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

2014; Impact Journals LLC; Volume: 5; Issue: 18 Linguagem: Inglês

10.18632/oncotarget.1910

1949-2553

Stian Knappskog, Liv B. Gansmo, Khadizha Dibirova, Andres Metspalu, Cezary Cybulski, Paolo Peterlongo, Lauri A. Aaltonen, Lars J. Vatten, Pål Romundstad, Kristian Hveem, Peter Devilee, D. Gareth Evans, Dongxin Lin, Guy Van Camp, Vangelis G. Manolopoulos, Ana Osório, Lili Milani, Tayfun Özçelık, Pierre Zalloua, Francis Mouzaya, E. A. Bliznetz, Elena Balanovska, Elvira Pocheshkova, Vaidutis Kučinskas, Л. А. Атраментова, Pagbajabyn Nymadawa, К. С. Титов, Maria Lavryashina, Yuldash Yusupov, Natalia Bogdanova, Sergey Koshel, Jorge Zamora, David C. Wedge, Deborah Charlesworth, Thilo Dörk, Oleg Balanovsky, Per Eystein Lønning,

Genomics and Chromatin Dynamics

// Stian Knappskog 1,2 , Liv B. Gansmo 1,2 , Khadizha Dibirova 3 , Andres Metspalu 4 , Cezary Cybulski 5 , Paolo Peterlongo 6,7 , Lauri Aaltonen 8 , Lars Vatten 9 , Pål Romundstad 9 , Kristian Hveem 9 , Peter Devilee 10,11 , Gareth D. Evans 12 , Dongxin Lin 13 , Guy Van Camp 14 , Vangelis G. Manolopoulos 15 , Ana Osorio 16 , Lili Milani 4 , Tayfun Ozcelik 17 , Pierre Zalloua 18 , Francis Mouzaya 18 , Elena Bliznetz 3 , Elena Balanovska 3 , Elvira Pocheshkova 19 ,Vaidutis Kučinskas 20 , Lubov Atramentova 21 , Pagbajabyn Nymadawa 22 , Konstantin Titov 23 , Maria Lavryashina 24 , Yuldash Yusupov 25 , Natalia Bogdanova 26,27 , Sergey Koshel 28 , Jorge Zamora 29 , David C. Wedge 29 , Deborah Charlesworth 30 , Thilo Dörk 31 , Oleg Balanovsky 3,32 and Per E. Lønning 1,2 1 Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway 2 Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway 3 Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia 4 Estonian Genome Center, University of Tartu, Tartu, Estonia 5 Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland 6 IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy 7 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 8 Department of Medical Genetics, University of Helsinki, Helsinki 00014, Finland 9 Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7489, Norway 10 Department of Human Genetics, Leiden University Medical Center, RC Leiden 2300, The Netherlands 11 Department of Pathology, Leiden University Medical Center, RC Leiden 2300, The Netherlands 12 Genetic Medicine, MAHSC, University of Manchester, St. Mary’s Hospital, Manchester, M13 OJH, UK 13 Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 14 Department of Medical Genetics, University of Antwerp, Antwerp, Belgium 15 Laboratory of Pharmacology, Democritus University of Thrace Medical School, Alexandroupolis, Greece 16 Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, CNIO, Madrid, Spain 17 Bilkent University, Faculty of Science, Department of Molecular Biology and Genetics, Ankara, Turkey 18 Lebanese American University, Chouran, Beirut, Lebanon 19 Kuban Medical University, Krasnodar, Russia 20 Department of Human and Medical Genetics, Vilnius University, Faculty of Medicine, Vilnius, Lithuania 21 Department of Genetics and Cytology, Karazin Kharkiv National University, Kharkiv, Ukraine 22 Mongolian Academy of Medical Sciences, Ulaanbaatar, Mongolia 23 N.N. Blokhin Russian Cancer Research Center RAMS, Russia 24 Kemerovo State University, Kemerovo, Russia 25 Institute for Humanities Research of the Republic of Bashkortostan 26 N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus 27 Department of Radiation Oncology, Hannover Medical School, Hannover, Germany 28 Department of Cartography, Lomonosov Moscow State University, Moscow, Russia 29 Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK 30 University of Edinburgh, Institute of Evolutionary Biology, Edinburgh, Midlothian, Scotland 31 Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany 32 Vavilov Institute of General Genetics RAS, Moscow, Russia Correspondence: Per Lønning, email: // Keywords : MDM2, SNP285, SNP309, polymorphism, promoter Received : February 17, 2014 Accepted : April 16, 2014 Published : April 18, 2014 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.