Rs6983267

rs6983267 is a SNP on chromosome 8q24, associated with increased risk for several [PMID 19047180] cancers, particularly prostate cancer. In studies dividing the 8q24 region, this SNP falls in region 3.

In a study of over 3,600 Caucasians with prostate cancer, rs6983267 is one of five SNPs used (with family history as a sixth factor) to cumulatively predict overall risk. On their own, the rs6983267(G;G) and (G;T) risk genotypes yield an odds ratio for developing prostate cancer of 1.37 (CI: 1.18-1.59, p=3.4-10e-5) and may account for 22.2% of population attributable risk.10.1056/NEJMoa075819

The increased risk of developing prostate cancer associated with rs6983267 now appears to be independent of the risk associated with its close neighbor, rs1447295. The odds ratio for heterozygotes is estimated to be 1.26 (CI: 1.13 - 1.41), and for homozygotes, 1.58 (CI: 1.40 - 1.78), compared to the homozygote rs6983267(T;T) genotype. [PMID 17401363]

[1] The rs1447295 location could be responsible for about seven percent of prostate cancer cases in white men of north European descent. Thus, taken together with rs6983267, these two genetic changes could account for as much as one quarter of prostate cancer cases in white men. The increased risk conferred by these loci was observed for all age groups studied.

cancer related according to this blog

We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% vs. 9%) [PMID 17826675]

In a study of 1,563 patients of European ancestry, this SNP was designated as the representative of a prostate cancer risk region termed "locus 2", with an odds ratio of 1.70 (CI: 1.39-2.07) for carriers of a risk genotype. Two other regions of chromosome 8q24 were also studied.[PMID 17925536]

In follow-up studies looking at disease severity (and not just overall risk), this SNP is reported to account for the risk (from region 3) of advanced prostate cancer. A meta-analysis of 10+ studies comprising over 15,000 prostate cancer patients concluded that the odds ratio for rs6983267(G) allele carriers is 1.25 (CI: 1.24-1.26).[PMID 18231127]

A study of 561 patients with colon cancer has found that rs6983267(G;T) and (G;G) genotypes have an age-adjusted odds ratio of 1.39 (CI:1.03-1.88) and 1.68 (CI:1.21-2.33), respectively, for the development of that disease compared to (T;T) genotypes.[PMID 18268117]

[PMID 17618284] rs6983267 P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively with colorectal adenoma

[PMID 18056436] associated with risk of colorectal cancer: Inheriting the risk variant at both this SNP and rs4779584 is estimated to increase the overall risk of developing colorectal cancer about 3 fold. The authors of this study are quoted as saying that "the lifetime risk [of bowel cancer] is about 5% in the UK so it's going up to 7% or so if you've got both bad copies of a variant." nature

[PMID 18362937] rs6983267 confirmed to increase risk for colorectal cancer in a study of 4,000 UK cases.

[PMID 18268117] rs6983267 confirmed to increase risk for colorectal cancer in a study of 561 patients.

[PMID 18535017] rs6983267 confirmed to increase risk for colorectal adenomas in a pooled analysis of 2,500+ cases.

[PMID 18990762] rs6983267 associated with smoking-related upper aerodigestive tract cancers including oropharynx and larynx, also lung cancer and liver cancer, but it was inversely associated with bladder cancer (OR 0.335, CI: 0.14-0.83).

[PMID 18726982] In a study of Japanese men, the rs6983267(G) allele did not show significant association with susceptibility to prostate cancer (PC vs. non-PC: p = 0.967, OR 1.00; CI: 0.83-1.21). However, it was associated with disease in non-aggressive PC (non-aggressive PC vs. normal controls: p = 0.0068, OR 1.43; CI: 1.10-1.85).

cancer-genetics these snps influence genetic risk for prostate cancer

• the haplotype rs6983267 rs1016343 rs4242384
• rs7501939
• rs1859962
• rs2660753
• rs9364554
• rs6465657
• rs10993994
• rs7931342
• rs2735839
• rs5945619
• rs10993994

[PMID 18839428] colorectal cancer rs10505477 and rs6983267 yielded allelic p-values of 1.42 x 10(-7) and 2.57 x 10(-7), respectively with OR=1.50 (95% CI: 1.29-1.75). Risk region was delineated by SNPs rs10505477 and rs7014346 and comprised 17 kb

blog discussion of the molecular biology

GWAS
SNP	rs6983267
PubMedID	[PMID 17401363]
Condition	Prostate cancer
Gene	Intergenic
Risk Allele	G
pValue	9.00E-013
OR	1.26
95% CI	1.13-1.41

GWAS snp
PMID	[PMID 18372905]
Trait	Colorectal cancer
Title	A genome-wide association study identifies colorectal cancer susceptibility loci on chromosome 10p14 and 8q23.3
Risk Allele
P-val	7.0000000000000004E-11
Odds Ratio	1.24 [1.17-1.33]

GWAS snp
PMID	[PMID 18264097]
Trait	Prostate cancer
Title	Multiple newly identified loci associated with prostate cancer susceptibility
Risk Allele	G
P-val	9E-13
Odds Ratio	1.42 [NR]

GWAS snp
PMID	[PMID 18264096]
Trait	Prostate cancer
Title	Multiple loci identified in a genome-wide association study of prostate cancer
Risk Allele	G
P-val	7.0000000000000001E-12
Odds Ratio	1.28 [1.15-1.45]

[PMID 19520795] Novel Single Nucleotide Polymorphism Associations with Colorectal Cancer on Chromosome 8q24 in African and European Americans

[PMID 19528667] Association of chromosome 8q variants with prostate cancer risk in Caucasian and Hispanic Men

[PMID 19562729] Common variants in 8q24 are associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry

[PMID 19561607] The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer

[PMID 19561604] The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling

[PMID 19602258] Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men

[PMID 19786869] Recent insights into the pathogenesis of colorectal cancer

[PMID 19843678] Enrichment of Low Penetrance Susceptibility Loci in a Dutch Familial Colorectal Cancer Cohort

[PMID 19857256] Association between an 8q24 locus and the risk of colorectal cancer in Japanese

[PMID 19895682] No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue

[PMID 20065031] Upregulation of c-MYC in Cis Through a Large Chromatin Loop Linked to a Cancer Risk-Associated SNP in Colorectal Cancer Cells

[PMID 20530476] Risk of Genome-Wide Association Study-Identified Genetic Variants for Colorectal Cancer in a Chinese Population

[PMID 20627891] An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer

[PMID 20638935] Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype

[PMID 20659471] Genetic Heterogeneity in Colorectal Cancer Associations in Americans of African vs. European Descent

[PMID 21051319] Risk of Urinary Bladder Cancer is Associated with 8q24 Variant rs9642880[T]: Results from the Los Angeles-Shanghai Case-Control Study

[PMID 21086507] GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP)

[PMID 21097774] Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome

[PMID 21119214] Colorectal Cancer Susceptibility Loci in a Population-Based Study: Associations with Morphological Parameters

[PMID 21129217] Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis

[PMID 21229559] Chromosome 8q24 variants are associated with prostate cancer risk in a high risk population of African ancestry

[PMID 21242260] Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population

[PMID 21567271] Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

[PMID 21722176] Association of 8q24.21 locus with the risk of colorectal cancer: A systematic review and meta-analysis

GWAS snp
PMID	[PMID 21743057]
Trait
Title	Genome-wide association study identifies new prostate cancer susceptibility loci.
Risk Allele	G
P-val	0.000009
Odds Ratio	1.2000 [1.11-1.32]

[PMID 21308149] Impact of genotyping on outcome of prostatic biopsies: a multicenter prospective study

[PMID 22067658] Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

[PMID 22070222] The multi-cancer marker, rs6983267, located at region 3 of chromosome 8q24, is associated with prostate cancer in Greek patients but does not contribute to the aggressiveness of the disease

[PMID 22070650] Meta-Analysis of Epidermal Growth Factor Polymorphisms and Cancer Risk: Involving 9,779 Cases and 15,932 Controls

[PMID 22234922] 8q24 risk alleles in West African and Caribbean men

[PMID 22275265] Common genetic variants in the 8q24 region and risk of papillary thyroid cancer

[PMID 22282540] Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24

[PMID 22367214] Characterization of gene-environment interactions for colorectal cancer susceptibility loci

[PMID 22434246] Increased Risk for CRC in Diabetic Patients with the Nonrisk Allele of SNPs at 8q24

[PMID 22457859] Single nucleotide polymorphisms in colorectal cancer: associations with tumor site and TNM stage

[PMID 22505654] GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes

[PMID 22583965] Association of common variations of 8q24 with the risk of prostate cancer in Koreans and a review of the Asian population

[PMID 22486879] Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non-risk allele colorectal cancer associated with insulin growth factor 2 receptor expression