Have Problems Detoxing? This Gene Can Help (NQO1)

The NQO1 gene encodes an enzyme also named NQO1, which is short for NADPH dehydrogenase quinone 1. The main responsibility of this enzyme is to detox quinones, a family of chemical compounds that can cause oxidative stress [R, R].

Certain genetic variations in NQO1 can reduce the body’s ability to detox, potentially increasing the risk of toxicity and cancer [R, R].

The NQO1 encodes the NQO1 enzyme, which is responsible for detoxing compounds called quinones.

What Are Quinones?

Quinones are a family of naturally occurring compounds that perform a variety of chemical reactions. They can be dangerous in humans because quinones are easily converted into reactive oxygen species, which cause oxidative stress, cellular injury, and DNA damage. These negative effects can lead to the development of cancer [R, R].

Quinones are naturally found in plants, fungi, and bacteria, making diet a major source for humans. Other compounds can also be converted into toxic quinones in the body; these include, importantly, hydrocarbons (also called benzenes), which are found in fuels, cigarettes, cleaning products, and air pollution [R, R, R].

Quinones are chemical compounds that can be converted into reactive oxygen species, which cause cellular and DNA damage. Sources of quinones include diet, smoking, and air pollution.

As mentioned earlier, quinones can harm your body when they are converted into reactive oxygen species. NQO1 prevents this by converting quinones into hydroquinone, much safer compounds that generally does not cause oxidative stress [R].

Other functions of NQO1 include converting ubiquinone (CoQ10) and vitamin E into their antioxidant forms, in which they can help protect against oxidative damage. Also, NQO1 stabilizes p53, a protein that suppresses tumor formation [R].

NQO1 detoxes the body by neutralizing quinones. It also helps form antioxidants in the body and protects proteins that suppress tumors.

Problems can arise when variations in the NQO1 gene reduce the activity and concentration of the NQO1 enzyme. Without sufficient NQO1, more quinone can become reactive oxygen species, which leads to increased cellular and DNA damage [R].

One of the main culprits is a variation called NQO1*2, which affects the SNP rs1800566. This SNP normally has a ‘G’ allele, but in NQO1*2 the allele is an ‘A’ instead. Individuals who are homozygous for the ‘A’ risk allele have little to no NQO1 activity [R, R].

Another major variation is NQO1*3, which is produced by a variation at rs1131341. At this SNP, the normal allele is once again ‘G’ while the risk allele is an ‘A’. This genetic variant leads to a slower conversion of quinone into its safer metabolites [R].

Genetic variations in NQO1 can lead to lower NQO1 activity, which impairs the body’s ability to detox from quinones and leads to increased oxidative damage.

Increased Cancer Risk

Genetic variations of NQO1 can cause increased rates of DNA damage, ultimately developing into cancer if left unchecked. Research has found that NQO1 variants are associated with many types of cancer, including [R]:

• Breast cancer [R]
• Prostate cancer [R]
• Bladder cancer [R]
• Stomach cancer [R]
• Leukemia [R]

Variations in the NQO1 gene are associated with increased rates of many types of cancer, like breast, stomach, and prostate cancer.

Benzene Toxicity

Benzene (hydrocarbons) are chemical compounds found in many fuels, cigarettes, and cleaning products. Exposure is common in urban areas, where vehicles and industrial manufacturing release significant amounts of hydrocarbon air pollution [R, R].

Research shows that people with a NQO1*2 genotype (rs1800566-A) are up to 7.6 times more likely to experience benzene toxicity, even from low-level exposure. The long-term health effects of benzene exposure include anemia, DNA damage, and increased risk of cancer [R, R, R].

NQO1 variants can significantly increase the risk of benzene toxicity, which can cause anemia, DNA damage, and cancer.

Increased Alzheimer’s Risk

There is significant evidence that links oxidative stress to the development of Alzheimer’s disease. As a result, NQO1 genetic variants have been implicated in the development of this disorder [R].

Research has been somewhat mixed, but the majority of studies show that NQO1*2 (rs1800566-A) is much more common in people with Alzheimer’s compared to the healthier ancestral genotype [R].

The NQO1*2 genotype may be associated with Alzheimer’s, but further research is needed. 

Primary SNPs

NQO1 rs1800566

• ‘G’ = Normal detox function
• ‘A’ = Increased risk of toxicity
• About 49% of people have relatively increased risk from a suboptimal genotype (GA or AA)

NQO1 rs1131341

• ‘G’ = Normal detox function
• ‘A’ = Increased risk of toxicity
• About 4% of people have relatively increased risk from a suboptimal genotype (GA or AA)