Colorectal cancer risk (8q24)

A variant in the 8q24 'gene desert' that helps regulate the MYC gene is one of the most replicated common signals for colorectal cancer (and is also linked to prostate cancer). Each copy nudges risk modestly; screening and lifestyle matter far more.

What this 8q24 variant does

This variant sits in a gene desert on chromosome 8q24, in a stretch of DNA with no protein-coding gene for hundreds of kilobases. It works as an enhancer, a switch that loops through three-dimensional space to reach MYC, one of the most important growth-regulating genes in the genome, and the risk version binds a transcription factor slightly differently.

That is why the same small region turns up repeatedly in cancer genetics: it nudges the activity of a growth gene in the tissues where the enhancer is active.

It is a colorectal variant and a prostate variant

This page frames the variant around colorectal cancer, and that association is real, but the largest catalogued signal for it is prostate cancer, from a study of 122,188 cases and 604,640 controls of European ancestry plus substantial African-ancestry samples, with an odds ratio of about 1.23 per copy and 35 supporting publications in this site's evidence file.

Reporting one trait per variant is a simplification the format forces. If you carry risk copies here, the honest summary is a small increase in the odds of both colorectal and prostate cancer rather than one of them.

How to read a result here

An odds ratio near 1.2 per copy is modest, and both alleles are common, close to evenly balanced in European-ancestry reference samples, so a large share of people carry risk copies. This is background variation rather than a finding that singles you out.

Screening decisions are made on age, family history and national guidelines. Colorectal screening from around age 45 to 50, and earlier with a family history, does far more for colorectal risk than any common variant, because it removes precancerous polyps rather than predicting them.

What this variant does not tell you

Lynch syndrome and familial adenomatous polyposis, the inherited colorectal cancer syndromes, are caused by rare damaging variants in mismatch repair genes and APC. They carry lifetime risks in a completely different range, they change screening schedules substantially, and they are not read here or by a consumer genotyping chip.

Several relatives with colorectal, endometrial or related cancers, or a diagnosis before 50, is the pattern that should prompt a conversation about clinical genetic testing, whatever a common variant shows.

What each rs6983267 genotype means

rs6983267 has three possible genotypes: TT, GT and GG.

Lower 8q24 cancer-risk variant (rs6983267 TT). You don't carry the 8q24 colorectal-cancer variant, so as far as this common cancer-risk marker shows, your risk is on the lower side. Recommended screening (such as colonoscopy at the usual age) and a healthy lifestyle matter far more than this one marker.

Slightly higher colorectal risk (rs6983267 GT). You carry one copy of the 8q24 variant linked to colorectal (and prostate) cancer. It nudges risk up modestly and is only one of many factors, so following normal screening guidance and a healthy lifestyle is the practical takeaway.

Higher colorectal risk (rs6983267 GG). You have two copies of the 8q24 cancer-risk variant, which raises your statistical risk a bit more (the per-copy effect is still modest). Most people with this genotype never develop cancer, so keeping up with recommended screening is the main and very effective action.

Evidence & sources

Across global populations, about 41% of people carry two copies of this variant, and about 18% carry none.

This variant appears in 35 published genetic studies: PubMed 17401363 · PubMed 17618284 · PubMed 18264096 · PubMed 18264097 · PubMed 18372905 · PubMed 21242260 · PubMed 21743057 · PubMed 23266556 · PubMed 24740154 · PubMed 24753544 · PubMed 24836286 · PubMed 25939597 · PubMed 26034056 · PubMed 26151821 · PubMed 26965516 · PubMed 28960316 · PubMed 29471430 · PubMed 29917119 · PubMed 30104761 · PubMed 30510241 · PubMed 30529582 · PubMed 31089142 · PubMed 31562322 · PubMed 31826910 · PubMed 33293427 · PubMed 33398198 · PubMed 34290314 · PubMed 34594039 · PubMed 36539618 · PubMed 37340002 · PubMed 37945903 · PubMed 37965154 · PubMed 38538606 · PubMed 38872215 · PubMed 39024449.

Common questions

Does this variant mean I will get colorectal cancer? No. The effects catalogued at this locus are around 1.2 times the odds per copy, on alleles that are common in every population. Age, family history, smoking, alcohol and body weight matter more, and screening matters most of all because it removes polyps before they become cancer.

Why is the same variant linked to prostate cancer? Because it acts as a long-range enhancer of MYC, a growth-regulating gene, and the enhancer is active in more than one tissue. The 8q24 region is one of the best-known examples of a single locus contributing to several cancers.

Related

Age-related macular degeneration risk · Atrial fibrillation risk (4q25) · Breast cancer (female) · Coronary artery disease risk (9p21) · Factor V Leiden thrombophilia · Rheumatoid arthritis · Venous thromboembolism (clots)