|Determines prostate cancer risk; well researched|
|(G;G)||3.2||1.6x increased risk for prostate cancer; also other cancers|
|(G;T)||2.7||1.3x risk of prostate cancer; aspirin reduces risk of colorectal cancer|
|(T;T)||2||normal risk for cancers; aspirin reduces risk for colorectal cancer|
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. This SNP has also been reported to influence the cancer-risk-decreasing effect of aspirin.
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]
 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 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).
Chemoprevention: [PMID 24317174] This study of 840+ colorectal patients concluded that a lower risk of colorectal cancer was associated with the rs6983267(T) allele (additive adjusted OR 0.83, CI = 0.74 to 0.94; p trend = .002) for those taking aspirin. Compared with individuals with the GG genotype, taking aspirin led to adjusted odds ratios of colorectal cancer risk were 0.85 (CI = 0.69 to 1.04) for those with the GT genotype and 0.69 (95% CI = 0.54 to 0.87) for those with the TT genotype. No reduction in colorectal cancer incidence was seen for rs6983267(G;G) individuals taking aspirin compared to GG individuals not taking aspirin.
- the haplotype rs6983267 rs1016343 rs4242384
[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
|Title||A genome-wide association study identifies colorectal cancer susceptibility loci on chromosome 10p14 and 8q23.3|
|Odds Ratio||1.24 [1.17-1.33]|
|Title||Multiple newly identified loci associated with prostate cancer susceptibility|
|Odds Ratio||1.42 [NR]|
|Title||Multiple loci identified in a genome-wide association study of prostate cancer|
|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
|Title||Genome-wide association study identifies new prostate cancer susceptibility loci.|
|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
[PMID 22629442] Evaluation of allele-specific somatic changes of genome-wide association study susceptibility alleles in human colorectal cancers
[PMID 22733159] Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations
[PMID 17618282] A common genetic risk factor for colorectal and prostate cancer.
[PMID 17713544] Lack of a relationship between the common 8q24 variant rs6983267 and risk of chronic lymphocytic leukemia.
[PMID 17903305] A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study.
[PMID 17978284] Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus.
[PMID 18172290] Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution.
[PMID 18224312] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
[PMID 18274536] Genome-wide association studies: progress and potential for drug discovery and development.
[PMID 18349290] Association of genetic variants at 8q24 with breast cancer risk.
[PMID 18360876] Chromosome 8q24 markers: risk of early-onset and familial prostate cancer.
[PMID 18372901] Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
[PMID 18491292] Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations.
[PMID 18577746] Multiple loci with different cancer specificities within the 8q24 gene desert.
[PMID 18670647] Homozygous deletions and recurrent amplifications implicate new genes involved in prostate cancer.
[PMID 18682823] Canadian Urological Association, 63rd Annual Meeting, Edmonton, AB, June 22-25, 2008.
[PMID 18704501] Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers.
[PMID 18765558] Effect of genetic variability within 8q24 on aggressiveness patterns at diagnosis and familial status of prostate cancer.
[PMID 18768484] Family-based samples can play an important role in genetic association studies.
[PMID 18768513] Common 8q24 sequence variations are associated with Asian Indian advanced prostate cancer risk.
[PMID 18794092] Association of prostate cancer risk variants with clinicopathologic characteristics of the disease.
[PMID 18949397] The POU5F1P1 pseudogene encodes a putative protein similar to POU5F1 isoform 1.
[PMID 18973230] Breast cancer susceptibility alleles and ovarian cancer risk in 2 study populations.
[PMID 18974127] Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer.
[PMID 19011631] Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
[PMID 19058137] Clinical utility of five genetic variants for predicting prostate cancer risk and mortality.
[PMID 19104501] Prostate cancer genomics: towards a new understanding.
[PMID 19155440] Meta association of colorectal cancer confirms risk alleles at 8q24 and 18q21.
[PMID 19304784] Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.
[PMID 19357349] Association of common genetic variants in SMAD7 and risk of colon cancer.
[PMID 19366828] Evaluation of 8q24 and 17q risk loci and prostate cancer mortality.
[PMID 19366831] Analysis of recently identified prostate cancer susceptibility loci in a population-based study: associations with family history and clinical features.
[PMID 19395656] The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression.
[PMID 19434427] Analytical methods for inferring functional effects of single base pair substitutions in human cancers.
[PMID 19434657] Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19549807] Prostate cancer risk associated loci in African Americans.
[PMID 19549893] Evaluation of the 8q24 prostate cancer risk locus and MYC expression.
[PMID 19567509] Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes.
[PMID 19680443] Functional enhancers at the gene-poor 8q24 cancer-linked locus.
[PMID 19690179] Functional and clinical significance of variants localized to 8q24 in colon cancer.
[PMID 19822575] Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing.
[PMID 19916168] Genome-wide association studies--a summary for the clinical gastroenterologist.
[PMID 20039378] Estimation of genotype relative risks from pedigree data by retrospective likelihoods.
[PMID 20133699] Long-range enhancers on 8q24 regulate c-Myc.
[PMID 20158306] Variation at 8q24 and 9p24 and risk of epithelial ovarian cancer.
[PMID 20450899] Individual and cumulative association of prostate cancer susceptibility variants with clinicopathologic characteristics of the disease.
[PMID 20482849] NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations.
[PMID 20501757] Low-penetrance susceptibility variants in familial colorectal cancer.
[PMID 20584312] 8q24 sequence variants in relation to prostate cancer risk among men of African descent: a case-control study.
[PMID 20628624] Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
[PMID 20648012] Association studies on 11 published colorectal cancer risk loci.
[PMID 20690139] Meta-analysis of genome-wide and replication association studies on prostate cancer.
[PMID 20696899] TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions.
[PMID 20824129] Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis.
[PMID 21071539] Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations.
[PMID 21314996] Systematic search for enhancer elements and somatic allelic imbalance at seven low-penetrance colorectal cancer predisposition loci.
[PMID 21343373] Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence.
[PMID 21390317] Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.
[PMID 21437228] Using epidemiology and genomics to understand osteosarcoma etiology.
[PMID 21455501] Genetic variants on chromosome 8q24 and colorectal neoplasia risk: a case-control study in China and a meta-analysis of the published literature.
[PMID 21456070] GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP).
[PMID 21476894] Common variants of the thyroglobulin gene are associated with differentiated thyroid cancer risk.
[PMID 21538423] Early onset prostate cancer has a significant genetic component.
[PMID 21557270] Chromosome 8q24 variants are associated with prostate cancer risk in a high risk population of African ancestry.
[PMID 21945030] Amplification of the G allele at SNP rs6983267 in 8q24 amplicons in myeloid malignancies as cause of the lack of MYC overexpression?
[PMID 22045029] Relationship between 16 susceptibility loci and colorectal cancer phenotype in 3146 patients.
[PMID 22235025] Susceptibility genetic variants associated with early-onset colorectal cancer.
[PMID 22382457] Racial disparities in the association between variants on 8q24 and prostate cancer: a systematic review and meta-analysis.
[PMID 22561070] 8q24 and 17q Prostate cancer susceptibility loci in a multiethnic Asian cohort().
[PMID 22976378] The rs6983267 SNP Is Associated with MYC Transcription Efficiency, Which Promotes Progression and Worsens Prognosis of Colorectal Cancer
|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23118011] Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors
[PMID 22677538] The prostate cancer risk locus at 10q11 is associated with DNA repair capacity
[PMID 23359760] Single-nucleotide polymorphism associations for colorectal cancer in southern chinese population
|Title||Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-wide Meta-analysis.|
|Odds Ratio||1.13 [1.09-1.18]|
[PMID 23532531] Common Variants at 8q24 are Associated with Prostate Cancer Risk in Serbian Population
[PMID 23796952] CCAT2, a novel non-coding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
[PMID 24115145] No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotype
[PMID 24224612] Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a hispanic population
[PMID 24317174] Aspirin Use, 8q24 Single Nucleotide Polymorphism rs6983267, and Colorectal Cancer According to CTNNB1 Alterations
[PMID 24345439] Prostate cancer risk alleles are associated with prostate cancer tumor volume and prostate size
[PMID 24390711] Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer
[PMID 22821767] Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer.
[PMID 22848662] Polymorphisms on 8q24 are associated with lung cancer risk and survival in Han Chinese.
[PMID 22848671] Association of eleven common, low-penetrance colorectal cancer susceptibility genetic variants at six risk loci with clinical outcome.
[PMID 22999960] Much of the genetic risk of colorectal cancer is likely to be mediated through susceptibility to adenomas.
[PMID 23133607] Associations between gene expression variations and ovarian cancer risk alleles identified from genome wide association studies.
[PMID 23434150] Are the common genetic variants associated with colorectal cancer risk for DNA mismatch repair gene mutation carriers?
[PMID 23570689] Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.
[PMID 23628314] A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians.
[PMID 23723249] GWAS3D: Detecting human regulatory variants by integrative analysis of genome-wide associations, chromosome interactions and histone modifications.
[PMID 23776012] Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas.
[PMID 24801760] Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP
[PMID 24854447] Association analysis of colorectal cancer susceptibility variants with gastric cancer in a Chinese Han population
[PMID 24875374] Variation in the Association Between Colorectal Cancer Susceptibility Loci and Colorectal Polyps by Polyp Type
[PMID 24978480] A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis
|Title||Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies.|
|Odds Ratio||.29 [0.22-0.36] unit increase|
|Trait||Prostate cancer (early onset)|
|Title||Genome-wide association scan for variants associated with early-onset prostate cancer.|
|Odds Ratio||1.36 [NR]|
|Title||Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.|
|Odds Ratio||1.14 [1.10-1.18]|
[PMID 25939847] Association of common variants on chromosome 8q24 with gastric cancer in Venezuelan patients
[PMID 26451011] Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas
[PMID 26579801] Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results
[PMID 26853146] Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2.
[PMID 26885031] Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis.
[PMID 27432114] The rs6983267 SNP and long non-coding RNA CARLo-5 are associated with endometrial carcinoma.
[PMID 27689194] Single Nucleotide Polymorphisms within the 8Q24 Region are Not Associated with the Risk of Intraductal Papillary Mucinous Neoplasms of the Pancreas.