Analysis of the association of Single Nucleotide Polymorphisms in the p53-MDM2 Circuit on the Incidence of Breast Cancer in the Taiwanese Population

• Main Authors: Han-Yi Tsai, 蔡瀚儀
• Other Authors: Yi-Jang Lee
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/16389338964684848891

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系暨研究所 === 98 === The Single nucleotide polymorphisms (SNPs) represent nucleotide variation on human genome, and it may be associated with the risk of cancer regarding the subgroups of selected patients. MDM2 oncoprotein is an important negative regulator of p53 tumor suppressor, and certain SNPs on MDM2 and p53 genes have been reported to be associated with human cancers. In this study, we investigated whether MDM2 SNP309, MDM2 SNP354 and P53 R72P is associated with increased risk and earlier onset of breast cancer in Taiwanese people. Second, we also investigated how MDM2 SNP309 effect on MDM2 promoter in cells. A total of 276 patients with breast cancer and 344 healthy controls were included in this study. We did not observe an association between p53 R72P status and breast cancer incidence. The homozygous type G/G of SNP354 cannot be found, therefore the ORs of SNP354 was unobtainable. A slight risk was observed on MDM2 SNP309 (ORs=1.69, 95% confidence internal [CI]= 0.926 to 3.088). However, the significant association with breast cancer incidence was observed when we detected SNP309 and p53 R72P simultaneously. In our data shows, R/R form on p53 R72P and genotype G/G on MDM2 SNP309 have higher risk than R/R on p53 R72P and T/T on MDM2 SNP309 (ORs= 3.7, 95% confidence internal [CI]= 1.144 to 12.017). As well, Genotype T/T on MDM2 SNP309 and P/P form on p53 R72P have higher risk than T/T on MDM2 SNP309 and R/R on p53 R72P (ORs= 3.22, 95% confidence internal [CI]= 1.001 to 10.36). The luciferase assay data shows, SNP309 T→G leads to higher MDM2 transcription and it may attenuate the p53 response. The Kaplan-Meier survival curve shows, within the patient group with R/R form on p53 R72P, the age of onset of breast cancer is effected by MDM2 SNP309. In conclusion, based on a novel analysis method in this study, combination of MDM2 SNP309 and p53 R72P is more powerful than separated detection to be a breast cancer risk marker in Taiwan.