Expressive

rs11892031 (UGT1A): Bladder Cancer Risk Variant

Key takeaways

  • rs11892031 sits in the UGT1A gene cluster on chromosome 2q37.1, which encodes enzymes the body uses to process chemical compounds.
  • A large multi-stage GWAS linked this variant to bladder cancer risk at P=1x10^-7, just below the standard genome-wide significance threshold.
  • GTEx data show the variant increases UGT1A1 and UGT1A10 activity in stomach tissue but decreases UGT1A1 activity in the esophageal lining.
  • Evidence is preliminary; the variant has not reached genome-wide significance and has not been confirmed by independent replication in the available studies.
  • All genetic evidence is from European-ancestry cohorts.

Key takeaways

  • rs11892031 sits within the UGT1A gene cluster on chromosome 2q37.1, a set of genes encoding UDP-glucuronosyltransferase enzymes involved in the body's processing of various chemical compounds.
  • A large multi-stage bladder cancer GWAS linked this variant to risk at P=1x10^-7, a signal that narrowly missed the conventional genome-wide significance threshold of P<5x10^-8.
  • GTEx expression data from 953 donors show the variant's alternate allele increases UGT1A1 and UGT1A10 activity in stomach tissue but reduces UGT1A1 activity in the esophageal mucosal lining, pointing to tissue-specific regulation.
  • Evidence for this variant's role in bladder cancer is preliminary and has not been independently confirmed at genome-wide significance in the available studies.
  • All primary GWAS evidence comes from individuals of European descent.

What the research says A multi-stage genome-wide association study (GWAS) of bladder cancer, encompassing 3,532 cases and 5,120 controls in the primary scan and 8,381 cases and 48,275 controls across replication stages, identified rs11892031 on chromosome 2q37.1 within the UGT1A (UDP-glucuronosyltransferase 1A) gene cluster at a combined P-value of 1x10^-7 PMID 20972438. GTEx expression analyses from 953 tissue donors further link the alternate allele at this locus to increased expression of UGT1A1 and UGT1A10 in stomach tissue and to reduced expression of UGT1A1 in the mucosal lining of the esophagus GTEx Portal.

Reported associations

  • Bladder cancer susceptibility: In a multi-stage GWAS totaling over 11,900 cases and over 53,000 controls of European ancestry, this locus on 2q37.1 was associated with bladder cancer risk at P=1x10^-7 PMID 20972438.

Evidence quality The association with bladder cancer was identified at P=1x10^-7, falling just short of the standard genome-wide significance threshold of P<5x10^-8 PMID 20972438. In the same study, two other newly identified loci achieved full genome-wide significance at P=8x10^-12 and P=2x10^-11, whereas the UGT1A locus was reported as a sub-threshold finding PMID 20972438. The combined sample across all stages was substantial, totaling over 11,900 cases and 53,000 controls of European descent, but independent replication of this specific variant at genome-wide significance is not confirmed by the source material available for this entry. Overall, the evidence should be treated as preliminary. GTEx eQTL data provide biological plausibility for this locus but do not establish causal disease mechanisms GTEx Portal.

Tissue-specific expression effects

  • UGT1A1: The alternate allele is associated with increased expression in stomach tissue and reduced expression in the mucosal lining of the esophagus, indicating tissue-specific and directionally opposite regulation at this variant GTEx Portal.
  • UGT1A10: The alternate allele is associated with increased expression in stomach tissue GTEx Portal.
  • MROH2A: The alternate allele is associated with increased expression in stomach tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11892031?

rs11892031 is a single-nucleotide polymorphism (a type of single-letter difference in DNA) located on chromosome 2q37.1 within the UGT1A gene cluster. It has been studied primarily for its potential association with bladder cancer risk.

What do UGT1A8 and UGT1A10 genes do?

UGT1A8 and UGT1A10 are members of the UDP-glucuronosyltransferase gene family. These genes encode metabolic enzymes involved in the body's chemical processing of various compounds.

Is rs11892031 definitively linked to bladder cancer?

Not definitively. A large genome-wide association study found an association at P=1x10^-7, which is close to but below the standard genome-wide significance threshold of P<5x10^-8. Independent replication at genome-wide significance has not been confirmed in the available research.

How does rs11892031 affect UGT1A gene expression?

According to GTEx data from 953 tissue donors, the alternate allele of rs11892031 is associated with higher expression of UGT1A1 and UGT1A10 in stomach tissue but lower expression of UGT1A1 in the esophageal mucosal lining, indicating tissue-specific and directionally opposite effects on gene regulation.

What population was studied for rs11892031 and bladder cancer?

The primary GWAS evidence comes from individuals of European descent, with over 11,900 cases and over 53,000 controls across all stages of the study. Findings may not apply equally to other ancestry groups.