Smoking causes most bladder cancer, and blood in the urine is the symptom that matters. The variant here is unusual in a small way: it destroys a start codon, so what it does to the protein can be seen rather than guessed.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Bladder cancer is strongly linked to smoking and to certain occupational chemical exposures, and its most important symptom is blood in the urine — often painless, often intermittent, and never something to wait out.
Most common cancer variants sit in non-coding DNA and nobody can say exactly what they do. rs2294008 is different. It is a missense variant in PSCA — prostate stem cell antigen, despite the name, expressed in bladder tissue too — and it alters the start codon, predicted to truncate nine amino acids from the N-terminal signal sequence of the protein. A laboratory reporter assay showed the variant allele significantly reduced promoter activity, and resequencing found it to be the only common missense change in the gene.
So the chain from position to protein is visible here, which is rare enough on this site to be the reason the page exists.
Ordinary. The discovery scan compared 969 cases and 957 controls in Texas, validation followed in three further US populations and nine European ones, and across 6,667 cases and 39,590 controls the allelic odds ratio was 1.15 (95% CI 1.10–1.20, P = 2.14 x 10-10).
Fifteen per cent higher odds, in a disease whose dominant risk factor is smoking. That comparison is the useful one: no common variant here comes close to what tobacco does.
Not smoking, and taking blood in the urine seriously. Visible blood in urine warrants investigation even once, even if it clears up, and even if there is an easier explanation available. Occupational exposure to aromatic amines — historically in dye, rubber and leather work — matters too, and is worth mentioning to a doctor if it applies.
There is no screening programme and no role for this genotype in one.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 29 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Prokunina-Olsson L et al. 2026, Nature communications rs72826305 (CASC15), rs112204664 (CASC15), rs7076867 (COL13A1), rs7937265 (TNNT3), rs6910215 (CDKAL1), rs7145592 (MIPOL1), rs28698828 (near RAPGEF5), rs4832657 (near CYRIA), rs11738059 (SH3TC2-DT), rs67080241 (near RAPGEF1), rs11629846 (NR2F2-AS1), rs344028 (TIPARP-AS1) and 6 more — PMID:42706231
Verma A et al. 2024, Science (New York, N.Y.) rs5750711 (near APOBEC3A), rs142003747 (CASC15), rs17868304 (near UGT1A11P), rs2585181 (near PSCA) — PMID:39024449
Larsson SC et al. 2025, JNCI cancer spectrum rs3819177 (SLC14A1), rs17779033 (LINC01411), rs1814004 (MIPOL1) — PMID:39898788
Koutros S et al. 2023, European urology rs4743687 (SMC2), rs17863783 (UGT1A8) — PMID:37210288
Rashkin SR et al. 2020, Nature communications rs76088467 (CASC15) — PMID:32887889
Galesloot TE et al. 2022, European urology oncology rs12885353 (G2E3) — PMID:34353775
2026-08-08 · Prokunina-Olsson L, et al. Nature Communications 2026, PMID:42706231
Newly curated by the GWAS Catalog: 141 associations across 1 trait ("Bladder cancer"), from Prokunina-Olsson L, et al. in Nature Communications, 2026. Sample in the catalogue's record: 30,156 cases and 1,527,568 controls. Of its 70 positions, 33 already have pages here — 16 on the Bladder Cancer page; 1 on the Lung Cancer page; 1 on the Ulcerative Colitis page — including rs2294008 (PSCA), rs10094872 (MYC), rs2242652 (TERT). Put together by code from the catalogue's records; for anything more, follow the link to the paper. PMID:42706231.
2026-08-08 · Prokunina-Olsson L, et al. Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk. Nature Communications. 2026. PMID:42706231
Largest bladder cancer GWAS meta-analysis finds 70 risk loci, 43 new, tied to smoking biology
A multi-population meta-analysis of 32,470 bladder cancer cases and 1,753,462 controls identified 70 independent risk loci, 43 of them newly reported. A 70-marker polygenic risk score raised the area under the curve from 0.71 to 0.75 (HR=1.63 per standard deviation). The study's central mechanistic finding involves the 15q25.1 variant rs71581744, which co-localizes with tissue-specific CHRNA3 expression, modulates mRNA stability, and associates with risk of muscle-invasive bladder cancer specifically among current smokers -- direct evidence that germline genetics shapes smoking-driven bladder cancer risk, not just smoking exposure itself. This site's own bladder cancer page currently carries three variants (PSCA, CCNE1, TMEM129) from earlier, smaller GWAS efforts; rs71581744 and the other 42 novel loci from this new study were not yet indexed in GWAS Catalog's association records with bladder-cancer-specific p-values at the time of writing, so no new variant page was added -- this entry documents the study at the condition level rather than overstating single-SNP evidence this site could not independently verify.
2026-06-13 · Comprehensive genome-wide association study into multiple recurrence and progression risk in non-muscle invasive bladder cancer. Cancer Genetics. 2026. DOI:10.1016/j.cancergen.2026.06.004
In bladder cancer that keeps coming back, one variant predicts who responds to BCG treatment
This site's bladder cancer page already covers a 2026 study of overall bladder cancer risk; this is a different question -- not who gets bladder cancer, but who has non-muscle invasive bladder cancer (NMIBC) that keeps recurring or progresses to the more dangerous muscle-invasive form. Analyzing 5,009 patients across 8 cohorts from the Netherlands, UK, Canada and Spain, with 4,237 total recurrences observed, the study found no genome-wide significant associations with recurrence or progression in the overall population. But stratifying specifically by treatment with Bacillus Calmette-Guerin (BCG, the standard immunotherapy for NMIBC) revealed two genome-wide significant loci for recurrence-free survival in BCG-treated patients, the strongest being rs72744118, an intron variant in DISP-1 (hazard ratio 0.43, meaning carriers had less than half the recurrence risk; P=5.8x10^-10). Gene prioritization from this and colocalization analyses identified 16 candidate genes with expression tied to NMIBC outcomes in an independent validation cohort (UROMOL). This is the largest GWAS of NMIBC prognosis to date, and the DISP-1 finding is specifically about predicting treatment response, not baseline risk -- a genuinely different, clinically actionable angle from what this site's bladder cancer page currently covers.
The variant. Wu et al. conducted a GWAS in 969 bladder cancer cases and 957 controls from Texas, evaluated 60 SNPs in three additional US populations, and validated the top signal in nine European populations. Across all subjects (6,667 cases, 39,590 controls) rs2294008 gave an allelic odds ratio of 1.15 (95% CI 1.10–1.20, P = 2.14 x 10-10). The variant alters the start codon of PSCA and is predicted to truncate nine amino acids from the N-terminal signal sequence of the primary translation product; an in vitro reporter assay showed the variant allele significantly reduced promoter activity, and resequencing of the region established it as the only common missense SNP in the gene.
Context. Other established bladder cancer susceptibility loci include NAT2 slow-acetylator genotypes and the GSTM1 null genotype, both carcinogen-metabolism genes whose effects interact with smoking — a cleaner gene-environment story than most, and one where the environmental term dominates. Tobacco smoking accounts for a large share of cases; occupational exposure to aromatic amines is the classic non-smoking cause.
Clinical position. Visible haematuria is investigated with imaging and cystoscopy; management depends on whether disease is non-muscle-invasive or muscle-invasive, and surveillance after treatment is intensive because recurrence is common. No genotype enters diagnosis, staging, treatment or surveillance.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Bladder Cancer comes down to these specific, well-studied positions — not a diagnosis. 34 positions are linked to this page; the ones this page's own text discusses are shown first.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 3 of 34 linked studies with a resolved discovery ancestry.
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Bladder Cancer. MyGeneLog™. https://www.mygenelog.com/conditions/bladder-cancer
Its mechanism is visible. It changes the start codon of PSCA, is predicted to shorten the protein's signal sequence, and reduced promoter activity in a laboratory assay. Most common cancer variants sit in non-coding DNA where nobody can say what they do.
It is not close. This variant carries about 15% higher odds; smoking is the dominant cause of bladder cancer. The genetics here is interesting; the cigarette is the risk factor.
Blood in the urine — even once, even painless, even if it goes away. It has many causes, most of them not cancer, and all of them are better found than assumed.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.