Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

Stian Knappskog, Liv B. Gansmo, Khadizha Dibirova, Andres Metspalu, Cezary Cybulski, Paolo Peterlongo, Lauri Aaltonen, Lars Vatten, Pål Romundstad, Kristian Hveem, Peter Devilee, Gareth D. Evans, Dongxin Lin, Guy V. Van Camp, Vangelis G. Manolopoulos, Ana Osorio, Lili Milani, Tayfun Ozcelik, Pierre Zalloua, Francis MouzayaElena Bliznetz, Elena Balanovska, Elvira Pocheshkova, Vaidutis Kucinskas, Lubov Atramentova, Pagbajabyn Nymadawa, Konstantin Titov, Maria Lavryashina, Yuldash Yusupov, Natalia Bogdanova, Sergey Koshel, Jorge Zamora, David C. Wedge, Deborah Charlesworth, Thilo Dörk, Oleg Balanovsky, Per E. Lønning

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageBritish English
Pages (from-to)8223-8234
Number of pages12
Issue number18
StatePublished - 2014


  • MDM2
  • Polymorphism
  • Promoter
  • SNP285
  • SNP309


Dive into the research topics of 'Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)'. Together they form a unique fingerprint.

Cite this