Jacobs Eric J, Feigelson Heather Spencer, Bain Elizabeth B, Brady Kerri A, Rodriguez Carmen, Stevens Victoria L, Patel Alpa V, Thun Michael J, Calle Eugenia E
Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, USA.
Breast Cancer Res. 2006;8(2):R22. doi: 10.1186/bcr1400. Epub 2006 Apr 13.
Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region.
We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls).
We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00-2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02-2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88-1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37-0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer.
Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women.
血管内皮生长因子（VEGF）在促进血管生成中起核心作用，且在乳腺癌中过度表达。VEGF基因中至少有四种多态性与VEGF表达水平的变化相关：-2578C/A、-1154G/A和-634G/C均位于启动子区域；+936C/T位于3'非翻译区。
我们在癌症预防研究II（CPS-II）营养队列中研究了这四种VEGF多态性与绝经后女性患乳腺癌风险之间的关联。该队列于1992年建立，参与者被邀请在1998年至2001年期间提供血样。本分析纳入了501名在1992年至2001年期间提供血样并被诊断为乳腺癌的绝经后女性（病例组）。对照组为年龄、种族及血样采集日期与病例组匹配的504名无癌绝经后女性（对照组）。
我们发现所检测的任何多态性与总体乳腺癌风险之间均无关联。然而，在浸润性癌（n = 380）和原位癌（n = 107）的单独分析中，关联明显不同。均被假定可增加VEGF表达的-2578C和-1154G等位基因与浸润性乳腺癌风险增加相关（-2578 CC与AA相比，比值比[OR]为1.46，95%置信区间[CI]为1.00 - 2.14；-1154 GG与AA相比，OR为1.64，95% CI为1.02 - 2.64），但它们与原位癌风险无关。同样被假定可增加VEGF表达的+936C等位基因与浸润性乳腺癌无明显关联（+936 CC与TT/CT相比，OR为1.21，95% CI为0.88 - 1.67），但与原位癌风险降低相关（CC与TT/CT相比，OR为0.59，95% CI为0.37 - 0.93）。-634 C/G多态性与浸润性癌或原位癌均无关。
我们的研究结果为以下假设提供了有限支持，即-2�78C和-1154G VEGF等位基因与绝经后女性浸润性而非原位乳腺癌风险增加相关。
