Could new gene markers herald better cancer tests?

Thursday March 28 2013

Most of the UK media have reported on what has been described as landmark research into the genetics of breast, ovarian and prostate cancer. Many commentators state that this will lead to cheap and reliable screening tests for the cancers within "five years".

The news is based on the results from the Collaborative Oncological Gene-environment Study (COGS), which is an international collaboration involving hundreds of researchers. It looked at the genetic markers of more than 200,000 people to detect genetic variants that were associated with an increased risk of three types of cancer:

Previous research has identified genetic mutations that can increase the risk of breast cancer, such as the BRAC1 and BRAC2 mutations. The latest research identified more than 70 new variants, located in specific areas of human DNA (known as positions or loci), that are associated with an increased risk of breast, prostate and ovarian cancer, including 41 loci that are associated with increased risk of breast cancer.

This research does have the potential to lead to more accurate screening for certain types of cancer using relatively simple and cheap DNA testing, such as saliva or blood tests. But claims that these tests are “five years away” could be premature. It remains to be seen what effects these new insights into the genetics of cancers will actually have.

Where did the story come from?

An international team of researchers is participating in the Collaborative Oncological Gene-environment Study (COGS). COGS is a European Union funded project, with additional funding from Cancer Research UK and the US National Institutes of Health.

COGS has today published 13 papers in five journals. Several of the papers have been published together in a special iCOGS Focus issue of Nature Genetics, along with commentaries and a guided tour of the research.

In this story we will be concentrating on the identification of 41 new genetic regions associated with breast cancer.

This study was led by researchers at the University of Cambridge and funded by Cancer Research UK and the European Community. It was published as part of the iCOGS Focus issue in the peer-reviewed journal Nature Genetics.

Much of the news reporting concentrates on the possibility of using the results of these studies to design a genetic test for cancer. It is possible that future cancer screening could be improved by the use of genetic information – for ‘risk-stratification’, which is determining how great someone’s risk of developing cancer is. However, it is likely that such a programme would be complex, and the issue of how genetic data will be stored and used will have to be addressed.

It also remains to be seen whether routine screening using gene testing would be affordable or cost-effective. So claims that genetic screening for cancer is five years away could be premature.

What kind of research was this?

This was a case-control study that aimed to identify genetic variations that increased the risk of developing breast cancer.

What did the research involve?

The researchers were looking at what are known as single nucleotide polymorphisms or SNPs.

The human genetic code (human genome) is made up of information contained within our DNA. This sequence is made up of strings of molecules called nucleotides, which are the building blocks of DNA.

SNPs occur when the DNA sequence varies by a single nucleotide. Some SNPs have been associated with significant effects on human health.

While the entire COGS project looked at SNPs thought to be associated with prostate, ovarian and breast cancer, the study we are analysing just looked at breast cancer.

SNPs associated with risk of breast cancer were identified by combining the results of nine previous studies. The researchers investigated whether these SNPs were present more frequently in people who developed breast cancer by comparing 45,290 people of European ancestry who developed breast cancer with 41,880 who did not.

What were the basic results?

Variations in the DNA sequence at 27 different positions (loci) in the genome have previously been found to be associated with breast cancer risk. In this study, all but four of these previously identified loci showed clear evidence of association with breast cancer in this study (three others showed weaker association, and the other one was not investigated).

In addition, the researchers identified 41 new loci that were statistically significantly associated with the risk of breast cancer. Each locus was associated with a small increase in risk of breast cancer.

The researchers estimate that the 41 newly associated loci explain approximately 5% of the familial risk of breast cancer.

The researchers also state that a larger number of loci could contribute to susceptibility to breast cancer, suggesting that 1,000 additional loci are involved in breast cancer susceptibility.

How did the researchers interpret the results?

The researchers conclude that they have identified “more than 40 new susceptibility loci, more than doubling the number of susceptibility loci for breast cancer”.

The researchers go on to state that “the currently known loci now define a genetic profile for which 5% of the female population has a risk that is [equivalent to] 2.3-fold higher than the population average and for which 1% of the population has a risk that is [equivalent to] 3-fold higher”.


This interesting research has identified 41 new genetic loci that are associated with increased risk of breast cancer. Other studies performed by the COGS identified a further eight genetic loci, which, combined with the 27 previously identified loci, brings the total identified to 76. This is in addition to mutations in ‘high risk’ genes such as BRAC1 and BRAC2.

This research has the potential to lead to genetic profiling that may aid in identifying women at an increased risk of developing breast cancer (as well as women at increased risk of ovarian cancer and men at increased risk of prostate cancer).

However, it is likely that such a programme would be complex because, in addition to genetic testing, the results would have to be integrated into a risk assessment process, and care pathways for people in different groups would have to be developed. The issue of how genetic data would be stored and used would have to be addressed. Therefore, it seems unlikely that genetic screening will be introduced in the near future.

Nonetheless, this remains important and impressive research. Any advances in our understanding of the genetics of cancer are valuable and the study could be the first step to improving screening programmes for breast, ovarian and prostate cancer. It may also improve our knowledge of these diseases, and aid in the design of prevention and treatment strategies. But much more work will need to be done to reach these goals.

Analysis by Bazian
Edited by NHS Choices