title: Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon.
abstract: MDM2 is a key regulator of the p53 tumor suppressor protein and is overexpressed in many human cancers. Two single nucleotide polymorphisms (SNPs) located in the MDM2 intronic promoter (P2) have been found to exert biological function. The G-allele of SNP309T>G; rs2279744 increases MDM2 transcription and has been linked to increased cancer risk. In contrast, the less frequent SNP285G>C; rs117039649, which is in complete linkage disequilibrium with SNP309 (generating a SNP285C/309G variant haplotype), has been related to reduced MDM2 transcription and to reduced risk of breast, endometrial and ovarian cancer. In this large population-based case-control study, we genotyped SNP309 and SNP285 in 10,830 individuals, including cases with cancer of the breast (n=1,717), colon (n=1,532), lung (n=1,331) and prostate (n=2,501), as well as 3,749 non-cancer controls. We found a slightly reduced risk for lung cancer among individuals harboring the SNP309TG/GG genotypes compared to the SNP309TT genotype (OR= 0.86; CI = 0.67-0.98), but this association was restricted to women (OR = 0.77; CI = 0.63-0.95) and was not present among men (OR = 0.91; CI = 0.77-1.08). Consistent with previous findings, we found a reduced risk for breast cancer among individuals carrying the SNP285GC/309GG genotype versus the SNP285GG/309GG genotype (OR = 0.55; CI = 0.33-0.93). In conclusion, our data support the hypothesis that the effects of both SNP285 and SNP309 status are tissue dependent.
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Liv B
authors.initials: LB
authors.lastname: Gansmo
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Pål
authors.initials: P
authors.lastname: Romundstad
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.forename: Lars
authors.initials: L
authors.lastname: Vatten
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012737:Sex Factors
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; SNP309; SNP309 cancer risk