MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk.
The del1518 (rs3730485) polymorphism is an in/del variant in the MDM2 promoter P1. The variant is in complete linkage disequilibrium with MDM2 SNP309 (rs2279744) and has previously been found associated with an increased risk of colon cancer. In this study we assessed the impact of MDM2 del1518 on risk of ovarian and endometrial cancer.



Here, we genotyped del1518 in two large hospital-based series of patients diagnosed with ovarian (n = 1,385) or endometrial (n = 1,404) cancer and performed risk estimations as compared to the genotype distribution among 1,872 healthy female controls.



In overall analysis we observed no association between del1518 and risk of either ovarian or endometrial cancer. However, stratifying according to SNP309 status, we found the del1518 variant to be associated with a reduced risk of endometrial cancer among individuals carrying the SNP309TT genotype both in the dominant (OR = 0.64; 95% CI = 0.45 - 0.90) and the recessive model (OR = 0.80; 95% CI = 0.65 - 1.00). No such association was observed for ovarian cancer risk.



We found the MDM2 del1518 del variant to be associated with reduced risk of endometrial cancer among individuals carrying the MDM2 SNP309TT genotype.
Section of Oncology, Department of Clinical Science, University of Bergen, Haukeland University Hospiltal, Jonas Lies veg 87, 5021, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Liv B
LB
Gansmo
Department of Molecular Oncology, Oslo University Hospital Radium Hospitalet, Oslo, Norway.|Institute for Cancer Research, University of Oslo, Oslo, Norway.
Merete
M
Bjørnslett
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway.
Mari Kyllesø
MK
Halle
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway.
Helga B
HB
Salvesen
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Pål
P
Romundstad
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Kristian
K
Hveem
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Lars
L
Vatten
Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Anne
A
Dørum
Section of Oncology, Department of Clinical Science, University of Bergen, Haukeland University Hospiltal, Jonas Lies veg 87, 5021, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Per E
PE
Lønning
Section of Oncology, Department of Clinical Science, University of Bergen, Haukeland University Hospiltal, Jonas Lies veg 87, 5021, Bergen, Norway. stian.knappskog@uib.no.|Department of Oncology, Haukeland University Hospital, Bergen, Norway. stian.knappskog@uib.no.
Stian
S
Knappskog
D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D015810:Linkage Disequilibrium; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
Cancer risk; Del1518; Endometrial cancer; MDM2; Ovarian cancer