Genes for skin colour and cancer

Human skin comes in many different colours, which, of course, is underpinned by our genetics. But disentangling which genes are involved, and which, if any, of those also help to protect darker skin against cancers like melanoma is an open question. This is particularly interesting when you compare east Asians and Europeans, who are both relatively pale skinned, but affected by skin cancer to significantly different degrees. It’s not straightforward to study though, because genetic “admixture” over the centuries has introduced a whole host of genes that might be responsible. But, speaking with Chris Smith, Penn State’s Khai Ang realised that there might be a way to study this thanks to a community in the Caribbean with strong, relatively pure Native American ancestry who are descended from the east Asian migrants who first populated the Americas thousands of years ago…

Khai -  What are the genes that play a role in the variations of skin colour in the East Asian population? The bigger question that I'm asking is why melanoma is 20 times higher in people of European ancestry versus East Asian people, although we are both considered to have light skin.

Chris -  And how did you try and get at that then?

Khai - One of the key things that is important is to look at the populations around the world. And as we look at human migrations from thousands of years ago, people migrate out of Africa into East Asia and then across the Bering Strait down to the Americas. So I started looking at human migration maps and we identified populations in the Caribbean region and we ended up in Dominica and they have a Native American territory and they are more isolated from the rest of the new world population. So what it means is that they will have a higher Native American ancestry.

Chris -  Why does that matter though? If you can just go and look at people from East Asia and they share a common ancestor with these Native Americans, why do you need a relatively pure or as pure as you can get stock of Native Americans to study?

Khai -  Great questions. So one of the things that are about skin colour is that there are multiple genes affecting skin colour. However, I'm interested in one of the primary genes that's playing a role. So in order for me to look or test the effect of this primary gene, I have to eliminate all other genes. So when I look at the East Asian populations, for example, I cannot use them because there are so many other genes that play a role in the East Asian skin colour. I have to look at human populations that have African ancestry and also East Asian or Native American ancestry. And this is where the Kalinago population from Dominica comes in.

Chris -  How did you then use their DNA in order to work out the answer to your problem?

Khai -  We collected samples from the Native American people and we also measured the skin colour reading of these people. And then we plot that graph looking for people of the lighter skin and also the darker skin. And we extracted DNA from this group of people from the darker skin colour and the lighter skin colour. And after that we sequence them and we look for changes in the DNA that are specific to one group and not to the other group.

Chris -  And have you managed to pinpoint the genes which appear to be doing this accounting for these differences in skin tones?

Khai -  We unfortunately have not identified a specific gene, but we have managed to quantify the effect of Native American ancestry towards the skin colour. So the genetics of Native American ancestry contribute at least 20 melanin units to differences in the skin tone of the Native American populations. Right now we are trying to narrow down genes that are playing a role in these populations.

Chris -  And going back to your starting premise, which is we want to understand why there are differences in risk of melanoma in different populations, how much further does this finding take us along that road?

Khai -  One of the things that we need to do is to be able to identify populations suitable to be used to identify the genes. So we are at least one step closer towards answering the questions of what genes play a role in melanoma. We need to first identify the genes that play a role in skin colour, and then we go down to biochemical pathways. So at least one step closer.