Rs6983267

rs6983267 is a SNP on chromosome 8q24, associated with increased risk for several 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.

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.

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%)

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.

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).

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.

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

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

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

rs6983267 confirmed to increase risk for colorectal cancer in a study of 561 patients.

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

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).

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: 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.

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

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