NQO1 Genotype

This test tells you whether you inherited a weaker version of the NQO1 gene. That gene makes an enzyme your cells use to disarm certain reactive chemicals. People with two copies of the common variant keep only 2% to 4% of normal enzyme activity. That isn't a disease, but it changes how your body handles some exposures you control.

The clearest findings are about context. In smokers, the variant has been tied to more colorectal polyps, and in workers exposed to benzene, to benzene poisoning. This is still a research marker with no guideline behind it, so treat your result as a reason to take certain exposures and screenings more seriously, not as a forecast.

What the Enzyme Does

NQO1 is a detox enzyme that works inside your cells. It handles quinones, a family of reactive chemicals, and turns them into less reactive forms in one chemical step. Done that way, they are less likely to cycle through unstable byproducts that can damage DNA and proteins.

When cells face chemical stress, a defense switch called Nrf2 turns this gene up. Researchers often measure NQO1 activity as one sign that this defense system is active. That is a different question from your inherited genotype.

The enzyme is made in many tissues, including the liver, the lining of the colon, breast tissue, and immune cells. It also activates some cancer drugs, which matters later in treatment settings.

Reading Your Genotype

The common variant swaps one DNA letter at position 609 of the gene. Labs report the same change under several labels: C609T, rs1800566, Pro187Ser, or NQO1*2. The altered enzyme gets flagged by the cell's protein disposal system and broken down quickly, so less of it is around to work.

• CC (two typical copies): you make full amounts of working enzyme.
• CT (one copy of the variant): you make a reduced amount.
• TT (two copies): you keep only 2% to 4% of normal activity, close to having none.

How common this is depends heavily on ancestry. The variant makes up roughly 19% of gene copies in people of European ancestry and about 43% in people of Asian ancestry. So a TT result is uncommon in some families and routine in others, and that shapes how studies in one population apply to you.

Esophagus, Stomach, and Colon

The digestive tract is where the variant's cancer links are more consistent. A large pooled analysis found it raised risk across gastrointestinal cancers, though modestly, with the size of the effect varying by ancestry and by which organ was studied. The individual studies below show where the signal was strongest.

Sources: Zhang et al., Carcinogenesis 2003; Zhang et al., World Journal of Gastroenterology 2003; Tijhuis et al., International Journal of Cancer 2007.

The colon findings go further. In one study of about 540 people, the risk tied to the variant was highest for colorectal tumors carrying a K-ras codon 12 mutation, with roughly ten times the odds. A Polish study found the TT genotype raised colorectal cancer risk, and a 2014 meta-analysis found a colorectal cancer signal in both Asian and Caucasian populations, especially in smokers.

Not every study agrees. A study in north India found no link between the variant and esophageal cancer risk or survival. The pattern that holds up is a real but moderate effect whose size depends on ancestry and exposure.

If you carry the variant and smoke, or have a family history of digestive cancer, you have two reasons to start colorectal screening on time and not let it slide. Smoking is the exposure you can remove, and the polyp finding suggests it's the one that matters most for carriers.

Lung Cancer and the Split Evidence

Lung cancer is where this gene gets confusing. In one study of 1,937 people, there was no overall link, but in former and current smokers the relationship changed with how much and how long people had smoked.

Other work points the opposite way or nowhere. A review concluded the variant was linked to lower lung cancer risk. In Japan, the typical CC genotype was the one tied to lung cancer. A 2012 meta-analysis found no overall association, though some subgroups by ancestry and cancer type showed signals. A later meta-analysis again found no overall association.

Both can be true because this enzyme disarms some chemicals and switches others on, including certain cancer drugs. Whether having less of it helps or hurts depends on which chemicals you're exposed to, how much, and your ancestry. So NQO1 isn't a good gene or a bad gene. It's a modifier of exposures, and your smoking history tells you more about your lung risk than this result does.

Blood Cancers and Benzene

The oldest and most cited finding involves benzene, a solvent found in fuels and some industrial settings. Among exposed workers, benzene poisoning was linked to the 609T variant, and benzene poisoning itself raises the risk of leukemia and related bone marrow disorders. A second study of about 300 workers found the same gene, alongside smoking and alcohol, contributed to poisoning risk.

For leukemia in general the picture is mixed. Pooled analyses tie the variant to higher risk of acute myeloid leukemia, especially in Asian populations and adults, and to acute lymphoblastic leukemia in non-Asian populations and adults. Childhood data are less consistent: several case-control studies found no link, while a family study and later meta-analysis found signals in some models.

If your work involves fuels, solvents, or chemical plants, a variant result is a concrete reason to take exposure controls seriously. This is the setting where the gene's effect is best documented.

Bladder, Breast, and Skin Cancer

A broad meta-analysis found the variant's strongest site-level cancer association was with bladder cancer. Breast cancer links showed up in two separate European populations, and in a study of Chinese women, the variant changed how oral contraceptive use related to breast cancer risk.

Skin cancer is the other standout. Among people with basal cell carcinoma, the most common skin cancer, having the null genotype was the strongest predictor of developing more tumors, at roughly three times the rate. If you carry the variant and have had one basal cell cancer, regular skin checks are worth keeping up.

Blood Pressure and Metabolism

The newest finding is outside cancer entirely. In an 8-year study of 509 Kurdish adults in Iran, people with homozygous high-risk NQO1 or Nrf2 genotypes developed high blood pressure at about 2.8 times the rate. The type 2 diabetes signal was strongest when an Nrf2 variant and one NQO1 variant copy appeared together, so it shouldn't be read as an NQO1-only finding.

Oxidative stress means a buildup of reactive chemicals that can injure cells. The researchers traced the blood pressure and diabetes links to oxidative stress, inflammation, fatty liver, and abnormal blood fats.

This is one population and one study, so it's a lead rather than a settled fact. Still, blood pressure is cheap to track and easy to act on, which makes it a sensible thing to watch if you carry the variant.

How Some Medicines Behave

Because NQO1 activates certain drugs, your genotype can affect whether they work. The clearest case is idebenone, a treatment for Leber hereditary optic neuropathy, an inherited condition that damages the optic nerve. People with two nonworking NQO1 copies had the poorest response, because the drug depends partly on this enzyme to do its job.

Other findings come from people already being treated for cancer. After surgery for stage II and IIIa lung cancer, people with two variant copies had worse overall survival. Among about 200 people receiving a donor stem cell transplant, variant carriers had more treatment-related deaths, and in Bangladeshi women with breast cancer the gene helped predict chemotherapy response and side effects.

If you're ever facing idebenone, a donor stem cell transplant, or chemotherapy, bring this result to the treating team. It won't decide the plan, but it's information they may not otherwise have.

Your Genes Versus Your Tumor

Much of the NQO1 literature measures something this test does not: how much NQO1 protein a tumor makes. That depends on the tumor's own changes and gene control inside the tumor, not just on what you inherited.

Tumor-level findings do not all point the same way. In breast cancer, one study linked high tumor levels to a poorer outlook, while another large study did not find it useful as a prognostic marker. Ovarian cancer reviews also focus on tumor NQO1 levels, not inherited genotype. In pancreatic cancer treated with gemcitabine plus capecitabine, high tumor levels predicted better survival, while inherited genotype alone added nothing to the prediction.

Tumor sequencing is also a separate test. In a study of 47 people with advanced esophageal cancer, NQO1 was among the genes often mutated in the tumor, and treatment chosen from that sequencing was tied to lower risk of death. That's evidence about sequencing cancer tissue to pick drugs. It says nothing about your inherited genotype.

A Result You Only Need Once

Your NQO1 genotype was set at conception and won't change. There's nothing to retest and no trend to follow. The value comes from folding the result into decisions you make for years: about smoking, workplace exposures, cancer screening, and certain treatments.

What does deserve ongoing tracking is downstream. If you carry the variant, check your blood pressure at least yearly, keep colorectal screening on schedule, and get regular skin checks if you've had a basal cell cancer. If you smoke, a cotinine test can confirm whether you've truly stopped, including secondhand exposure.

When a Result Can Mislead

• Variant coverage: a negative result only rules out the variants the lab checked. A single-letter test can miss rare NQO1 changes; sequencing sees more but may report uncertain variants.
• Ancestry changes the meaning: the variant is far more common in people of Asian ancestry, and some findings held in one population but not another, so match the evidence to your own background.
• Tumor versus inherited DNA: a report from cancer tissue sequencing can show NQO1 changes you didn't inherit, and those don't apply to your relatives or your baseline risk.
• Consumer DNA reports: services that read single DNA letters may report rs1800566 correctly but miss other variants. Clinical-grade sequencing adds quality checks and clearer reporting.
• Sample quality: blood, saliva, and cheek swabs should give the same inherited genotype, but a poor sample can fail or need recollection.

What to Do With a Variant Result

A CC result for the common variant means this enzyme is expected to work normally. A CT or TT result doesn't call for alarm, but it does sharpen priorities. The stronger the exposure in your life, the more the result matters.

• If you smoke: quitting is the highest-yield step tied to this result, given the polyp and lung findings in smokers.
• If you work with fuels or solvents: take exposure controls seriously, and consider a complete blood count to spot early bone marrow effects.
• If digestive cancer runs in your family: keep colorectal screening on schedule, and discuss earlier or more frequent screening with a gastroenterologist.
• If you're facing idebenone, chemotherapy, or a donor stem cell transplant: share the result with the treating team before treatment starts.

A genetic counselor is worth a visit if you have a strong family cancer history. That history is often better explained by other genes, which a broader hereditary cancer panel can check. NQO1 alone won't explain why several relatives developed cancer.