Skip to content

Hereditary cancer

Not a medical test — for research and educational use only

Yeliztli analyses consumer genotyping-array data (23andMe / AncestryDNA), which is not a clinical-grade test. Results are not diagnostic, are not clinically validated, and must not be used to make medical decisions. Array data is especially unreliable for rare, disease-causing variants. Always confirm any finding with an accredited clinical laboratory and discuss it with a qualified clinician or genetic counsellor before acting on it. See the Intended use & disclaimers page for the details and the evidence behind this warning.

The cancer module looks for inherited variants linked to hereditary-cancer syndromes, and separately estimates polygenic risk for a few common cancers.

What it looks at

A 28-gene hereditary-cancer panel, including BRCA1, BRCA2, TP53, PALB2, ATM, CHEK2, the Lynch-syndrome mismatch-repair genes (MLH1, MSH2, MSH6, PMS2), APC, MUTYH, PTEN, STK11, CDH1, and others. It also computes polygenic risk scores (PRS) for prostate, colorectal, and melanoma.

What you'll see

  • Monogenic findings — ClinVar Pathogenic/Likely-Pathogenic variants in panel genes, grouped by cancer syndrome, each with its ClinVar accession, review stars, inheritance pattern, and an evidence rating. For recessive genes, you're told whether you're a carrier versus affected. BRCA1/BRCA2 findings cross-reference the carrier module, where they also appear in a reproductive context. ClinVar lower-penetrance/risk-allele findings are stored under a distinct findings category from high-penetrance P/LP cancer-predisposition variants, although the current page displays both categories together.1
  • Polygenic scores — shown as a population percentile, never as a raw score, confidence interval, or absolute risk. This statement is specific to cancer PRS output: PRS percentiles are explicitly research-use-only and are kept separate from the optional monogenic absolute-risk context below.
  • Absolute-risk context (optional) — after explicit opt-in, the Cancer page can show a breast-cancer context card. It compares a general-population female lifetime-risk baseline from NCI SEER with published female-carrier penetrance estimates for BRCA1/BRCA2 Pathogenic/Likely-Pathogenic findings [1]. This is not a PRS-derived estimate and not a personalized clinical risk model.

Breast-cancer PRS is currently unavailable

The source-verified breast-cancer PRS77 [2] is not scored or reported. The bundled GRCh38 allele audit [3] records 39 multiallelic primary loci and 2 additional biallelic loci that are palindromic without trusted effect-allele strand provenance. The current sample schema does not preserve enough allele context to harmonize those loci safely. This is a runtime limitation, not an ancestry-calibration result; the percentile note below applies only to models that are scored.

Percentiles can be withheld

A polygenic percentile is only shown when the score is properly calibrated for your inferred ancestry. When it isn't, Yeliztli withholds the percentile rather than show a misleading number.

Good to know

  • A negative result does not rule out hereditary cancer risk — arrays type only specific variants, not whole genes.
  • Polygenic scores are derived mostly in European-ancestry cohorts; an ancestry-mismatch warning is shown when your inferred ancestry differs, and the per-component evidence is capped low.
  • MUTYH single-copy carriers are framed as carriers, not as affected.

How to read the absolute-risk context

The absolute-risk context is hidden until you opt in because it displays sensitive disease-risk numbers. When shown, read it as context for clinical follow-up, not as a diagnosis or a complete personal risk calculation.

  • Population lifetime risk is the general-population baseline used for comparison. In this card it comes from NCI SEER's female breast-cancer statistics; it is not computed from your genotype.
  • Carrier penetrance is the estimated proportion of people with a specific pathogenic genotype who develop the condition over a defined time window.
  • Cumulative risk to age 80 means the estimated probability that a female BRCA1 or BRCA2 carrier is diagnosed with breast cancer by age 80 in the cited carrier-cohort study [1]. It is a group estimate, not your personal probability.
  • 95% CI means the study's 95% confidence interval around the estimate. It describes statistical uncertainty in the published estimate, not a guarantee that an individual's risk falls inside that range.

Sex-specific context matters. For XY/male samples, Yeliztli does not show the female BRCA1/BRCA2 cumulative-risk figures; it shows male-specific framing instead. If biological sex cannot be resolved from array data, sex-specific numeric penetrance is withheld.

References

[1] Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402-2416. PMID 28632866.

[2] Mavaddat N, et al. Prediction of breast cancer risk based on profiling with common genetic variants. Journal of the National Cancer Institute. 2015;107(5):djv036. PMID:25855707 (accessed 2026-08-03).

[3] Yeliztli cancer PRS panel version 1.2.0, breast-cancer PRS77 model_provenance.current_allele_audit in backend/data/panels/cancer_prs_weights.json (Ensembl Variation GRCh38 audit checked 2026-07-16; DOI:10.1093/database/bay119) (accessed 2026-08-03).

  1. Schmidt RJ, et al. Recommendations for risk allele evidence curation, classification, and reporting from the ClinGen Low Penetrance/Risk Allele Working Group. Genetics in Medicine. 2024;26(3):101036. PMID:38054408; DOI:10.1016/j.gim.2023.101036 (accessed 2026-07-31). ↩