Odds ratios of 1.06 and 1.09 — small enough that the honest use of this page is to explain what a common cancer variant is, and to point at the two things that actually work: screening on schedule, and knowing whether Lynch syndrome runs in the family.
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.
Colorectal cancer is one of the few common cancers that screening can catch before it becomes cancer at all, by finding and removing the polyps it grows from. That is the single most useful fact about it, and it does not depend on anyone's genome.
An odds ratio of 1.09 means the risk is about nine per cent higher — nine per cent of a number that is itself modest, for one copy of a common variant. Both were found only because tens of thousands of people were compared. That is what a common cancer variant looks like, and this page exists partly to make that concrete.
Lynch syndrome — inherited variants in the mismatch repair genes MLH1, MSH2, MSH6, PMS2 or EPCAM — raises colorectal cancer risk substantially and changes management: colonoscopy far earlier and far more often than the general population, and surveillance for related cancers. Familial adenomatous polyposis, from APC, is rarer and more dramatic still.
Those are found through family history, tumour testing and clinical genetic testing, and they are what a person with several affected relatives should be asking about. Nothing on this page substitutes for that conversation.
Take up screening when it is offered — a stool test or a colonoscopy, depending on where you live. Tell your doctor if a parent, sibling or child has had colorectal cancer, especially young, because that alone can change when your screening should start. And do not sit on blood in the stool, a persistent change in bowel habit, or unexplained weight loss.
None of that is different for someone carrying these variants, which is the point.
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 112 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.
Tian J et al. 2024, Genome medicine rs6117251 (near CASC20), rs73039433 (RHPN2), rs75128197 (EIF3H), rs56270678 (UBE2R2), rs371061408 (LINC01705), rs6507877 (SMAD7), rs11213825 (near POU2AF3), rs28774977 (POU5F1B), rs10318 (GREM1), rs9946510 (SMAD7), rs11604752 (POLD3), rs4583925 (near SLC6A18) and 37 more — PMID:38872215
Fernandez-Rozadilla C et al. 2023, Nature genetics rs117042741 (XRRA1), rs35564340 (near SLC25A28), rs1919364 (GREM1-AS1), rs11108175 (PGAM1P5), rs78341008 (near RNY1P8), rs9983528 (PCNT), rs280097 (near SMARCAD1-DT), rs7810512 (TBRG4), rs2516452 (near HCP5), rs9614460 (SMC1B), rs1554865 (near GREM1), rs966816 (near CASC20) and 20 more — PMID:36539618
Sakaue S et al. 2021, Nature genetics rs12822620 (CCND2-AS1), rs12025420 (LINC02474), rs184201123 (near PPIAP43), rs4871788 (PCAT1), rs57064586 (SLCO2A1), rs8001158 (COL4A2), rs6086195 (near SRSF10P2), rs2427313 (CABLES2), rs1810501 (near RN7SL636P) — PMID:34594039
Harris BHL et al. 2024, Scientific reports rs771590478 (CHST11), rs146812962 (near IZUMO1R), rs80081514 (near GPR83), rs190984989 (PLXNA4), rs184460725 (near GXYLT1), rs532121722 (near LINC01477), rs757853362 (ANKRD19P), rs114717436 (ZCWPW2), rs139372065 (ZCWPW2) — PMID:38538606
Laskar RS et al. 2024, Annals of oncology : official journal of the European Society for Medical Oncology rs2427291 (LAMA5), rs10808556 (CASC8), rs12427378 (DIP2B) — PMID:38408508
Quintanilha JCF et al. 2024, BMC genomics rs2229523 (NT5E), rs11118119 (LINC02869), rs494688 (LINC02535) — PMID:38745123
Wang H et al. 2023, Genome medicine rs138234416 (ZSCAN16-AS1), rs13197175 (near ZKSCAN8P1) — PMID:36869385
Huyghe JR et al. 2019, Nature genetics rs12144319 (TTC22), rs145364999 (CHD1) — PMID:30510241
Ishigaki K et al. 2020, Nature genetics rs9733843 (near RNA5SP299) — PMID:32514122
Law PJ et al. 2019, Nature communications rs61336918 (near LINC01228) — PMID:31089142
Lu Y et al. 2020, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology rs6085662 (near LINC01713) — PMID:31826910
2026-01-29 · A Genome-Wide Association Study of Colorectal Cancer Mortality Outcomes Among Individuals of African and Admixture Ancestry. Molecular Carcinogenesis. 2026. DOI:10.1002/mc.70086
African Americans have the highest colorectal cancer (CRC) mortality rate in the US, but essentially no prior GWAS had looked specifically at genetic contributors to CRC survival outcomes in this population -- as opposed to who gets CRC in the first place. This study followed 500 Black-identifying participants with incident CRC from the Southern Community Cohort Study (2002-2009), tracking 316 total deaths and 184 CRC-specific deaths via cancer registries and the National Death Index. It found two variants in near-perfect linkage disequilibrium within LTBP1 -- rs34071846 and rs12712337 -- associated with more than doubled CRC-specific mortality risk (hazard ratio 2.74, P=3.78x10^-8), plus a noncoding RNA variant, rs10103953, associated with lower CRC-specific mortality (HR=0.52) and a variant in MCTP2, rs7171579, associated with lower overall mortality (HR=0.59, P=2.13x10^-8). This is specifically a prognostic/survival finding, not a risk-of-developing-CRC finding, and directly addresses a documented health disparity with genetic evidence rather than assumption. This site's colorectal cancer page carries 125 variants; LTBP1 and MCTP2 are not currently among them.
rs6687758 (1q41). Identified in a meta-analysis of three UK GWAS (3,334 cases, 4,628 controls) with validation in 18,095 cases and 20,197 controls; OR 1.09, P = 2.27 x 10-9. The same analysis reported rs6691170 at the same locus (OR 1.06, P = 9.55 x 10-10) and new loci at 3q26.2, 12q13.13 and 20q13.33, and noted explicitly that further variants of similar effect size remained to be found.
rs4444235 (14q22.2, BMP4). From a meta-analysis of two GWAS comprising 13,315 individuals genotyped for 38,710 tagging SNPs, with replication in up to eight independent series totalling 27,418 subjects; P = 8.1 x 10-10. The same study reported 16q22.1 (CDH1), 19q13.1 (RHPN2) and 20p12.3. BMP4 is part of the bone morphogenetic protein signalling pathway, which is also disrupted in juvenile polyposis syndrome — a rare monogenic polyposis condition — making it a plausible biological candidate rather than an anonymous statistical hit.
Monogenic contrast. Lynch syndrome (germline MLH1, MSH2, MSH6, PMS2 or EPCAM) and familial adenomatous polyposis (APC) carry substantially elevated risk and drive intensive surveillance protocols. Universal mismatch-repair or microsatellite-instability testing of colorectal tumours is standard practice in many systems and is how Lynch syndrome is most often identified. Common variants such as those here have no role in that pathway and no role in screening eligibility, which is set by age, family history and previous findings.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Colorectal Cancer comes down to these specific, well-studied positions — not a diagnosis. 238 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 130 of 238 linked studies with a resolved discovery ancestry.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| DPYD | Fluoropyrimidines (fluorouracil, capecitabine) | The clearest argument on this site for testing before a first dose rather than after a bad reaction. Fluorouracil and capecitabine are the backbone of colorectal cancer chemotherapy, and one enzyme — dihydropyrimidine dehydrogenase — clears most of what is given. People carrying no-function DPYD alleles clear very little, and standard doses have caused severe and fatal toxicity. CPIC publishes dose recommendations by genotype, and pre-treatment DPYD testing is now recommended before fluoropyrimidine treatment in several health systems. Nothing here is a reason to refuse chemotherapy; it is a reason for the test to happen before it starts. (CPIC Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update, Clinical Pharmacology & Therapeutics (PMID 29152729)) |
| CYP2D6 | Ondansetron and tropisetron | These are the anti-sickness drugs given alongside chemotherapy, and here the genotype that causes trouble is the fast one rather than the slow one. CYP2D6 ultrarapid metabolisers clear ondansetron and tropisetron quickly enough that the dose may not control the nausea, and CPIC recommends choosing an antiemetic that CYP2D6 does not clear — granisetron, for instance. No recommendation is made for poor metabolisers, because slower clearance of these drugs has not been shown to cause harm. It is a small point with a disproportionate effect on whether somebody can tolerate a course of treatment at all. (CPIC Guideline for CYP2D6 and Ondansetron and Tropisetron (Clin Pharmacol Ther 2017, PMID 28002639).) |
| UGT1A1 | Irinotecan | Irinotecan is a mainstay of colorectal cancer treatment, and the enzyme that disposes of its active metabolite is the same one behind Gilbert syndrome — a harmless inherited cause of mildly raised bilirubin that perhaps one person in ten carries in the double dose. Those people clear the active metabolite slowly and are at higher risk of severe neutropenia and diarrhoea, which is why the US prescribing information warns about UGT1A1*28 homozygotes and a reduced starting dose is commonly used. This is not a CPIC guideline: CPIC rates the pair level A on the strength of the evidence, but the guidance in use comes from the drug label and from the Dutch pharmacogenetics working group. Testing before the first cycle is routine in some centres and not in others. (US prescribing information for irinotecan (CAMPTOSAR); Dutch Pharmacogenetics Working Group recommendation for UGT1A1 and irinotecan. CPIC lists the pair at level A but has not published a guideline for it.) |
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Colorectal Cancer. MyGeneLog™. https://www.mygenelog.com/conditions/colorectal-cancer
Roughly nine per cent higher odds than someone without that copy — of a risk that is already modest. It is a real association measured in tens of thousands of people, and it is far too small to act on individually.
No. Screening schedules are set by age, family history and previous findings. If a close relative had colorectal cancer, particularly young, that is worth raising with your doctor — it can genuinely change when you should start.
It is suspected from patterns — colorectal or endometrial cancer at young ages, several affected relatives, or certain tumour test results — and confirmed by clinical genetic testing. It is a different question from anything on this page and a much more consequential one.
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