A researcher looking at a gene sequence

Cancer Research UK has invested in gene-hunting technology

Our genes form the instructions that tell our cells what to do – when to grow, divide and die. These instructions are encoded in the form of DNA. The DNA code is made up of four “letters”, known as A, G, C and T.

Although most of our genes are similar from person to person, there are small variations within them. It is this variation that makes us unique.

But over the last decade or two, researchers have been finding that small variations in certain genes also seem to be linked to an increase or decrease in a person’s cancer risk.

At the moment, we only know about relatively few of these genetic variations that are linked to cancer risk. In order to understand more about how our genetic makeup influences our risk, it’s clear that we need to find more. So how do we do it?


Scientists have now identified regions scattered throughout our genome that differ by just one letter, or ‘nucleotide’, to give it its technical name. These variants are called SNPs (pronounced “snips”), which stands for ‘single nucleotide polymorphisms’. For example, an ‘A’ in one person might be a ‘T’ in another.

Since the completion of the Human Genome Project, the locations of tens of thousands of these SNPs on our chromosomes have been carefully mapped. In other words, researchers now know exactly which genes they are located within or near.

Recent advances in technology mean that scientists can analyse a person’s DNA, and figure out which versions of particular SNPs they carry. They can then see whether a particular pattern of SNPs in any region of DNA is linked to cancer. Researchers will scan across the DNA from a large number of people affected by a specific type of cancer (‘cases’), and compare their SNP patterns with those from people who are unaffected by the disease (‘controls’).

When embarking on a ‘fishing trip’ to look for new cancer-linked genetic variations, scientists start out looking at a relatively small number of SNPs scattered across the whole genome. This means they can get an idea of the general regions of DNA that are likely to harbour cancer genes. Then the scans are repeated using more closely packed SNPs in these specific regions, usually studying many more cases and controls.

So if people with, for example, breast cancer are more likely to have a certain pattern of SNPs across a particular region of DNA, then it is likely that a gene variation linked to breast cancer risk lurks there too. It’s important to note that SNPs themselves aren’t necessarily the gene variant that causes cancer (although they might be) – in this context they are just handy DNA “tags” that allow scientists to identify and track regions of DNA.

It is their sheer size that makes these studies work. Literally thousands – and sometimes tens of thousands – of cases and controls are needed to make sure the results aren’t just due to chance, and are applicable to the general population. And such large scale, whole-genome scans are only possible thanks to recent advances in technology.

Variation, not mutation
At this point, it’s worth noting that this is very different from hunting for “strong” inherited cancer predisposition genes. These include BRCA1 and BRCA2, which are linked to breast, ovarian and prostate cancers, and APC (linked to bowel cancer). A fault in one of these genes causes a cell to go seriously wrong, and greatly increases the likelihood it will turn cancerous.

People who inherit faults (mutations) in these so-called high-risk genes can have a lifetime risk of cancer as great as 80 per cent. This means that there’s an eight in ten chance of them getting a specific type of cancer at some point in their life. The changes in cancer risk caused by gene variants linked to SNPs are much smaller than that. But if a person has several “risky” variants, they could add up to a combined effect that may significantly contribute to their overall cancer risk.

The first large-scale SNP search for cancer genes was published in May 2007, and was partly funded by Cancer Research UK. Scientists funded by the charity went on to use the same method to track down new genes linked to bowel, prostate, lung and brain cancer, and the list still grows.

Other researchers around the world have also used the technology to search for genes linked to other complex diseases, including heart disease and the auto-immune syndrome lupus.

The implications
Often when we see a story in the news headed “New cancer gene found”, it begs the question, ‘will a genetic test be available?’ And this, ultimately, is the goal of many of these genetic studies.

But, sadly, it’s probably not as simple as using this data to develop a genetic test that gives a yes or no answer. What these SNP studies suggest is that future gene tests will have to look at the combined effect of many subtle gene variants, and their answers will be more ‘shades of grey’ than black or white.

As mentioned above, many of the genes identified by SNP studies only confer a very small increase in risk – that is, having the faulty version only affects your risk of cancer by a small amount. It’s also important to remember that genes aren’t the be-all and end-all of cancer risk. Our environment and lifestyle are key figures against the background of our genetic tapestry.

As we discover more about our genes, and the cancer risk they confer, researchers are also starting to unpick the complex interaction between nature and nurture. In the future, this kind of research will hopefully lead to a much more accurate way to predict an individual’s risk of cancer.

In turn, this will highlight people in need of extra preventative measures, such as screening or medication, or those who might benefit most from following a healthy lifestyle.


This article was first published in the Behind the Headlines section of our website. We have now moved this content to the blog.

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