These observations in conjunction with the observations that both pre-pubescent and post-pubescent females have higher levels of estrogen [33], [34], and that estrogen has been shown to preferentially stimulate the transcription of MDM2 from the G-allele [20], provide a reasonable hypothesis; the G-allele of the MDM2 SNP309 locus could contribute to the increased cancer risk observed in female p53 mutation carriers through the preferential estrogen-dependent stimulation of transcription of the MDM2 gene. The gene discussed is TP53; the disease is cancer.