Ireland and the Irish people are associated with many things, including leprechauns, green shamrocks, Celtic harps, herds of sheep grazing the countryside, and Saint Patrick’s Day. On March 17, the globe celebrates the patron Apostle of Ireland with parades and religious feasts in honor of the date of Patrick’s approximate death – March 17, 493 (the actual year is debated by historians and may be closer to 460).

The Irish are also associated with red hair and light skin—for good reason: approximately 10% of Irish people have red hair, light skin, and light-colored eyes. This article explores the intriguing medical genetics behind these characteristics. We will delve into the genetic factors that give many Irish their distinctive red hair and light skin, and how these traits relate to human genetics, particularly melanoma.

Why do people have red hair?

Red hair appears most prominently in Ireland and Scotland. In fact, approximately 10% of the population in Ireland has red hair, which is the highest concentration in the world. It is also naturally occurring among ancestral descendants in England, Denmark, Iceland and along the Norwegian coast. Natural redheads residing in the U.S. are presumed to have Northwestern European ancestry.

Within DNA, there are pieces to specify that an individual will have red hair. These pieces are collectively called “Red Hair Color” or RHC variants. These variants are responsible for the production of pigment that will determine hair, skin, and dark or light eye color.

The main DNA piece responsible for red hair color, and a part of the RHC variants, is abbreviated MC1R, which stands for the melanocortin 1 receptor. There are hundreds of variants of the MC1R, but it’s particularly important because it regulates the production of pigment.

When the MC1R is fully functional, it produces brown-black pigments inside melanocyte cells. These dark brown-black (melanin) pigments produced by MC1R are called eumelanin. They will be secreted. Humans with dark colored skin, such as those of African descent, have fully functional MC1R that secretes eumelanin.

When the MC1R is mutated, it loses some of its function, and instead of producing dark pigments, it makes red-yellow pigments. These lighter-colored pigments produced inside melanocyte cells are called pheomelanin and will be secreted. If a person has natural red hair, their melanocyte cells produce predominantly pheomelanin, not eumelanin.

Scientists call the MC1R mutated Red Hair Color variants R151C, R160W, and D294H.¹ If a person has natural red hair, s/he inherited R151C, R160W, or D294H, the mutated forms of MC1R. Their cells produce a red-yellow pigment from the mutated MC1R.

Although this genetic mutation makes the MC1R not fully functional, its inheritance was genetically tolerated among Northwestern European populations. This means that at Northern latitudes, selective pressure did not eliminate it from the population because having mutated MC1R would not reduce one’s survival up North.²  The opposite could occur closer to the equator where mutations in the MC1R causing red-yellow pigment production are not found. The graphic below visually describes the inheritance of MC1R variants at different latitudes.

Why do those with red hair also have light skin and eyes?

In addition to producing light-colored, red-yellow pigments responsible for red hair, the Red Hair Color MC1R variants are also responsible for light skin color.

Melanocytes give skin its color—no matter what color your skin is. Melanocytes produce and secrete melanosomes—pod-like vesicles—that contain either pheomelanin or eumelanin pigments. Skin cells absorb these melanosomes, which give skin its color. The darker your skin is, the more eumelanin your melanocytes have produced. The lighter your skin, the less eumelanin your melanocytes have produced. And if you have natural red hair, you will also have very light skin, because your melanocytes have produced pheomelanin instead of eumelanin.

Although eye color is far more complicated, a similar process contributes to dark eye color. Eumelanin allows the eyes to have a dark brown-black hue. Without a fully functioning MC1R, eumelanin pigment cannot be produced in the eyes, and without eumelanin, the eyes cannot be dark.

Those with natural red hair have a mutated MC1R, which gives them their red hair color, light skin color, and light eye color.

Are those with red hair at risk for melanoma?

The answer is a definite YES. Those with natural red hair, light eyes, and light skin inherit an increased genetic risk for melanoma development. Studies have established the connection between melanoma and Red Hair Color variants of MC1R: R151C, R160W, and D294H.³

The risk does not mean all people with natural red hair color are destined for melanoma. It means they are more likely than those with darker pigmentation to sustain cellular damage that might lead to cancer later in life. It’s important to note that increased risk isn’t a guarantee.

A lot depends on lifestyle choices and other factors.  For example, if a red- haired person sustains blistering sunburns as a child or has routine exposure to UV, possibly through indoor tanning or through travel to lower latitudes, it would have an enormous impact.  Lack of sunscreen use or UV-protective clothing when outdoors would also have an impact.   Having greater than 50 moles is also a risk factor.

Additionally, whether a red-haired person has first-degree relatives with melanoma is a major factor, too. A family history would indicate whether additional genetic risk factors are present, increasing the risk. The bottom line is that the same melanoma risk factors for all people are risk factors for those with red hair; these risk factors are simply more risky for those with mutated MC1R.

Why does lacking eumelanin increase the risk of melanoma?

Eumelanin, the dark pigment, helps protect skin cells from the damaging effects of UV. Individuals with Red Hair Color variants do not have abundant eumelanin. Therefore, when their skin cells are exposed to UV, they have zero natural protection against it, while those with dark pigments have some.

Unfortunately, it’s more complicated than just UV. Scientific studies have demonstrated that pheomelanin itself can damage DNA.⁴  Similarly, in addition to regulating pigment production, the MC1R regulates the repair of DNA damage and helps preserve the integrity of the genome, which are major determinants of cancer risk.³ In other words, functional (unmutated) MC1R protects our chromosomes–the critical material we inherited from our moms and dads that makes us who we are—and those with mutated MC1R do not have that protection.

Among individuals who have developed melanoma and have Red Hair Color variants, the tumors have significantly more DNA mutations compared to others.⁵ These mutations are acquired during a red-haired person’s lifetime. Because many melanomas occur later in life, past the reproductive years, Red Hair Color variants of MC1R like R151C, R160W, and D294H are passed to the offspring. This allows mutated MC1R to continue to exist in the human genome, especially at Northern latitudes.

What is predicted for future populations and MC1R genetics?

Fully functional MC1R and related genetics are observed in populations linked to Africa. Protection from intense UV rays is essential along the equator, where the sun is parallel to the Earth. The production of dark pigments to help protect the skin is necessary for healthy living at that latitude. It explains why mutations in MC1R that make it not function are very rarely, if ever, observed in native African populations.

In addition to MC1R mutations occurring in Northern European populations, populations throughout Asia have different MC1R genetics compared to the rest of the globe. There are at least 200 MC1R variants, meaning that most of these are different from the Red Hair Color mutated variants from Ireland, are observed in Eastern and Southeastern Asians.¹ The MC1R genetics here represent those among the largest populations in the world.

The ratio of the pigments eumelanin and pheomelanin determines an individual’s skin color. Therefore, hundreds of variations in MC1R exist worldwide. These pigment variations provided skin protection through the natural selection of our ancestors’ genetics, especially before the 1500s, when people started moving around the globe.

Nowadays, the variations we see among hair and skin colors are largely a reflection of global migration and genetic mixing that began after 1500. With the same mixing, estimates suggest within the next 10,000 years, humankind will have only one race with the same hair, eye, and skin color with minimal variations. It’s predicted that mutated MC1R will not be represented.

Conclusion

If you have natural red hair, you carry a mutation in the MC1R gene, which is also associated with fair skin and light-colored eyes. This combination significantly increases your risk of developing melanoma. Start by taking proactive steps to safeguard your skin this March and beyond.

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References

1. Upadhyay PR, Swope VB, Starner RJ et al. Journey through the spectacular landscape of melanocortin 1 receptor. Pigment Cell Melanoma Res. 2024;37(5):667-680. doi: 10.1111/pcmr.13180.

2. Guida S, Guida G, Goding CR. MC1R Functions, Expression, and Implications for Targeted Therapy. J Invest Dermatol. 2022;142(2):293-302.e1. doi: 10.1016/j.jid.2021.06.018.

3. Guida S, Bartolomeo N, Zanna PT et al. Sporadic melanoma in South-Eastern Italy: the impact of melanocortin 1 receptor (MC1R) polymorphism analysis in low-risk people and report of three novel variants. Arch Dermatol Res. 2015; 307:495-503.

4. Mitra D, Luo X, Morgan A et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature. 2012; 491:449-4532012.

5. Johansson PA, Pritchard AL, Patch AM et al. Mutation load in melanoma is affected by MC1R genotype. Pigment Cell Melanoma Res. 2017; 30:255-258.