Expressive

rs12322335 (TROAP-AS1): Cancer Predisposition Variant

Key takeaways

  • rs12322335 sits in TROAP-AS1, a long non-coding antisense RNA gene, and was identified as a candidate locus in a cancer predisposition study of approximately 500,000 UK Biobank participants.
  • The ALT allele is linked to increased C1QL4 gene expression in thyroid, prostate, minor salivary gland, and brain hippocampus tissue.
  • The same allele is associated with increased PRPH expression in brain hypothalamus, spinal cord (cervical), and hippocampus.
  • The ALT allele also increases DNAJC22 expression in sun-exposed lower-leg skin.
  • Evidence for cancer associations is from a single study without independent replication in the provided sources, and should be considered preliminary.

Key takeaways

  • rs12322335 sits in TROAP-AS1, a long non-coding antisense RNA gene, and was identified as a candidate locus in a cancer predisposition study of approximately 500,000 UK Biobank participants.
  • The ALT allele is linked to increased C1QL4 gene expression in thyroid, prostate, minor salivary gland, and brain hippocampus tissue.
  • The same allele is associated with increased PRPH expression in brain hypothalamus, spinal cord (cervical), and hippocampus.
  • The ALT allele also increases DNAJC22 expression in sun-exposed lower-leg skin.
  • Evidence for cancer associations is from a single study without independent replication in the provided sources, and should be considered preliminary.

What the research says A combined proteome-wide and genome-wide association study (PWAS/GWAS) of cancer predisposition (PWAS evaluates alterations to protein function; GWAS scans broadly for associated genetic variants) across approximately 500,000 UK Biobank participants identified the TROAP-AS1 locus as a candidate cancer risk region spanning nine cancer types and pan-cancer (Brandes N, Linial N, Linial M; Scientific Reports, 2021); specific per-variant effect sizes or p-values for this locus are not available from the provided text excerpt. GTEx v11 eQTL data (953 donors, FDR less than 0.05) shows the ALT allele is associated with increased C1QL4 expression in thyroid (p=1.2e-42), prostate (p=4.3e-14), brain hippocampus (p=5.0e-9), and minor salivary gland (p=2.0e-7), and with increased PRPH expression in brain hypothalamus (p=1.8e-11), spinal cord cervical c-1 (p=3.3e-10), and hippocampus (p=2.1e-8) GTEx Portal. The same allele is associated with increased DNAJC22 expression in sun-exposed lower-leg skin (p=2.3e-13) GTEx Portal.

Reported associations

  • Cancer predisposition: Identified as a candidate locus in a PWAS/GWAS analysis of nine cancer types and pan-cancer across approximately 500,000 UK Biobank participants; specific effect size and p-value for this variant are not available from the provided text (Brandes N, Linial N, Linial M; Scientific Reports, 2021).
  • C1QL4 gene expression: ALT allele associated with increased expression in thyroid (p=1.2e-42), prostate (p=4.3e-14), brain hippocampus (p=5.0e-9), and minor salivary gland (p=2.0e-7) GTEx Portal.
  • PRPH gene expression: ALT allele associated with increased expression in brain hypothalamus (p=1.8e-11), spinal cord cervical c-1 (p=3.3e-10), and hippocampus (p=2.1e-8) GTEx Portal.
  • DNAJC22 gene expression: ALT allele associated with increased expression in sun-exposed lower-leg skin (p=2.3e-13) GTEx Portal.

Evidence quality The cancer predisposition association comes from a single large-scale study using approximately 500,000 UK Biobank participants, employing a combined PWAS and GWAS approach to implicate 145 genomic loci across nine cancer types and pan-cancer (Brandes N, Linial N, Linial M; Scientific Reports, 2021); no PMID was available in the provided study metadata, no specific effect size or p-value for this variant is available in the provided text excerpt, and no independent replication data is present in the provided sources, so the cancer association should be treated as preliminary. The GTEx v11 eQTL associations (953 donors, FDR less than 0.05) are statistically robust: the strongest signal is C1QL4 expression in thyroid (p=1.2e-42), and all eight tissue-gene associations clear the FDR threshold GTEx Portal. These eQTL data describe gene regulation mechanisms, not clinical outcomes; the biological link between altered expression of C1QL4, PRPH, and DNAJC22 and any disease phenotype is not established by the provided data.

Tissue-specific expression effects

  • C1QL4: The ALT allele is associated with increased expression in thyroid (strongest signal, p=1.2e-42), prostate, minor salivary gland, and brain hippocampus GTEx Portal.
  • PRPH: The ALT allele is associated with increased expression in brain hypothalamus, spinal cord (cervical c-1), and hippocampus GTEx Portal.
  • DNAJC22: The ALT allele is associated with increased expression in sun-exposed lower-leg skin GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Screening

  • prostate cancer screening discussion Moderate

    Variant associated with 1.13x increased prostate cancer risk (p=1e-8, n=125,644).

    Discuss baseline age and frequency for PSA/DRE screening based on genetic and family risk factors.

Frequently asked questions

What is TROAP-AS1?

TROAP-AS1 is a long non-coding RNA gene, meaning it is transcribed into RNA but does not produce a protein. The '-AS1' suffix indicates it is classified as an antisense transcript, read from the complementary strand of DNA in the TROAP gene region.

Is rs12322335 linked to cancer?

A large study of approximately 500,000 UK Biobank participants identified the TROAP-AS1 locus as a candidate cancer predisposition site across nine cancer types and pan-cancer. Specific effect sizes and p-values for this variant are not available from the provided study excerpt, and independent replication is absent from the provided sources, so this association should be considered preliminary.

What genes does rs12322335 regulate?

GTEx eQTL data shows the ALT allele of this variant is associated with increased expression of C1QL4 (in thyroid, prostate, minor salivary gland, and brain hippocampus), PRPH (in brain hypothalamus, spinal cord, and hippocampus), and DNAJC22 (in sun-exposed skin).

What is an eQTL?

An eQTL (expression quantitative trait locus) is a genetic variant statistically associated with how much a nearby gene is expressed, meaning how actively that gene is being read and converted into RNA. eQTL data reveals potential mechanisms of gene regulation but does not by itself indicate a clinical outcome.

How strong is the evidence for this variant?

The cancer predisposition link comes from a single large study and lacks independent replication in the provided sources, making it preliminary. The gene expression associations from GTEx v11 are statistically robust, with the strongest signal being C1QL4 in thyroid tissue at p=1.2e-42 across 953 donors.