Seventh update – Genes.

Early Feb 2019 – So pleased that January is over, it did drag on a bit. February brings the Six Nations Rugby, my 53rd Birthday and a bit more daylight!

I have just completed the 4th cycle of treatment and I must admit to finding it harder this time as it was deliberately a bit more intensive for the reasons described in the previous update. It has left me feeling tired with a few new side effects but nothing too serious and hopefully it will result in some faster progress so let’s see what the next set of tests reveal in a few weeks time. Now I have about a week off to regather and to get over a bit of a cold which caught up with me in the last few days, so time to take it easy, enjoy the rugby and look forward to a Birthday weekend with the family. There are another 4 rounds of treatment to go and then the transplant.

I have been thinking about Genetics and doing some reading which has been fascinating. It’s turned into quite a long note for the blog so there is not much room for other stuff this time, I seem to have run out of good rugby trivia for now anyway.

A lot of people ask me if my Myeloma is inherited or caused by genetic factors. The conversation is usually bit like this…

‘What symptoms did you have before being diagnosed?‘ – None whatsoever.

‘How was it spotted then?’ – I had a condition called MGUS* for many years which can progress to Myeloma. Everyone who gets Myeloma has MGUS first but the majority of people with MGUS never have a problem, most of them won’t know that they have it.

‘So how did you know that you had that then?’ –  My eldest sister died from Myeloma and during her treatment I was tested to be a stem cell donor and I matched very well so further tests were completed which discovered my MGUS. Sadly my sister was never well enough to attempt the transplant but that’s how I have known that I have had what is probably best described as a ‘predisposition’ to the disease for a long time and this has been monitored with regular tests over the years.

‘Aha, so it’s inherited then’ – Not so fast! Sorry but it’s not that simple. It has been known for many years that people with a history of Myeloma in siblings have a higher chance than most of developing the disease but it is still not a particularly high chance. The reasons for this have not been well understood but research is beginning to uncover some clues. There are clearly genetic factors involved but to put it into perspective the risk of developing Myeloma only increases by about 3 times if you have a sibling with the disease, add the presence of MGUS and the risk rises. Other complications include the fact that the sample sizes are very small, fewer than 10 in 100,000 people develop Myeloma in the first place so the incidence of siblings with the disease is small and studies are very limited by this. Also there are other factors involved, men and obese people are slightly more likely to develop Myeloma but there is no obvious connection with other lifestyle factors such as smoking or drinking. The most striking factors are all race related – Black males are roughly twice as likely to get Myeloma than White males while the incidence of Myeloma in Asia is significantly lower. This seems to point the finger at genetic differences and the research is very interesting.

Unlocking the secrets of the Genome… In a fascinating special supplement for National Geographic titled ‘The Future of Medicine’ there is a great piece about how fast and cheap it has now become to have your Genome analysed. A volunteer for the publication has her full genome sequenced in a few days at a cost of about a thousand dollars. A quick bit of Googling puts this into amazing perspective – the original US state funded Human Genome Project was officially launched in 1990 with a budget of over $3bn and the ambition to find a technology to unlock the detail of the full human genome within 15 years. A ‘rough draft’ was complete in 10 years and the project was considered complete by 2003, 2 years ahead of schedule due to to the rapid advance of sequencing technology and computing power.

Huge genetic databases and ‘Genome Wide Association Studies’ are now commonplace, helping scientists unlock the secrets of the Genome to predict our individual likelihood of developing certain diseases. Understanding cancer is a top target, not surprising when you consider that Oncology products are the biggest selling globally for the drug companies by quite a margin with worldwide sales approaching a staggering $100bn a year. Myeloma sits at about 18th on the list of cancers you are most likely to get with around 6000 diagnoses in the UK each year compared to around 60000 women diagnosed with breast cancer. Even for Myeloma the market is enormous globally with leading drug Revlamid approaching $10bn in global sales and growing fast. In persuit of these vast markets spending on R&D by the drug companies is huge at over $150m each year. Spurred on by these big sales opportunities, the new insights offered up by the Genome and other evolving technologies it is not surprising that we are in a golden age for the discovery of much more effective and innovative drugs and medical techniques.

Genetics and Myeloma… Unfortunately this story is not leading to a simple answer! There is no dominant Gene issue that predicts Myeloma. In some cancers Genes have been identified that have very strong statistically predictive ability, most famously in the BRCA1 and BRCA2 genes that prompted Angelina Jolie to have surgery rather than accept her high risk of developing breast cancer. Despite this it has been discovered that even without the BRCA genes there are other groups of women with high genetic risks of developing the disease due to complex combinations of other genetic markers; there is a lot still to learn. My understanding of the Genetic work on Myeloma is that it is combinations of high risk areas of the genome that are most promising to help us understand any inherited linkage and chances of developing Myeloma rather than a clear indicator like a BRCA equivalent.

My best attempt at answering the same question now? Is it inherited?

I am going to stick with the word ‘predisposition’ to best describe my chances of having Myeloma but It may well be that due to genetic patterns that we don’t yet fully understand the chances were higher than I perceived. Without full comparison of my genome with my sister, which is obviously not possible, I will never really know whether we were similarly at high risk or not.

A final thought on this – the vast majority of Myeloma patients have no affected relative, this is in contrast to other cancers and particularly breast cancer. So it’s probably a bit inherited but there is much that we don’t understand and many other factors involved. Of the c.6000 newly diagnosed Myeloma cases in the past year in the UK only around 20 of us will have had a family member with the disease.

More information from Myeloma UK:   www.myeloma.org.uk/documents/is-myeloma-an-inherited-cancer-infosheet/

* MGUS is short for ‘Monoclonal Gammopathy of Unknown Significance’ and is defined by the presence of an abnormal protein called a paraprotein or M protein in the blood.

It would not be a blog for me without a good quote. I don’t watch Call the Midwife (honest) but I have been catching the last few minutes recently as I settle down for Les Miserables and there is often a closing speech which is very well written and delivered. This one from the episode before last was particularly good and quite moving…

We can decide to be happy, make much out of little, embrace the warmth of our ordinary days. Life unfolds as a mystery. An enterprise whose outcome cannot be foretold. We do not get what we expect. We stumble on cracks, are faced with imperfection. Bonds are tested and tightened. And our landscapes shift in sunshine and in shade. There is light. There is. Look for it. Look for it shining over your shoulder, on the past. It was light where you went once. It is light where you are now. It will be light where you will go again.

For those of you that have persevered all the way to the bottom of the page here I am going to reward you with the most amusing picture of myself that I have…

Bristol zoo, early 1970’s, clearly not impressed and I still don’t like monkeys!