East Asian genes may solve the skin cancer puzzle

January 7, 2014 by Khai C. Ang, The Conversation
Skin colour doesn’t just affect your tanning ability. Credit: PA

Europeans fall prey to skin cancer because of their lighter skin, while Africans' dark skin protects them. But East Asians, whose skin colour resembles that of Europeans, are similar to Africans in their low susceptibility to melanoma – the deadliest skin cancer. No one yet knows why, but our research might hold the answer and perhaps help find treatment for the cancer.

In 2005, Keith Cheng at Pennsylvania State University stumbled upon the genetic mutation responsible for light in Europeans. This was an accidental discovery made using a zebrafish mutant known as "golden". Zebrafish is an ideal model organism because it has considerable genetic similarities to humans, enabling testing that would otherwise be impossible.

Cheng was initially looking for a gene that was causing a peculiar instability in the fish. The process of finding genes that have a particular function is called genome editing. It involves selectively knocking out genes from a species (which is done while it is still at the egg-stage) and then observing what difference it makes as the species is born and grows up. Repeating the process enough times narrows down the genes acting in the function of interest.

Their last knock out test was on the gene SLC24A5, which led to change in zebrafish's colour. This gene is found in humans, too, and it must have the same role. When Cheng compared the international human genome databases, such as HapMap and 1,000 Genomes, he spotted that SLC24A5 was found in all those with European ancestry.

While the discovery that a gene controls skin colour was huge, applications were not immediately apparent. That is until Cheng came across reports from the Surveillance, Epidemiology and End Results (SEER) program. The data indicated that people with European ancestry are approximately 20 times more susceptible to melanoma than those of African or East Asian descent.

Cheng reasoned the genes responsible for skin colour could also play a role in determining melanoma susceptibility. To investigate this, with Cheng leading the research, we collected more than 500 DNA samples from the Orang Asli, an indigenous Malaysian tribe. Our analysis helped narrow down the number of genes that determine skin colour in East Asians. But here we hit a roadblock: using just one population left us with more possibilities than we can test experimentally. In order to reduce the number of candidate genes to a manageable size, we needed to find another population with a similarly preserved, ancient gene pool.

This is trickier than it might seem. Globalisation means there are less isolated, indigenous populations with a similar genetic ancestry to the Orang Asli. There is one such population that still exists on the Caribbean island that Christopher Columbus spotted over 500 years ago and locals have now dubbed it "Nature Island". The island is the Commonwealth of Dominica, home to the indigenous Kalinago people, and it remains undeveloped.

Kalinago people have lived in reserve territory, which means we know very little about them. We don't share a foundation of friendship or culture with them. Our team visited the Kalinago territory twice this year in order to begin building relationships, hoping to familiarise them with us and our project. Our goal is to collect 500 samples from them voluntarily that will allow meaningful data comparison with the Malaysian tribe and help narrow down our list of candidate genes considerably.

With our narrower list of , we can begin testing their function using zebrafish mutants, as Cheng did in the 2005 research. Finding the genes responsible for East Asian's skin colour will kick off a new phase in melanoma research. We can compare the mechanisms and pathways of pigmentation in East Asians and Europeans, which can help find how melanoma occurs and drive the development of new treatments like .

Treating cancer via gene therapy has already proven successful. The most recent examples are the treatment of chronic lymphocytic leukemia and multiple myeloma. Is gene therapy an option for melanoma patients? Perhaps, but most importantly, we are getting closer to finding out.

Explore further: Studies of a skin color gene across global populations reveal shared origins

Related Stories

Studies of a skin color gene across global populations reveal shared origins

January 3, 2014
All instances of a gene mutation that contributes to light skin color in Europeans came from the same chromosome of one person who most likely lived at least 10,000 years ago, according to Penn State College of Medicine researchers.

Study of tribe could help find East Asian skin color genes

August 28, 2012
(Medical Xpress)—Genetic investigation of a Malaysian tribe may tell scientists why East Asians have light skin but lower skin cancer rates than Europeans, according to a team of international researchers. Understanding ...

Evolutionary medicine of skin cancer risk among Europeans

September 17, 2013
The proclivity of Spaniards to bask in regions like the Costa del Sol while their northern European counterparts must stay under cover to protect their paler skin or risk skin cancer is due in large part to the pigment producing ...

A genetic study on South Asians helps to understand human skin color variation

November 7, 2013
Though genetics of skin pigmentation has shown recent advancements in the last decade, studies involving populations of South Asia, one of the major hot spots of pigmentation diversity, is still in its infancy. In a recent ...

Individual gene differences can be tested in zebrafish

October 25, 2012
The zebrafish is a potential tool for testing one class of unique individual genetic differences found in humans, and may yield information helpful for the emerging field of personalized medicine, according to a team led ...

Sunlight adaptation region of Neanderthal genome found in up to 65 percent of modern East Asian population

December 17, 2013
With the Neanderthal genome now published, for the first time, scientists have a rich new resource of comparative evolution. For example, recently, scientists have shown that humans and Neanderthals once interbreed, with ...

Recommended for you

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.