The MDM2 protein, a p53 inhibitor, is involved in cell cycle control and apoptosis. MDM2 may promote tumorigenesis when over expressed, amplified or mutated. The expression of MDM2 has been shown to be modified by some functional single nucleotide polymorphisms (SNPs). SNP309, a T → G transversion, is localized to position 309 in the MDM2 P2 promoter. An association between SNP309 and lung cancer has been reported. However, there is no functional data for this SNP in human lung cells. In this project the MDM2 P2 promoter activity with T/T or G/G SNP309 genotypes in human lung cells was characterized. Two luciferase reporter vectors containing the SNP309/P2 region (SNP309-T/G-Luc) were constructed and transfected into human lung cells. Since MDM2 has been associated with an increased risk of cancer in women and has been reported to interact with estrogen receptors, SNP309 estrogen responsiveness was also investigated. This was done by exposure of the SNP309-T/G-Luc-transfected cells with 17β-estradiol. SNP309-T/G-Luc transcriptional activity was significantly higher with the T/T genotype in lung cell lines. To rule out a tissue specific effect, cell lines derived from breast, colon and cervix were investigated. Consistently, the SNP309-T/T-Luc reporter vector had a higher transcriptional activity. Estrogen exposure in 4 human lung cell lines showed no significant effect on transcriptional activity. Still, the T/T genotype showed a higher transcriptional activity, except in one cell line where there was no difference between the two genotypes. A trend indicating a decreased transcriptional activity for G/G in the female lung cancer cell line NCI-H2009 was observed. For SNP309 further elucidation of interacting factors and possible linkage with other SNPs, need to be investigated. A second functional SNP, C1797G, in the MDM2 P1 promoter was recently identified and shown to affect MDM2 mRNA levels. An association between C1797G and risk for bladder cancer has been observed. The role of this polymorphism in susceptibility to lung cancer has not been investigated. In this project its association with lung cancer in a panel of lung cancer patients and healthy controls from Norway was investigated. The results showed a possible protective effect for lung cancer in C1797G heterozygote subjects after adjustment for age, sex and smoking. This effect was only seen for female smokers and was statistically significant indicating a gender-specific effect. Functional studies of this SNP should be performed to investigate the underlying mechanisms for the observed protective effect.