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.
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.
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.
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)) |
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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