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The genetic diversity that may explain differences in cancer rates across ethnicities

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Written by Cancer Center on May 13, 2019

Paul Norman, PhD, was born in the Midlands region of Central England in the county town of Shrewsbury, which, coincidentally, is also the birthplace of the naturalist and explorer, Charles Darwin. And like Darwin, Norman set out on a mission to categorize the diversity of life. Only, while Darwin concerned himself with things he could see – the beak shape of Galapagos finches, for example – Norman explores the diversity of cells hidden inside our bodies. Even more specifically, Norman, who recently joined University of Colorado Cancer Center as a mentored member, researches the diversity of tiny proteins that sit on the surface cancer cells. What seems little could be very big: Differences in these proteins across ethnicities could help to explain the differences in cancer rates between human cultures. 

“The human leucocyte antigen or HLA genes are associated with infectious disease resistance, and it’s increasingly becoming apparent they are also involved in many types of cancer,” Norman says. For example, many cancers mutate HLA genes, disabling their function. Without the cell-surface proteins produced by HLA genes, tumor cells can become invisible to the immune system.

However, the body has a way to counter this invisibility. In addition to T-cells that can recognize proteins produced by HLA genes, the immune system includes “natural killer” cells that target cells that have lost HLA proteins.

“Natural killer cells have receptors that recognize when HLA is lost, and when they do, they kill the tumor cell,” Norman says. One aspect of his work in the CU School of Medicine Division of Personalized Medicine and the Department of Microbiology and Immunology seeks to harness these natural killer cells as a treatment against cancer.

But like HLA genes, the makeup of natural killer cells varies by ethnicity, and so in addition to looking inside cells, Norman has adopted the strategies of big data to characterize HLA and natural killer cell diversity across human populations.

“My main focus for the last 10 years has been to establish this diversity across the world, looking at African, Oceanic, Asian, European and other ethnicities to get a feel for the implications of different genes and cells. Some of these genes correlate with the epidemiology of cancer types,” Norman says.

In other words, HLA genes and natural killer cells may help to determine what kinds of cancers are prevalent in which cultures. For example, breast cancer is almost three times more prevalent in people of European descent than it is in Asian populations. And, likewise, discovering which HLA and natural killer cells keep certain cancers at bay could influence the development of new immunotherapies against these diseases.

“CU immunology is pretty famous – it’s got a really good reputation – and the Division of Bioinformatics and Personalized Medicine is very new, with a groundbreaking philosophy promoting dynamic research, so I was really pleased to be offered a position here. It’s a world-leading institution” Norman says. 

Recruitment of promising young scientists like Paul Norman ensures that CU remains at the forefront of immunotherapies against cancer for many years to come.

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Paul Norman, PhD