Format

Send to

Choose Destination
Oncotarget. 2014 Sep 30;5(18):8223-34.

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

Author information

1
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
2
Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia.
3
Estonian Genome Center, University of Tartu, Tartu, Estonia.
4
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
5
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
6
Department of Medical Genetics, University of Helsinki, Helsinki 00014, Finland.
7
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7489, Norway.
8
Department of Human Genetics, Leiden University Medical Center, RC Leiden 2300, The Netherlands. Department of Pathology, Leiden University Medical Center, RC Leiden 2300, The Netherlands.
9
Genetic Medicine, MAHSC, University of Manchester, St. Mary's Hospital, Manchester, M13 OJH, UK.
10
Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
11
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
12
Laboratory of Pharmacology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
13
Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
14
Bilkent University, Faculty of Science, Department of Molecular Biology and Genetics, Ankara, Turkey.
15
Lebanese American University, Chouran, Beirut, Lebanon.
16
Kuban Medical University, Krasnodar, Russia.
17
Department of Human and Medical Genetics, Vilnius University, Faculty of Medicine, Vilnius, Lithuania.
18
Department of Genetics and Cytology, Karazin Kharkiv National University, Kharkiv, Ukraine.
19
Mongolian Academy of Medical Sciences, Ulaanbaatar, Mongolia.
20
N.N. Blokhin Russian Cancer Research Center RAMS, Russia.
21
Kemerovo State University, Kemerovo, Russia.
22
Institute for Humanities Research of the Republic of Bashkortostan.
23
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
24
Department of Cartography, Lomonosov Moscow State University, Moscow, Russia.
25
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
26
University of Edinburgh, Institute of Evolutionary Biology, Edinburgh, Midlothian, Scotland.
27
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
28
Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia. Vavilov Institute of General Genetics RAS, Moscow, Russia.

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.

PMID:
25327560
PMCID:
PMC4226679
DOI:
10.18632/oncotarget.1910
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center