Gene mutations that could triple the risk of bowel cancer have been found, reported The Guardian . There are “two genetic variants that could triple a person's lifetime risk of developing bowel cancer” and up to a third of cancers that develop could be associated with the newly identified variants, the newspaper explained.
Prof Ian Tomlinson, who led the work at Cancer Research UK's London research institute pointed out in the newspaper that "the lifetime risk [of bowel cancer] is about 5% in the UK so it's going up to 7% or so if you've got both bad copies of a variant."
This study has identified variants that are associated with an increased risk of developing bowel cancer. However, the actual risk of developing bowel cancer is low in most people, with the possibility that several genes, as well as environmental factors play a role in its development. The cost of testing and the rarity of the variants identified by this study may limit the usefulness of genetic screening in the near future.
Where did the story come from?
Dr Emma Jaeger and 33 colleagues from a variety of Genetics and Cancer institutions across the UK contributed equally to this work, which was principally funded by Cancer Research UK. The study was published as a brief communication online in the peer-reviewed scientific journal: Nature Genetics .
What kind of scientific study was this?
This study included two main parts, a family genetic study, and a genome-wide association study, both of which are specific types of case-control studies. In a previous study, the authors located a region on chromosome 15 – CRAC1 – associated with a condition called hereditary mixed polyposis syndrome (HMPS). This is a condition which significantly increases the risk of bowel cancer risk in a group of Jewish people of Ashkenazi descent. This genetic location, called a locus, was found to lie in a long stretch of DNA and was identified by looking at five Ashkenazi Jewish families with HMPS; the presence of this gene was shown to increase bowel cancer risk.
In this new study, the researchers identified and analysed the genes from nine more Ashkenazi individuals, eight who suffered from HMPS and one who was unaffected, in an attempt to narrow down the CRAC1 disease locus to a more specific area of chromosome 15. The researchers managed to define a shorter length of the chromosome that contained three genes known to be related to colon cancer, but they did not identify any mutations that were unique to the individuals affected by HMPS.
In the second part of the study, the researchers suggested that the particular area of the chromosome they identified could contain variants that might increase the risk of bowel cancer in ethnic groups other than Ashkenazi Jews. The researchers analysed 145 variations in the DNA, called single nucleotide polymorphisms (SNPs), all of which lie within this area of chromosome 15. The DNA sequence of 718 cases (people with colorectal cancer, and a family history of the condition, or an early onset) was then compared with the DNA to 960 matched unaffected controls and the researchers looked for specific variations that might be linked to HMPS and increasing colorectal cancer risk. Several SNP variations in the region showed an association with colorectal cancer, but the researchers were unable to demonstrate a significant association after they made adjustments for the large number of comparisons they carried out.
In the third part of the study, the researchers took the two SNPs which showed the greatest association with colorectal cancer risk in the second part of the study (rs4779584, and rs10318), and looked for these SNPs in a larger set of 7,961 colorectal cancer cases and 6,803 controls.
What were the results of the study?
By pooling the data from all the cases and controls they studied, the researchers estimate that the variant on chromosome 15 (15q13.3 – rs4779584) is present in about 15% of colorectal cancers. Although they acknowledge that this locus may only account for about 1.5% of the excess risk seen in families with the disease, it could potentially be “an important contributor to the overall risk”.
The researchers also used the larger series to estimate that individuals carrying both the different SNPs at rs4779584 and at another uncommon colorectal cancer (CRC) locus on chromosome 8 (8q24.21 – rs6983267) have a two to three times increased risk of CRC.
What interpretations did the researchers draw from these results?
Prof Ian Tomlinson, who led the research, is reported as saying: "Increasing our understanding of genes like this may make it possible for scientists to eventually develop ways of stopping many people at increased risk of bowel cancer from developing the disease altogether."
What does the NHS Knowledge Service make of this study?
This initial report from a large study may have major implications for screening and treatment of bowel cancer, as the authors claim. However, the two-to-three fold increase in risk of colorectal cancer that the newspapers quote refers to the possible increase in risk if people carry the risk variant identified in this study, as well as another risk variant. This figure is only given as an estimate by the authors and the calculation supporting it has not been presented in the paper. Before this three-fold increase in risk is confirmed, further expert commentary on the full publication will be needed. Also, further research into any treatments proposed and any screening programmes will be needed before the hope offered by these researchers can be justified.
Sir Muir Gray adds...
Instead of talking about bowel cancer, we should probably talk about bowel cancers because it is now clear we are dealing with a number of different types of cancer, each of which will need its own particular prevention and treatment strategy.