The study of the vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2 in women with breast cancer and men with oral cancer patients in Taiwan

• Main Authors: Chia-Chun Chang, 張嘉純
• Other Authors: Li-Yu Tsai
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/59856527696934553787

碩士 === 高雄醫學大學 === 醫學檢驗生物技術學研究所 === 100 === Breast cancer is one of the most common cancers of women in the world. In Taiwan, breast cancer is the 4th leading cause of cancer deaths among women which was nexr to lung cancer, hepatocellular carcinoma and colon cancer. The etiology of breast cancer is multifactorial. Hormonal, genetic and environmental factors appear to interplay in the pathogenesis of breast cancer. Oral cancer is also one of the most common cancers of men in the world. In Taiwan, oral cancer is 6th lethal cacncer of top ten cancers in adult men form 40 to 60 years old. Chewing betle nuts, smoking and genetic mutation might also be one factor that might cause oral cancer. The roles of angiogenesis in tumor metastasis were proposed by Dr. Judah Folkman in 1970s and the progression and metastasis of malignant tumors, including breast cancer, depend on angiogenesis via the supplementation of blood vessels. Vascular endothelial growth factors (VEGFs) which are secreted from tumor cells will bind to its receptors to stimulate the survival, proliferation and migration of epithelial cells and cancer cells. Therefore, they will then enhance the growth and aggravate the progress of tumor. In oreder to clarify whether VEGF (-2578C>A, +405G>C and +936C>A) and VEGFR2 (-604>T>C, +1192G>A and +1719T>A) is associated with breast cancer risk and prognosis, we analyzed those polymorphisms in 283 breast cancer cases and 200 gender-match conrols, and 114 oral cancer cases and 122 gende-match controls form Kaohsiung Medical University Chung-Ho Memorial Hospital by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). And then the date were analyzed the relationship of risk by SPSS 17.0. Besides, we collected 278 breast cancer tissues form 283 breast cancer cases to convince the protein expression of VEGF and VEGFR2 in tumor tissues by immunohistochemistry staining (IHC). Our study of beast cancer indicated that VEGF and VEGFR2 polymorphisms did not have the correlations in overall and postmenopausal breast cancer patients. However, premenopausal women who carried with VEGFR2 +1719G>A A allele had lower risk than those with VEGFR2 +1719G>A G allele (0.6 folds; p-value <0.01). While neither allele alone shows any change in breast cancer risk of breast cancer (0.51, 0.34 and 0.030, respectively) is orserved in individuals who carried VEGFR2 -604T>C/+1192G>A TT-GA, C carrier-GG and Carrier-GA genotypes. In prognosis, there was a significant association between VEGFR2 +1192G>A and tumor sizes (p-value <0.01). Our data showed that there was no association between SNPs of VEGF and VEGFR2 and the protein expression. However, there was a significant positive association and histological stages (p-value =0.02). We also found that patients who were metastasis and triple negative breast cancer (TNB) would had higher VEGFR2 protein expression (p-value =0.03). Our study of oral cancer indicated that individuals with VEGF +405G>C genotype had higher risk than those with GG genotype (1.94 folds, p-value 0.03). Individuals with VEGF +936C>T CT genotype had 1.91 folds risk than those with CC genotype (p-value 0.03). In haplotype analysis, individuals with VEGF -2578/-634/+936 AGC, CCT and CCC g haplotype had 2.5, 4.28 and 2.10 folds risk than those with AGC haplotype (p-value 0.02). Individuals with VEGF +405G>C/+936C>T GG-T carrier, C carrier-CC and C carrier- T carrier genotypes had 2.90, 2.93 and 2.08 folds risk than those with VEGF +405G>C/+936C>T GG-TT genotype; individuals with VEGF+936C>T/-2578C>A T carrier-CC genotype also had 2.64 folds risk than those with CC-CC genotype. In prognosis of oral cancer, our data showed that there was a significant association between patients with VEGFR2 +1192G>A and those with metastasis (p-value=0.01). In conclusion, our data indicates that three points: firstly, the findings support that VEGFR2 polymorphisms and genetic interactions had negative correlations on risk and prognosis of breast cancer. Secondly, VEGF polymorphisms, haplotypes and genetic interaction had positive correlations on risk of oral cancer. Thirdly, there was a significant association between VEGFR2 +1192G>A polymorphism and prognosis in breast and oral cancer. Therefore, we suggests that doctors should consider the consequences of VEGF and VEGFR2 polymorphisms in patients when they treat the breast cancer and oral cancer patients in order to achieve personalized medicine.