MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer.
Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01-1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00-1.45) and among females (OR = 1.32; 95% CI = 1.01-1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00-1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009).
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.|Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
Reham
R
Helwa
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.|Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
Liv B
LB
Gansmo
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
Pål
P
Romundstad
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
Kristian
K
Hveem
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
Lars
L
Vatten
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Bríd M
BM
Ryan
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Curtis C
CC
Harris
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.|Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
Per E
PE
Lønning
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.|Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.
Stian
S
Knappskog
D001741:Black or African American; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D000090063:Proto-Oncogene Mas; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D044465:White People
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2