Journal
ONCOTARGET
Volume 5, Issue 18, Pages 8223-8234Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1910
Keywords
MDM2; SNP285; SNP309; polymorphism; promoter
Categories
Funding
- Bergen Medical Research Foundation
- Norwegian Cancer Society
- LITGEN project [VP1-3.1-SMM-07-K-01-013]
- Cancer Foundation Finland sr [140086] Funding Source: researchfish
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available