Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer

Genomic DNA was obtained from the whole blood of 124 breast cancer patients and 97 cancer-free healthy women living in Taiwan. MDM2 SNP309 genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. The multivariate logistic regression and the Kaplan-Meier method were used for analyzing the risk association and significance of age at diagnosis among different MDM2 SNP309 genotypes, respectively.Compared to the TT genotype, an increased risk association with breast cancer was apparent for the GG genotype (OR = 3.05, 95% CI = 1.04 to 8.95), and for the TG genotype (OR = 2.12, 95% CI = 0.90 to 5.00) after adjusting for age, cardiovascular disease/diabetes, oral contraceptive usage, and body mass index, which exhibits significant difference between cases and controls. Furthermore, the average ages at diagnosis for breast cancer patients were 53.6, 52 and 47 years for those harboring TT, TG and GG genotypes, respectively. A significant difference in median age of onset for breast cancer between GG and TT+TG genotypes was obtained by the log-rank test (p = 0.0067).Findings based on the current sample size suggest that the MDM2 SNP309 GG genotype may be associated with both the risk of breast cancer and an earlier age of onset in Taiwanese women.A functional single nucleotide polymorphism has been identified at position 309 within the first intron of the promoter region of the human MDM2 gene and hence designated SNP 309 [1]. Conversion of the T allele to the G allele in the region causes a higher affinity for the Sp1 transcription activator and subsequently enhances the transcription of MDM2 gene. Over-expression of MDM2 oncoprotein may result in a higher risk of carcinogenesis and accelerated tumorigenesis by negatively regulating p53 tumor suppressor protein [2].Supporting evidence for the hypothesis that MDM2 SNP309 influences tumor formation is derived from the clinical outcomes obtained from different research groups. The median age of cancer