, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8300, USA.
Cancer Res. 2005 Jun 15;65(12):5015-9. doi: 10.1158/0008-5472.CAN-04-2786.
The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. VEGF overexpression has been associated with advanced stage and poor survival of several cancers. We evaluated the association of functional polymorphisms in the VEGF gene with breast cancer survival in a cohort of 1,193 breast cancer patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and followed for cancer recurrence and mortality between March 2000 and December 2002. Included in the study were three functional polymorphisms (C-460T, G+405C, and C+936T) in the VEGF gene. Carrying the -460C or +405G allele was associated with decreased overall survival. The age-adjusted hazard ratios (HR) were 1.5 [95% confidence interval (95% CI), 0.9-2.5] for -460CC genotype carriers and 1.6 (95% CI, 1.0-2.5) for +405GG genotype carriers compared with noncarriers. Further analyses showed that the -460T/+450C/+936C haplotype was related to increased survival (HR, 0.57; 95% CI, 0.4-0.9), whereas the -460C/+405G/+936T haplotype was associated with nonsignificantly decreased survival (HR, 2.1; 95% CI, -0.9 to 4.7). The C+936T polymorphism alone was not related to overall or disease-free survival. This study suggests that VEGF polymorphisms may be a significant genetic marker for breast cancer prognosis.
血管内皮生长因子（VEGF）是血管生成和血管通透性的重要调节因子。VEGF过表达与多种癌症的晚期阶段及不良生存相关。我们评估了VEGF基因功能多态性与乳腺癌生存的关联，研究对象为1193例乳腺癌患者，这些患者于1996年至1998年在中国上海一项基于人群的病例对照研究中被招募，并于2000年3月至2002年12月期间随访癌症复发和死亡率。该研究纳入了VEGF基因的三个功能多态性（C-460T、G+405C和C+936T）。携带-460C或+405G等位基因与总生存期降低相关。与非携带者相比，-460CC基因型携带者的年龄调整风险比（HR）为1.5[95%置信区间（95%CI），0.9 - 2.5]，+405GG基因型携带者的HR为1.6（95%CI，1.0 - 2.5）。进一步分析表明，-460T/+450C/+936C单倍型与生存期增加相关（HR，0.57；95%CI，0.4 - 0.9），而-460C/+405G/+936T单倍型与生存期非显著降低相关（HR，2.1；95%CI，-0.9至4.7）。单独的C+936T多态性与总生存期或无病生存期无关。这项研究表明，VEGF多态性可能是乳腺癌预后的重要遗传标志物。
