Have questions? Visit https://www.reddit.com/r/SNPedia

rs2279744

From SNPedia

Associated with number of cancers and cancer prognosis
Orientationplus
Stabilizedplus
Geno Mag Summary
(G;G) 2.1 Generally more cancer prone
(G;T) 2 Generally more cancer prone; common
(T;T) 0 normal
ReferenceGRCh38 38.1/141
Chromosome12
Position68808800
GeneMDM2
is asnp
is mentioned by
dbSNPrs2279744
ebirs2279744
HLIrs2279744
Exacrs2279744
Varsomers2279744
Maprs2279744
PheGenIrs2279744
hapmaprs2279744
1000 genomesrs2279744
hgdprs2279744
ensemblrs2279744
gopubmedrs2279744
geneviewrs2279744
scholarrs2279744
googlers2279744
pharmgkbrs2279744
gwascentralrs2279744
openSNPrs2279744
23andMers2279744
23andMe allrs2279744
SNP Nexus

SNPshotrs2279744
SNPdbers2279744
MSV3drs2279744
GWAS Ctlgrs2279744
GMAF0.3691
Max Magnitude2.1

rs2279744, a variant in the promoter of the MDM2 gene and also known as "-410T-G", "SNP309", and "SNP309T>G", has been studied for several years to determine it's role in cancer origin and treatment. The interest primarily stems from the ability of the MDM2 protein to bind to and thereby enhance the degradation of the tumor suppressor protein known as p53. Studies on rs2279744 include:

  • rs2279744(G) carriers in individuals with cancer tend to develop such cancers on average 12 years earlier than those lacking this allele, and the frequency of rs2279744(G) was greatly increased in those who developed soft tissue sarcomas at a young age. [PMID 15550242]
  • Individuals with one or more rs2279744(G) alleles who are also carriers of the TP53 rs1042522(C) (arg at aa72) SNP tend to develop cancers earlier than rs2279744(T;T) homozygotes who carry the same p53 SNP. [PMID 16258005OA-icon.png]
  • rs2279744(T;T) individuals who have a mutant p53 (in their tumors) are at an increased risk of death (risk ratio [RR] of death = 2.33, 95% CI = 1.08 to 5.03). Tumor p53 status was not associated with breast cancer survival among rs2279744(G;T) or rs2279744(G;G) genotypes. [PMID 16818855]
  • rs2279744 showed no association with nonsmall cell lung cancer risk in a study of 1,787 Caucasian patients. However, a possible association between nonsmoking (G;G) homozygotes and a higher risk of nonsmall cell lung cancer was reported.[PMID 17957785]
  • A study in Chinese leukemia patients found that the rs2279744(G) allele was unexpectedly associated with reduced risk.[PMID 18313915]
  • Another study concludes that this SNP on its own has little or no effect on the risk of common cancers, but it might modify the time of tumor onset and prognosis. [PMID 17827408]
  • rs2279744(G;G) females are at a 2.76x increased risk (CI: 1.06-7.20, p=0.03) for endometrial cancer compared to (G;T) or (T;T) genotypes based on a study of 73 patients and matched controls.[PMID 17123590]
  • A study of 148 individuals with advanced nonsmall cell lung cancer (NSCLC) undergoing first-line chemotherapy, such as the irinotecan plus cisplatin regimen, concluded after multivariate analysis that the rs2279744(T;T) genotype was independently predictive for longer survival (HR = 1.742, p = .032).[PMID 18618574]
  • The rs2279744(G;G) genotype was associated with high grade breast cancer tumors (with an odds ratio of 1.64, CI:1.06-2.53, p=0.025) and greater nodal involvement (OR=2.51, CI:1.26-4.98, p=0.009), but was not associated with an earlier age of cancer diagnosis or even risk of breast cancer, in a study of ~300 Scottish Caucasian patients.[PMID 18828900OA-icon.png]
  • Around 300 cases each of melanoma, basal cell carcinoma, and squamous cell carcinoma were studied relative to this SNP. No significant associations were found between rs2279744 and any of these three types of skin cancer. However, compared with the (T;T) genotype, the adjusted odds ratios of having moles on the arms for (G;T) and (G;G) genotypes was 0.92 (CI: 0.78-1.08) and 0.68 (CI: 0.53-0.87), respectively (p, trend, 0.005).[PMID 18814047OA-icon.png]
  • rs2279744(G;G) women are diagnosed with melanoma 13 years earlier than women who carry one or no G alleles. Note that this SNP does not cause higher risk of melanoma; it affects only the age at diagnosis of melanoma in women and has no effect in men, as reported in the 23andMe blog 23andMe blog.
  • Odds ratio for (G;G) 3x, for (G;T) 2x, for breast cancer in a study of 124 Taiwanese patients, along with a correlation towards earlier occurence.[PMID 19144119OA-icon.png]
  • rs117039649, also known as SNP285C, a second MDM2 SNP found on the SNP305G allele (and only in Caucasians), reduces the risk of both ovarian and breast cancer among SNP309G holders (odds ratio 0.74 and 0.79, respectively), compared to SNP309G holders lacking this (second) SNP.[PMID 21316605]

23andMe blog rs2279744(G) has been associated with earlier onset for some cancers, including soft tissue sarcoma, diffuse large B-cell lymphoma, colorectal cancer, ovarian cancer and non-small cell lung cancer in women, and decreased survival in people with stomach and kidney cancer. But there is evidence for improved survival in women with ovarian cancer who have the G version of this SNP. Paradoxically, higher levels of the MDM2 protein (as would be expected with the G version of SNP rs2279744 shown to lead to earlier melanoma onset in the current study) have been associated with improved survival for melanoma.

  • rs2279744 is not associated with SLE in a study of Caucasians, African-Americans, and Asian children and adults.[PMID 19074170OA-icon.png]


[PMID 19521721OA-icon.png] Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms

OMIM164785
DescMOUSE DOUBLE MINUTE 2 HOMOLOG; MDM2
Variant
Relatedalso
[PMID 19707196OA-icon.png] The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

[PMID 19751436] Interaction of Helicobacter pylori with Genetic Variants in the MDM2 Promoter, is Associated with Gastric Cancer Susceptibility in Chinese Patients

[PMID 19837266] TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility



[PMID 20447891] MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

[PMID 20736372OA-icon.png] Human Papillomavirus Seropositivity Synergizes with MDM2 Variants to Increase the Risk of Oral Squamous Cell Carcinoma



[PMID 21051655] MDM2 as a Modifier Gene in Retinoblastoma

[PMID 20587610] Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection

OMIM164785
Desc
Variant0001
Relatedalso
[PMID 21843334OA-icon.png] TP53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma in Italian patients


[PMID 22251423] NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction


[PMID 22558411OA-icon.png] MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk


[PMID 16287156] Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer.


[PMID 17360557OA-icon.png] Haplotype structure and selection of the MDM2 oncogene in humans.


[PMID 17537232OA-icon.png] Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients.


[PMID 17634539] MDM2 SNP309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma.


[PMID 18332046] A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients.


[PMID 18433484OA-icon.png] Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene.


[PMID 18433491OA-icon.png] MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians.


[PMID 18798306OA-icon.png] Construction of a high resolution linkage disequilibrium map to evaluate common genetic variation in TP53 and neural tube defect risk in an Irish population.


[PMID 19237173] Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy.


[PMID 19470478OA-icon.png] Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans.


[PMID 19497887OA-icon.png] Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene.


[PMID 19542078] TP53 PIN3 and MDM2 SNP309 polymorphisms as genetic modifiers in the Li-Fraumeni syndrome: impact on age at first diagnosis.


[PMID 20452958OA-icon.png] Single-nucleotide polymorphisms in the p53 signaling pathway.


[PMID 20617153OA-icon.png] Detection of fetomaternal genotype associations in early-onset disorders: evaluation of different methods and their application to childhood leukemia.


[PMID 20922573OA-icon.png] Functional polymorphisms associated with disease-free survival in resected carcinoma of the esophagus.


[PMID 20979563] MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients.


[PMID 21240526] Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review.


[PMID 21268124] MDM2 SNP309 contributes to non-small cell lung cancer survival in Chinese.


[PMID 21305319OA-icon.png] Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li-Fraumeni syndrome.


[PMID 21437228OA-icon.png] Using epidemiology and genomics to understand osteosarcoma etiology.


[PMID 21841506] Combined effect of genetic polymorphisms in P53, P73, and MDM2 on non-small cell lung cancer survival.


[PMID 22004425] Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study.


[PMID 22180099] Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma.


GET Evidence
rs2279744
aa_change
aa_change_short
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.241935
summary Commonly called "SNP309", this non-coding variant increases binding specificity of transcription factor SP1, causing increased expression of MDM2 and decreased expression of P53, thereby increasing risk for tumorigenesis.



[PMID 23210739] Association of MDM2 and p53 Polymorphisms with the Advancement of Cervical Carcinoma


[PMID 23451111OA-icon.png] MDM2 SNP309 rs2279744 Polymorphism and Gastric Cancer Risk: A Meta-Analysis


[PMID 24175836] P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study


[PMID 24324286OA-icon.png] Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients


[PMID 24349246OA-icon.png] The T309G MDM2 Gene Polymorphism Is a Novel Risk Factor for Proliferative Vitreoretinopathy


[PMID 24427778OA-icon.png] ESR1 rs9340799 is associated with endometriosis-related infertility and in vitro fertilization failure


[PMID 23218882OA-icon.png] Significance of MDM2 and P14 ARF polymorphisms in susceptibility to differentiated thyroid carcinoma.


[PMID 23423487] Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy.


[PMID 24792886] Common variant on MDM2 contributes to endometrial cancer susceptibility: evidence based on 7 studies


[PMID 25054017OA-icon.png] Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk


[PMID 25218545] Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss


[PMID 25479941] Genetic association of single nucleotide polymorphisms in P53 pathway with gastric cancer risk in a Chinese Han population


ClinVar
Risk rs2279744(G;G)
Alt rs2279744(G;G)
Reference rs2279744(T;T)
Significance Other
Disease Accelerated tumor formation
Variation info
Gene MDM2
CLNDBN Accelerated tumor formation, susceptibility to
Reversed 0
HGVS NC_000012.11:g.69202580T>G
CLNSRC OMIM Allelic Variant
CLNACC RCV000014918.3,



[PMID 25734904OA-icon.png] Impact of TP53 Codon 72 and MDM2 SNP 309 Polymorphisms in Pancreatic Ductal Adenocarcinoma


[PMID 26135929] A Systematic Review and Meta-Analysis of Three Gene Variants Association with Risk of Prostate Cancer: An Update


[PMID 26224627OA-icon.png] Murine Double-Minute 2 Homolog Single Nucleotide Polymorphisms 285 and 309 in Cervical Carcinogenesis


[PMID 26373042] Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 Genes are Independent Predictors of Gastric Cancer Risk in a Northern Jiangsu Population (China)


[PMID 26471763] MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk


[PMID 25316267OA-icon.png] TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women


[PMID 27228500] Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma.


[PMID 27330794] Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects.


[PMID 27624283] MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer.


[PMID 27785069] Influence of MDM2 polymorphisms on squamous cell carcinoma susceptibility: a meta-analysis.