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rs12913975

From SNPedia

Orientationplus
Stabilizedplus
Make rs12913975(A;A)
Make rs12913975(A;G)
Make rs12913975(G;G)
ReferenceGRCh38 38.1/141
Chromosome15
Position66764823
GeneSMAD6
is asnp
is mentioned by
dbSNPrs12913975
ebirs12913975
HLIrs12913975
Exacrs12913975
Varsomers12913975
Maprs12913975
PheGenIrs12913975
hapmaprs12913975
1000 genomesrs12913975
hgdprs12913975
ensemblrs12913975
gopubmedrs12913975
geneviewrs12913975
scholarrs12913975
googlers12913975
pharmgkbrs12913975
gwascentralrs12913975
openSNPrs12913975
23andMers12913975
23andMe allrs12913975
SNP Nexus

SNPshotrs12913975
SNPdbers12913975
MSV3drs12913975
GWAS Ctlgrs12913975
GMAF0.1584
Max Magnitude
? (A;A) (A;G) (G;G) 28
rs12913975 is an A/G single nucleotide polymorphism (SNP) of the SMAD6 gene that has been associated with the prognosis of non-small cell lung cancer (NSCLC) patients. The most common nucleotide or 'major allele' of this SNP is G, which is also the dominant allele. The minor allele is A, which according to data from the 1000 Genomes project occurs in the sampled population at a frequency of 15.8% (observed 345 times in 2183 people). HapMap data (July 2005) from 1208 individuals from 13 populations included population specific genotype frequencies for this SNP dbSNP.

A 2011 study published by Li et al. examined 33 SNPs in 13 TGF-beta pathway genes to estimate the effect of genotype on brain metastasis in 116 NSCLC patients. The authors found that NSCLC patients with the G/G genotype of the rs12913975 SNP had a significantly increased risk of brain metastasis compared to patients with the A/G genotype over the two years following initial time of lung cancer diagnosis (hazard risk: 2.540, 95% confidence interval: 1.204-5.359, p = 0.014). Hazard ratios and confidence intervals were estimated using cox proportional hazards model for the multivariate survival analyses adjusted for sex, age, clinical stage, tumor histology, Karnofsky performance status, and smoking status. A two-tailed t- test was used to determine significance of associations. This finding may allow clinicians to use the rs12913975 SNP as a measure of an NSCLC patients’ risk of developing brain metastasis. It is not known whether this SNP plays a functional role in the potential of NSCLC tumors to metastasize to the brain. However, the SNP is located in the SMAD6 gene, an inhibitor of TGF-beta signaling that is a pathway affected in different cancers, so this may in fact be a functional variant PMID: 23284751.

In 2011 Lin et al. determined the effect of genotype on survival in 598 advanced-stage NSCLC patients across 227 SNPs in 23 TGF-beta pathway-related genes to estimate. The authors identified the rs12913975 SNP as a genetic variant significantly associated with the overall survival of NSCLC patients (hazard risk: 1.29, 95% confidence interval: 1.05-1.59, p = 0.01). Furthermore, they found that the G/G allele of this SNP had a significant positive effect on the survival of NSCLC patients using chemoradiation (hazard risk: 0.61, 95% confidence interval: 0.42-0.90, p = 0.01), but that this trend was not significant when patients used only chemotherapy (hazard risk: 0.76, 95% confidence interval: 0.56-1.02, p = 0.29). Hazard ratios and confidence intervals were estimated using cox proportional hazards model for the multivariate survival analyses adjusted for age, sex, ethnicity, smoking status, clinical stager, pretreatment PS, and therapy modality. A two-tailed chi-squared or Fisher’s exact test was used to determine significance of associations. PMID: 21515830