Pazopanib, a targeted cancer therapy, carries a real risk of liver enzyme elevation. The study behind this page found its strongest signal at HLA-B*57:01 (31% of carriers had severe elevation, versus 19% of non-carriers) — this page's AGER variant is a secondary signal from the same study, reported plainly as weaker.
Pazopanib is a targeted cancer therapy — a tyrosine kinase inhibitor — used in advanced renal cell carcinoma and soft tissue sarcoma. Like many targeted therapies, it carries a real risk of liver enzyme elevation (drug-induced liver injury), serious enough that patients on it have their liver function monitored regularly during treatment.
Xu et al. 2016 ran a pharmacogenetic study across 2,190 patients (1,188 in discovery, 1,002 in a separate confirmatory analysis) and found that HLA-B*57:01 carriers had substantially higher rates of severe liver enzyme elevation — 31% versus 19% in non-carriers. That is the paper's main, strongest, and most clinically discussed result.
The variant on this page, in AGER, is a secondary signal the same genome-wide association study flagged as a possible additional association — reported by the authors as warranting further investigation, not presented with anything like the confidence of the HLA-B*57:01 finding. This page keeps that distinction rather than presenting both as equivalent, because they are not.
Routine liver function monitoring during pazopanib treatment, established by prescribing guidelines, is what catches liver injury in practice — regardless of genotype at this or any locus. If HLA-B*57:01 status is relevant to a specific treatment decision, that is a conversation with the prescribing oncologist; this page's AGER variant is not established well enough to inform that conversation at all.
This page exists because AGER carries the specific reported trait ("pazopanib hepatotoxicity") from a real study, and the honest way to present a secondary, unconfirmed signal is to say so — not to imply it carries the same weight as the paper's primary, replicated finding.
Other drug hypersensitivity reactions on this catalogue linked to specific HLA alleles — abacavir hypersensitivity (HLA-B*57:01, the same allele as this paper's main finding, in a different drug context) is one example of how consistently this region of the genome turns up in drug safety pharmacogenomics.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Pazopanib-Associated Liver Injury comes down to these specific, well-studied positions — not a diagnosis.
Databases, guidelines and references
No. The study's primary, strongest finding is HLA-B*57:01, where carriers had a 31% rate of severe liver enzyme elevation versus 19% in non-carriers. The AGER variant on this page is a secondary signal from the same study, reported as needing further investigation.
This page does not recommend that. Routine liver function monitoring during treatment, per prescribing guidelines, is the established way liver injury is caught in practice. If HLA-B*57:01 testing is relevant to your specific situation, that is a conversation with your oncologist.
Because it is a real signal from a published, peer-reviewed pharmacogenetic study carrying this exact reported trait, and the honest approach is to present it with the same caveats the original authors gave it — not to omit it, and not to overstate it either.
It encodes the receptor for advanced glycation end-products, involved in inflammatory signalling. Its specific role, if any, in pazopanib-associated liver injury is not established by this study alone.
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