skin & beauty

cancer

AHR

A Detoxification Gene With a Surprising Role in Melanoma (AHR)

Written by Shany Lahan, MS (Neuroscience) on January 12th, 2021

AHR may alter the activity of genes involved in immunosuppression and therapeutic efficacy. How might a variant of AHR promote the progression of melanoma? Find out below.

Summary

AHR codes for a protein that alters the activity of genes involved in detoxification, immunosuppression, and inhibition of targeted therapies. A variant of AHR may play a role in melanoma by increasing the production or activity of AhR. Lifestyle, diet, and supplement modifications may counteract the effects of this variant by limiting or lowering AhR activity.

AHR and Melanoma

The AHR gene codes for aryl hydrocarbon receptor (AhR), a protein that turns genes on or off. UV radiation, synthetic chemicals, air pollutants, and microbe byproducts have all been reported to activate AhR and in turn, alter the activity of protein-coding genes [R, R].

AhR is known to boost the production of detoxification enzymes called CYPs. These enzymes are involved in the breakdown and clearance of foreign substances (xenobiotics), including synthetic chemicals and air pollutants [R].

While this suggests a protective role for AhR in diseases such as cancer, researchers have observed increased levels of AhR in melanoma and other cancer forms [R].

Cancer cells can often avoid detection and consequent death by producing a molecule that immune cells recognize as “normal.” AhR has been suggested to take advantage of this mechanism in order to heighten immune cell evasion [R].

In addition, AhR may lower the efficacy of a targeted melanoma treatment. BRAF is a gene whose mutation (V600E or V600K) promotes melanoma progression, and is present in approximately 50% of patients with melanoma. Medications that block BRAF may improve survival rates in these patients [R].

Studies have shown that AhR may turn on genes that induce resistance to BRAF inhibitors, thereby promoting melanoma progression in those that carry BRAF mutations [R].

A variant of AHR has been associated with melanoma. This variant may increase the production or activity of AhR, resulting in immune evasion, reduced efficacy of targeted therapies, and cancer progression [R, R, R, R].

Your AHR Results for Melanoma

SNP Table

variant	genotype	frequency	risk allele
rs1636744

Primary SNP:

AHR rs1636744 [R, R, R, R]

‘T’ = Higher odds of melanoma
‘C’ = Not associated with melanoma

Recommendations

Lifestyle

Reducing UV Exposure

As UV radiation may exacerbate AhR activity, reducing UV exposure may be beneficial for individuals carrying AHR risk variants [R].

Excessive, unprotected exposure to UV radiation is by far the main risk factor for the development of melanoma. UV from both the sun and artificial sources (tanning beds and sun lamps) damages the DNA of pigment-producing cells (melanocytes), potentially causing mutations that turn these cells into melanomas [R, R, R].

People with low levels of the pigment melanin, who typically have fair skin, blond or red hair, and light-colored eyes, are at higher risk of melanoma than those with dark skin [R].

Alternatively, every single mole has a small probability of turning into cancer. Having a high number of moles, especially if they are large or have atypical features, also increases the risk of this skin cancer type [R, R].

Reducing exposure to UV by limiting sun exposure (especially during the middle of the day), wearing protective clothing and sunscreen, and being aware of skin-sensitizing medications can greatly reduce the risk of melanoma.

Reducing UV exposure may help prevent melanoma by limiting the activation of AhR.

Maintaining a Healthy Weight

Western diets are well-known to promote obesity. These diets also increase LDL-cholesterol and contain high amounts of polycyclic aromatic hydrocarbons (PAHs) — contaminants formed when carbon-based substances are burned (e.g., via grilling or frying). LDL-cholesterol and PAHs have been shown to activate AhR [R, R].

Indeed, one study found that obese children had higher levels of AhR, in comparison to their healthier-weight counterparts [R].

In men, being obese or overweight has been associated with an increased risk of melanoma in 21 studies of almost 25,000 people [R, R, R].

Weight loss may also help improve the effectiveness of chemotherapeutic drugs for melanoma, as seen in a study in mice [R].

Maintaining a healthy weight may help prevent melanoma by limiting the activation of AhR.

Diet

Mediterranean Diet

The Mediterranean diet comprises olive oil, fish, and legumes, as well as flavonoid-rich vegetables and fresh fruit. One flavonoid in particular, luteolin, was shown to suppress AhR in a cell-based study [R].

Adherence to the Mediterranean diet has been associated with a reduction in the risk of melanoma by approximately 30% in multiple studies [R, R, R, R, R].

However, high intake of citrus fruits (a common ingredient of the Mediterranean diet) is linked to an increased risk of melanoma. The high psoralen content of these fruits may make the skin more sensitive to UV radiation [R, R, R, R, R].

The Mediterranean diet may help prevent melanoma by suppressing AhR.

Supplements

B Vitamins

Vitamin B9 (folic acid) and B12 (cobalamin) may block the activity of AhR [R].

Supplementation with a combination of vitamin B6 (pyridoxine), folic acid, and cobalamin was associated with a reduced incidence of melanoma in 3 studies of over 119,000 people [R, R, R].

B vitamins may help prevent melanoma by suppressing AhR.

Shany Lahan

MS (Neuroscience)

Shany received her MSc in Neuroscience from Western University.

Prior to joining SelfDecode, Shany conducted research related to Alzheimer’s disease, and taught science to undergraduate students. She believes that research should be accessible to everyone, regardless of scientific background. Shany joined SelfDecode with a mission to help others optimize their health and wellbeing – as well as help them understand the science behind it all.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

Summary AHR and Melanoma Your AHR Results for Melanoma

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