Abstract
The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 - 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk.
Highlights
The protein encoded by the MDM2 (Mouse Double Minute 2 homolog) gene plays a key role in cell cycle control as a regulator of p53 activity
The importance of MDM2 function is illustrated by the fact that Mdm2 knock-out leads to early embryonic death in mice, which can be reversed by concomitant knockout of the TP53 gene [3, 4]
The findings indicate that the SNP309G allele is associated with an increased risk of several cancer forms in Asian populations while the results in Caucasians are at variance [10, 11], and a study of >5,000 Western European breast cancer patients [12] yielded no associations with cancer risk
Summary
The protein encoded by the MDM2 (Mouse Double Minute 2 homolog) gene plays a key role in cell cycle control as a regulator of p53 activity (the protein coded for by the TP53 gene). We reported the SNP285C variant to be present in about 7.8 % of North-Western Caucasians (Norway, the Netherlands and UK) but to occur at a low incidence among Finns (1.7%), and to be absent in a cohort of Han Chinese [13].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
