Expressive

rs10096351 (PCAT1/CASC8): 8q24 Cancer Risk Locus

Key takeaways

  • rs10096351 lies in the 8q24 chromosomal region near PCAT1, POU5F1B, and CASC8, a known pleiotropic cancer risk locus
  • Studies confirm significant shared genetic risk between breast and prostate cancer at this chromosomal region across multiple ancestries
  • A combined meta-analysis of 277,896 cases and 901,858 controls found 91 new genome-wide significant loci for these two cancers together
  • Risk variants in this region mostly fall in regulatory DNA, not protein-coding genes, pointing to a gene-regulation mechanism
  • The 8q24 locus has been studied in both East Asian and European populations with consistent findings across biobanks

Key takeaways

  • rs10096351 lies within the 8q24 chromosomal region, near PCAT1 (prostate cancer associated transcript 1), POU5F1B, and CASC8 (cancer susceptibility 8), a locus cited in pan-cancer genomic research as a known pleiotropic cancer risk zone
  • Large-scale studies across East Asian and European populations have confirmed significant positive genetic correlation between breast and prostate cancer, suggesting shared inherited risk at this region
  • A combined meta-analysis of 277,896 breast and prostate cancer cases and 901,858 controls identified 91 new genome-wide significant loci, with this chromosomal area among established risk regions
  • Risk variants near this locus tend to fall in non-coding regulatory DNA rather than in protein-coding sequences
  • The source studies for this entry do not individually name rs10096351 as a directly tested variant; associations described here reflect the broader 8q24 evidence base cited in those works

What the research says The 8q24 region is cited as a known pleiotropic cancer-associated locus in a pan-cancer genome-wide association study (GWAS) meta-analysis examining 250,015 East Asian participants from BioBank Japan and 377,441 European participants from UK Biobank. A large breast cancer GWAS covering 122,977 cases and 105,974 controls of European ancestry, plus 14,068 cases and 13,104 controls of East Asian ancestry, found that credible risk variants at newly identified cancer loci predominantly lie in distal regulatory elements, with heritability of breast cancer enriched two- to fivefold in regulatory genomic features compared to the genome-wide average.

Reported associations

  • Multiple cancer types (8q24 locus): This region is cited as a known pleiotropic cancer risk locus in a pan-cancer GWAS meta-analysis of over 627,000 participants across East Asian and European populations, which identified ten new genome-wide significant cancer risk variants across 13 cancer types
  • Breast cancer: A large-scale GWAS identified 65 new breast cancer risk loci at p < 5x10-8 in over 136,000 cases; credible risk SNPs are enriched at binding sites for transcription factors FOXA1, ESR1, GATA3, E2F1, and TCF7L2, and candidate target genes at these loci overlap with somatic driver genes in breast tumors
  • Prostate cancer (shared genetic architecture with breast cancer): Significant positive genetic correlations between breast and prostate cancer were confirmed in both East Asian and European populations, and a combined meta-analysis of 277,896 cases and 901,858 controls identified 91 new genome-wide significant loci at p < 5x10-8

Evidence quality The studies informing this entry are among the largest cancer genomics efforts published to date. The pan-cancer GWAS combined BioBank Japan (n=250,015 East Asians, including 61,465 cancer cases) and UK Biobank (n=377,441 Europeans, including 43,098 cancer cases) data with replication analyses. The breast cancer GWAS performed fixed-effects meta-analysis across more than 250,000 participants with approximately 21 million imputed variants using the 1000 Genomes Project Phase 3 reference panel. Both studies applied genome-wide significance thresholds (p < 5x10-8) and multi-population designs to support generalizability of findings. A critical limitation is that neither source study names rs10096351 as a directly tested variant in the available text; effect sizes and p-values specific to this SNP are not reported here, and the associations described reflect the 8q24 region as cited in these works rather than per-variant findings for rs10096351.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10096351?

rs10096351 is a single nucleotide polymorphism (a one-letter variation in DNA) located in the 8q24 chromosomal region near the genes PCAT1, POU5F1B, and CASC8. This region has been repeatedly identified in large-scale cancer genomic studies as a risk locus associated with multiple cancer types.

Which cancers are linked to the 8q24 region near PCAT1 and CASC8?

The 8q24 region is described in pan-cancer research as a pleiotropic risk locus, meaning it is associated with more than one cancer type. Large-scale studies covering over 627,000 participants have found particularly strong connections to breast cancer and prostate cancer, with evidence of shared genetic architecture between the two.

Are breast cancer and prostate cancer genetically related?

Yes, large-scale genomic studies have confirmed a significant positive genetic correlation between breast and prostate cancer across both East Asian and European populations. A combined meta-analysis of 277,896 cases and 901,858 controls identified 91 new genome-wide significant loci shared between these cancers.

What does pleiotropic mean for a cancer risk variant?

A pleiotropic variant or region is one that influences more than one trait or condition. In cancer genetics, a pleiotropic locus can contribute to risk for multiple different cancer types. The 8q24 region is described as pleiotropic in pan-cancer research because associations have been reported across several distinct cancer types.

How are cancer risk loci like 8q24 discovered?

Researchers use genome-wide association studies (GWAS), which scan large numbers of genetic variants across groups of people with and without cancer. Studies informing this entry examined over 600,000 participants across multiple countries and ancestries to identify regions like 8q24 that appear more frequently in people diagnosed with cancer.