Bone marrow cancer gene clues found

A gene defect increases the risk of a type of bone marrow cancer by 30%, the Daily Mail reported.

The news is based on an examination of people with multiple myeloma, a relatively rare type of cancer that starts in the bone marrow and can go on to damage the bones. By comparing the genetics of people with and without the disease, researchers found two genetic variations that were more common in people with multiple myeloma. These variations were associated with a 30% increase in the overall risk of a person developing multiple myeloma. Although it has long been known that relatives of multiple myeloma patients have a greater risk of the disease, this is reportedly the first study to identify genetic variations that are linked to it.

Although researchers identified these genetic variations, it is still unclear why they might increase the risk of multiple myeloma. Further work will be needed before these findings can help us understand more about the disease. It is likely to take considerable time before we know if the discovery can lead to new treatments. Also, not everyone carrying the genetic mutations will get myeloma, and not everyone with myeloma will carry these mutations.

Where did the story come from?

The study was carried out by researchers from the Institute of Cancer Research and other research institutions in the UK, Germany and Sweden. The main funding was provided by the charity Myeloma UK. The study was published in the peer-reviewed journal Nature Genetics.

Although most of the Daily Mail ’s coverage was accurate, it claimed that “scientists have made a key breakthrough in the search for a better treatment for bone marrow cancer.” However, so far researchers have identified two genetic variations that are associated with the disease, and it is not yet clear whether this finding could be translated into new treatments. The researchers have not been able to confirm how these mutations might increase cancer risk, let alone devise a way to treat them.

What kind of research was this?

Multiple myeloma is a cancer of one type of white blood cell that is present in bone marrow. It can cause bone pain, fractures and anaemia. In 2008, there were 4,516 cases in the UK (5.3 cases per 100,000 people). The causes of multiple myeloma are unclear, although relatives of people with the disease have a two- to four-fold increased risk of developing it, suggesting that genetic factors may contribute to the disease. However, even among relatives with a higher risk, the overall risk is still low.

The current research was a case-control study that aimed to identify genetic variations in DNA that are associated with an increased risk of multiple myeloma. In this type of study, researchers compare the genetic make-up of people with the disease (cases) with that of people without the disease (controls). If variations in a particular region of DNA are more common in the cases, then these variations, or variations nearby, may contribute to the risk of developing the disease. This type of study is appropriate for examining this sort of issue.

What did the research involve?

The researchers looked at the DNA sequence (called the genome) of 1,675 people with multiple myeloma and 5,903 individuals without multiple myeloma, drawn from the UK and Germany. The researchers looked for single “letter” variations in the participants’ genetic code, and hoped to identify variations that were present more frequently in individuals with the disease.

After identifying variations that were more common in cases than controls, they then attempted to replicate their results in a further sample of patients and controls. They did this by looking at the DNA sequence in the regions they had identified in 169 people with multiple myeloma and 927 healthy controls.

Within the code of the DNA are specific sequences that perform specific functions. These are known as genes. The researchers looked at the regions where the variations were located to see whether they were in or close to genes. They then looked to see whether these variations were associated with any change in the activity of any nearby genes.

What were the basic results?

The researchers identified variations in two regions of the DNA that were present more frequently in people with multiple myeloma. One variation was associated with a 32% increase in the odds of multiple myeloma and the other with a 38% increase in the odds.

Genes carry instructions for making proteins, and changes to their DNA sequence can cause changes to the protein they make. One of the variations (called rs1052501) lay in a gene, called ULK4, responsible for producing a protein, but the researchers found that this change was not predicted to affect how the protein works. Therefore, it was not clear if this change could directly contribute to the development of multiple myeloma.

The variation was also found to be close to a gene called TRAK1, which contains the code for making a “trafficking protein”, a type of protein used to move other proteins and parts of the cell around. It’s possible that nearby mutations may affect the trafficking protein and are responsible for the development of the disease.

The second variation (rs4487645) is present in another gene called DNAH11, but is not predicted to cause any changes to the protein produced by this gene. The variation is also close to another gene, CDCA7L.

There was no statistical difference in the activity of these four genes in cells from patients with multiple myeloma and control cells. This means that the researchers are still not sure exactly how the variants identified might contribute to causing multiple myeloma.

How did the researchers interpret the results?

The researchers concluded that the study has identified “new genomic regions associated with multiple myeloma risk” and that these might lead to greater understanding of the causes of the disease. However, they say that the association between the genetic variations and multiple myeloma is still unclear and will require further investigation.

They also say that the risk associated with these variations is modest, accounting for approximately 4% of the familial risk of multiple myeloma. Therefore, more variations are likely to be associated with the disease.

Conclusion

The causes of multiple myeloma are not known. However, they are thought to include genetic factors because family members of people with the disease have an increased risk of developing it themselves. This study has identified variations in two regions of DNA that are more common in people with multiple myeloma. These variations were each associated with about a 30% increase in the overall odds of developing multiple myeloma. However, other variations are likely to contribute to the risk as the two variations identified were estimated to account for about only 4% of the increase in risk in family members of people with multiple myeloma.

This is reportedly the first study to identify genetic variations linked to the disease. However, how these genetic variations might increase the risk of multiple myeloma is unknown. This will need to be investigated before these findings could be used to help us understand more about the disease and to develop new drugs.