title: Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649).
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.
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Liv B
authors.initials: LB
authors.lastname: Gansmo
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia.
authors.forename: Khadizha
authors.initials: K
authors.lastname: Dibirova
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Peterlongo
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Aaltonen
authors.affiliation: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7489, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Vatten
authors.affiliation: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7489, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Romundstad
authors.affiliation: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7489, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.affiliation: Genetic Medicine, MAHSC, University of Manchester, St. Mary's Hospital, Manchester, M13 OJH, UK.
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Evans
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: Laboratory of Pharmacology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
authors.affiliation: Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Lili
authors.initials: L
authors.lastname: Milani
authors.affiliation: Bilkent University, Faculty of Science, Department of Molecular Biology and Genetics, Ankara, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Ozcelik
authors.affiliation: Lebanese American University, Chouran, Beirut, Lebanon.
authors.forename: Pierre
authors.initials: P
authors.lastname: Zalloua
authors.affiliation: Lebanese American University, Chouran, Beirut, Lebanon.
authors.forename: Francis
authors.initials: F
authors.lastname: Mouzaya
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Bliznetz
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Balanovska
authors.affiliation: Kuban Medical University, Krasnodar, Russia.
authors.forename: Elvira
authors.initials: E
authors.lastname: Pocheshkova
authors.affiliation: Department of Human and Medical Genetics, Vilnius University, Faculty of Medicine, Vilnius, Lithuania.
authors.forename: Vaidutis
authors.initials: V
authors.lastname: Kučinskas
authors.affiliation: Department of Genetics and Cytology, Karazin Kharkiv National University, Kharkiv, Ukraine.
authors.forename: Lubov
authors.initials: L
authors.lastname: Atramentova
authors.affiliation: Mongolian Academy of Medical Sciences, Ulaanbaatar, Mongolia.
authors.forename: Pagbajabyn
authors.initials: P
authors.lastname: Nymadawa
authors.affiliation: N.N. Blokhin Russian Cancer Research Center RAMS, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Titov
authors.affiliation: Kemerovo State University, Kemerovo, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Lavryashina
authors.affiliation: Institute for Humanities Research of the Republic of Bashkortostan.
authors.forename: Yuldash
authors.initials: Y
authors.lastname: Yusupov
authors.affiliation: N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.affiliation: Department of Cartography, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Koshel
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Jorge
authors.initials: J
authors.lastname: Zamora
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.affiliation: University of Edinburgh, Institute of Evolutionary Biology, Edinburgh, Midlothian, Scotland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Charlesworth
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia. Vavilov Institute of General Genetics RAS, Moscow, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Balanovsky
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D001208:Asia / Q000453:epidemiology; D057225:Data Mining; D030541:Databases, Genetic; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D065840:Protective Factors; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2