The most common cancer in the world, and one of the least discussed. Its genetics was found by sequencing 2,636 Icelanders and imputing into a quarter of a million people — and one of the variants sits in TP53 itself.
Basal cell carcinoma is the most common cancer in humans, by a wide margin. It arises in the deepest layer of the epidermis, grows slowly, and almost never spreads to other organs — which is why it is both extremely common and rarely fatal.
That combination makes it easy to underrate. It is still a cancer, it still has to be removed, and it removes tissue from wherever it happened to start — very often a face.
A 2015 study sequenced the whole genomes of 2,636 Icelanders, giving 24,988,228 variants, then imputed them into 4,572 people with basal cell carcinoma and 266,358 controls.
That design is worth noticing. Rather than genotyping everyone at a fixed set of positions, it reads a smaller number of genomes completely and then infers the rest — which is how a population the size of Iceland can produce a study with a quarter of a million controls in it.
Four new susceptibility loci came out: 2p24 near MYCN (OR 0.76), 2q33 at CASP8–ALS2CR12 (OR 1.15), 8q21 at ZFHX4 (OR 0.70) and 10p14 near GATA3 (OR 0.74).
Fine mapping found that two variants correlated with the GATA3 signal fall in conserved binding sites for the GATA3 transcription factor itself — a rare case of a GWAS hit landing somewhere with an obvious mechanism.
rs78378222 is in TP53, the most-studied tumour suppressor gene there is — the gene whose loss is involved in a large share of all human cancers.
Most of what people know about TP53 concerns rare, high-penetrance mutations and Li–Fraumeni syndrome. This is a different object: a common variant in the same gene, contributing to a common cancer by a modest amount. Same gene, entirely different kind of finding, and they should not be read as though they were the same.
The dominant cause of basal cell carcinoma is ultraviolet exposure, and the dominant risk factor is having skin that burns. Neither of those is in dispute and neither is displaced by anything here.
There is no genetic test for basal cell carcinoma. It is diagnosed by looking at the skin and confirming with a biopsy, and it is prevented by sun protection. If a mark on your skin is new, changing, bleeding or not healing, that is a dermatologist rather than a genotype.
See also sun sensitivity and skin cancer risk, which covers the pigmentation side of this.
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 83 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.
Choquet H et al. 2024, Communications biology rs9271611 (near HLA-DQA1), rs55668940 (DCST1), rs7098111 (near LINC02674), rs9668178 (SSPN-AS1), rs11743151 (OSMR-DT), rs3845780 (STRN), rs35768603 (FOXP1), rs142388808 (IRF4), rs78663305 (near XCL2), rs4705928 (P4HA2), rs28765982 (RGS22), rs16982253 (near GACAT3) and 51 more — PMID:38182794
Seviiri M et al. 2022, Nature communications rs7498985 (GAS8), rs9878566 (TIPARP-AS1), rs10830255 (near NOX4), rs6989943 (RGS22), rs502803 (near HLA-DQA1), rs2849695 (near LINC00111), rs11961808 (near EXOC2), rs10102592 (near Y_RNA), rs10820610 (near SMC2), rs2082481 (SCAF1), rs12142181 (near RNA5SP45) — PMID:36496446
Verma A et al. 2024, Science (New York, N.Y.) rs9269080 (HLA-DRB9), rs79188822 (near RNU6ATAC37P), rs11586259 (near RHOU), rs76407406 (LINC02676), rs28410444 (RGS22), rs369593216 (near BNC2), rs6764416 (FOXP1), rs6547771 (near MRPL45P1), rs548082010 (CFL1) — PMID:39024449
2025-11-20 · Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer. NPJ Genomic Medicine. 2025. DOI:10.1038/s41525-025-00529-w
This is the largest genome-wide association study of high-grade serous ovarian cancer (HGSOC) to date, meta-analyzing over 22 million variants across 398,238 women from three major consortia (OCAC, UK Biobank, CIMBA). It found 8 novel risk variants across 7 loci, adding to 19 previously known regions. The most interesting single finding, biologically, is rs78378222-T, a variant in the 3' untranslated region (UTR) of TP53 -- the most famous tumor suppressor gene in cancer biology -- associated with HGSOC risk (relative risk 1.44, P=1.76x10^-9). This exact variant is already on this site, linked to its basal cell carcinoma page under a different trait context; it is now also linked to this site's ovarian cancer page, a genuine case of the same regulatory variant contributing to risk in two very different cancers through TP53's broad tumor-suppressor role. The study also built a polygenic score from 64,518 variants (trained on FinnGen data, validated in UK Biobank) achieving an odds ratio of 1.46 per standard deviation -- a meaningful improvement in HGSOC risk prediction credited specifically to larger sample size and better genetic imputation, illustrating how methodological progress alone can surface real associations earlier studies missed. This site's ovarian cancer page carried 9 variants before this addition.
Source. Stacey et al. (Nat Commun 2015) conducted a genome-wide association study of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 basal cell carcinoma patients and 266,358 controls. Four new susceptibility loci were reported: 2p24 MYCN (rs57244888[C], OR = 0.76, P = 4.7 × 10⁻¹²), 2q33 CASP8–ALS2CR12 (rs13014235[C], OR = 1.15, P = 1.5 × 10⁻⁹), 8q21 ZFHX4 (rs28727938[G], OR = 0.70, P = 3.5 × 10⁻¹²) and 10p14 GATA3 (rs73635312[A], OR = 0.74, P = 2.4 × 10⁻¹⁶). Fine mapping showed two variants correlated with rs73635312[A] occur in conserved GATA3 binding sites, and expression microarrays and RNA-seq associated rs13014235[C] and the related rs700635[C] with expression of CASP8 splice variants retaining intron 8 sequences.
Positions listed here. rs7538876 (RCC2), rs801114 (RHOU), rs11170164 (KRT5) and rs78378222 (TP53), recorded by the collector from this study. Three of the four index SNPs named above for the new loci have since been collected too -- rs57244888 (MYCN), rs28727938 (ZFHX4) and rs73635312 (GATA3) are now directly on this page, so the odds ratios quoted above for those three loci do belong to variants listed here. Only rs13014235 (CASP8) is still absent.
rs78378222. A common variant in TP53, distinct in kind from the rare high-penetrance TP53 mutations that cause Li–Fraumeni syndrome. Conflating the two would misrepresent both the magnitude and the clinical meaning of this finding.
Clinical use. None. Diagnosis is clinical and dermatoscopic with histological confirmation; treatment is excision or another destructive or topical modality according to subtype, site and size. Prevention is ultraviolet exposure reduction. No genotype is used in screening, diagnosis or management.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Basal Cell Carcinoma comes down to these specific, well-studied positions — not a diagnosis. 146 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 62 of 146 linked studies with a resolved discovery ancestry.
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Basal Cell Carcinoma. MyGeneLog™. https://www.mygenelog.com/conditions/basal-cell-carcinoma
Almost certainly not, and the distinction is important. Li–Fraumeni is caused by rare, high-penetrance TP53 mutations and is diagnosed through clinical genetics on the basis of family history and sequencing. rs78378222 is a common variant in the same gene contributing modestly to a common skin cancer. The gene is the only thing they share.
It very rarely spreads, which is why it is not usually life-threatening. It does grow locally and destroy the tissue it grows into, and it disproportionately occurs on the face — so it is treated, and treated earlier rather than later.
No. Ultraviolet exposure remains the dominant cause and skin type the dominant risk factor. Common variants shift the odds modestly around that; they do not replace it.
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