NQO1 Gene: Metabolism of quinones, benzene, and more

Your genes code for the enzymes that break down the toxic substances we all encounter each day. The ability to clear out potential carcinogens is important when it comes to preventing cancer.

This article covers the function of the NQO1 enzyme and explains how these genetic variants impact your risk for certain cancers.

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NQO1 gene:

The NQO1 gene codes for an enzyme that breaks down quinones, benzene, and some specific chemotherapy drugs.

If you think back to high school chemistry, you may remember redox reactions – where the reactants either lost or gained an electron.

NQO1 is acting as a reducing agent, which is important in the body’s ability to make certain substances easier to eliminate.

Quinones and hydroquinones:

The NQO1  gene codes for the enzyme NAD(P)H: quinone oxidoreductase 1 enzyme. This enzyme uses NADH or NADPH to reduce quinones to hydroquinones.

Quinones are usually formed in the body as intermediates – the product that occurs when the body is breaking down certain substances. These types of reactions go on all the time in the body. Because quinones are so reactive, it is important for the body to convert quinones into hydroquinones quickly.

For example, when the body breaks down estrogen for elimination, an intermediate is formed which is an estrogen quinone metabolite linked to breast cancer risk. NQO1 can help to metabolize and get rid of estrogen quinone metabolites, thus decreasing cancer risk.

Related article: Estrogen metabolism genes

NQO1 is also involved in cellular defense against oxidative stress, as well as the conversion of CoQ10 and the conversion of vitamin K. In the reduction (chemistry meaning, think redox reaction) of Vitamin K, NQO1 is mostly involved in turning vitamin K3 into the active form for blood clotting and bone-building[ref].

NQO1 is also involved in breaking down outside toxins such as benzene and some chemotherapy drugs. Benzene is a carcinogen found in gasoline fumes, laundry detergent, furniture wax, industrial uses, pesticides, and smoke. Benzene is also a component of smog.[ref][ref]

Additionally, NQO1 is important in the process that a cell goes through to divide and create a new cell. NQO1 has been shown to interact with NAD+ and SIRT2 during cell division.[ref]

Related article: NAD+, NR, NMN and genetics

Animal studies show that a non-functioning NQO1 gene leads to gut impermeability and inflammation (leaky gut)[ref].


NQO1 Genotype Report

Research shows there are two common NQO1 variants that reduce function and increase the risk for certain cancers. The variant NQO1*2 (P187S) leads to a deficiency in the enzyme, while the NQO1*3 (R139W) variant has reduced enzyme activity, which may be dependent on the substance.

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Check your genetic data for rs1800566 (23andMe v4, v5; AncestryDNA):

  • A/A:  NQO1 *2 – non-functioning NQO1, higher risk of cancer from benzene[ref] increased risk of lung cancer in smokers[ref] increased risk of Parkinson’s from pesticide exposure[ref], increased risk of cataracts for outdoor workers[ref]
  • A/G: intermediate enzyme function, higher risk of cancer from benzene, increased risk of Parkinson’s from pesticide exposure, increased risk of cataracts
  • G/G: typical function

Members: Your genotype for rs1800566 is .

Check your genetic data for rs1131341 (23andMe v4 only):

  • A/A: slightly decreased enzyme function, NQO1*3[ref][ref]
  • A/G: decreased NQO1 function
  • G/G: typical

Members: Your genotype for rs1131341 is .

 


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Related Articles and Topics:

Phase I and Phase II detoxification
Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.

Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.

How your genes influence BPA detoxification:
BPA, a chemical found in some plastics, has been linked to a variety of effects on people including obesity, insulin resistance, and epigenetic effects on the fetus. Genetics plays a role in how quickly you can eliminate BPA from your body.


References:

Fong, Chin-Shih, et al. “Pesticide Exposure on Southwestern Taiwanese with MnSOD and NQO1 Polymorphisms Is Associated with Increased Risk of Parkinson’s Disease.” Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 378, no. 1–2, Mar. 2007, pp. 136–41. PubMed, doi:10.1016/j.cca.2006.11.006.

Gong, Xing, et al. “Quinone Oxidoreductases and Vitamin K Metabolism.” Vitamins and Hormones, vol. 78, 2008, pp. 85–101. PubMed, doi:10.1016/S0083-6729(07)00005-2.
Hsieh, Tze-chen, et al. “Induction of Quinone Reductase NQO1 by Resveratrol in Human K562 Cells Involves the Antioxidant Response Element ARE and Is Accompanied by Nuclear Translocation of Transcription Factor Nrf2.” Medicinal Chemistry (Shariqah (United Arab Emirates)), vol. 2, no. 3, May 2006, pp. 275–85.

Medina-Carmona, Encarnación, et al. “Conformational Dynamics Is Key to Understanding Loss-of-Function of NQO1 Cancer-Associated Polymorphisms and Its Correction by Pharmacological Ligands.” Scientific Reports, vol. 6, Feb. 2016. PubMed Central, doi:10.1038/srep20331.

Megarity, Clare F., and David J. Timson. “Cancer-Associated Variants of Human NQO1: Impacts on Inhibitor Binding and Cooperativity.” Bioscience Reports, vol. 39, no. 9, Sept. 2019. PubMed Central, doi:10.1042/BSR20191874.

Moran, Julie L., et al. “A Potential Mechanism Underlying the Increased Susceptibility of Individuals with a Polymorphism in NAD(P)H:Quinone Oxidoreductase 1 (NQO1) to Benzene Toxicity.” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 14, July 1999, pp. 8150–55.

Nam, Seung Taek, et al. “Role of NADH: Quinone Oxidoreductase-1 in the Tight Junctions of Colonic Epithelial Cells.” BMB Reports, vol. 47, no. 9, Sept. 2014, pp. 494–99. PubMed Central, doi:10.5483/BMBRep.2014.47.9.196.

Office of Dietary Supplements – Riboflavin. https://ods.od.nih.gov/factsheets/Riboflavin-Consumer/. Accessed 25 Sept. 2019.
Pey, Angel L., et al. “FAD Binding Overcomes Defects in Activity and Stability Displayed by Cancer-Associated Variants of Human NQO1.” Biochimica Et Biophysica Acta, vol. 1842, no. 11, Nov. 2014, pp. 2163–73. PubMed, doi:10.1016/j.bbadis.2014.08.011.

Ross, David, et al. “Benzene Toxicity: The Role of the Susceptibility Factor NQO1 in Bone Marrow Endothelial Cell Signaling and Function.” Chemico-Biological Interactions, vol. 192, no. 1–2, June 2011, pp. 145–49. PubMed Central, doi:10.1016/j.cbi.2010.10.008.
Siegel, David, et al. “Redox Modulation of NQO1.” PLoS ONE, vol. 13, no. 1, Jan. 2018. PubMed Central, doi:10.1371/journal.pone.0190717.

Tan, Xiang-Lin, et al. “Candidate Dietary Phytochemicals Modulate Expression of Phase II Enzymes GSTP1 and NQO1 in Human Lung Cells.” The Journal of Nutrition, vol. 140, no. 8, Aug. 2010, pp. 1404–10. PubMed Central, doi:10.3945/jn.110.121905.

US EPA, OAR. “Smog, Soot, and Other Air Pollution from Transportation.” US EPA, 10 Sept. 2015, https://www.epa.gov/transportation-air-pollution-and-climate-change/smog-soot-and-local-air-pollution.

Yamamoto, Yuzo, et al. “Biological Interaction of Cigarette Smoking on the Association between Genetic Polymorphisms Involved in Inflammation and the Risk of Lung Cancer: A Case-Control Study in Japan.” Oncology Letters, vol. 13, no. 5, May 2017, pp. 3873–81. PubMed, doi:10.3892/ol.2017.5867.

Zarei, Narjes, et al. “The Relationship between NQO1 C609T and CAT C-262Tgenetic Polymorphisms and the Risk of Age-Related Cataracts.” Molecular Biology Research Communications, vol. 4, no. 3, Sept. 2015, pp. 143–49.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.