Being human

The human body - a summary!

Please stop for a moment and think about this....

Most of the time you probably think of yourself as the person you are - your name, your background, your personality, your interests, your loves, your fears, the things you do. Containing all of that in one package is your human body. Most of the time you take most of what your human body does for granted. You have no real idea about all of the things that are going on in your body at any given moment that keep you alive and functioning.

The instruction manual for your human body is your genome. Your genome is made of 3 billion DNA "base pairs" - or, 4 letter chemical codes. Around 3% of these chemical codes spell out genes. You have around 24,000 genes. Scientists are learning lots about what these different genes each do to make your human body live and function. (And from what I can tell they have not yet worked out what on earth the other 97% of your 3 billion chemical codes are doing.)

When I stop and actually think about these numbers, I realise how incredible the letter I got in the post yesterday from Leicester's Department of Clinical Genetics really is.

Dear Sarah, ...

"...As you are aware we have carried out further tests into the cause of your breast cancer and your wider family history of breast and ovarian cancer. We have now received the results which has identified a significant alteration in the PALB2 gene...."

This is BONKERS! To try and find the cause of my breast cancer (and the breast and ovarian cancers in my family), clever scientists out there have been scrutinising 97 of my genes that are considered to be relevant to breast cancer risk. And they've found it, in the gene called PALB2.

Just to put this in to perspective again...

In amongst the 3 billion DNA base pairs that make up my genome, based on previous studies and research, scientists identified 97 sets of DNA base pairs (genes) to look at. One of them was the PALB2 gene which itself is made up of 38,195 base pairs of DNA (ie, 38,195 pairs of 4 letter chemical codes). That's where they found the error that caused me to have breast cancer at age 33. Think of it as going in to the British Library, being told that somewhere in one of the books is a typo, and that you have to try and find it. You're given a few clues to narrow down which sections it would be best to search in although no guarantees they are the right sections. Needle. Haystack.

Wow.

So, what's wrong with me?!

Lots, haha! But focussing on the genetics... We already knew there was something genetically wrong with me that increased my risk of breast and ovarian cancer. The family history plus my own diagnosis at such a young age made that obvious. What's changed is that they now know exactly what kind of defective mutant I am, and from what I can tell, this is good news. Knowledge is power.

Your body is made up of trillions of cells, and all sort of things go wrong with many of those cells every day. Certain genes, like PALB2, play a part in spotting when that happens and fixing it, preventing a cancerous tumour from developing. (A cancerous tumour starts with one single cell that is faulty. A cell that should have, for example, been the cell of a milk duct, becomes an out of control monster, no longer concerned with it's job of being a milk duct cell, but only with dividing and multiplying in to new monster cells, that divide and multiply in to new monster cells and so on and so on, taking over the space in your body and preventing other cells from doing their own jobs of keeping you alive and functioning well).

So, one of my genes, PALB2, is not doing it's job properly. One day, somewhere in my body, one single cell got all messed up, and became faulty. Instead of being spotted and then repaired or killed off, it was ignored or got missed, and was able to divide in to two new messed up cells. Those two new messed up cells each divided in to two more new messed up cells, and so it went on until there were enough messed up cells there to form a tumour.

What now?

The error in my PALB2 gene caused my breast cancer. That error in that gene is still there in all the cells in my body, and could cause another, new breast cancer and possibly an ovarian cancer too in the future. So I go on ahead as planned with preventive surgeries, knowing that this is the absolute right move. To put it bluntly, my surgeon is removing all breast tissue from my body and reconstructing with muscle from my back, and implants. Fake boobs, but ones that won't be on a mission to kill me. And the ovaries will be chopped out soon too. It doesn't mean I am completely risk free - it's not possible for the surgeon to guarantee every breast cell has been removed, but my risk of a new breast cancer or ovarian cancer will be very low, and lower than the population risk (ie the risk of any random woman in the population who has no family history or genetic error).

Medically, other than that I'm not yet sure - I need appointments with the Genetics Clinic, my oncologist etc. But this information might help them to give me better targeted drugs to reduce the risk of recurrence of the cancer I already had, and I wouldn't be surprised if I am asked to be included in various genetics studies and things.

But there is another thing.... I KNEW there was something genetically wrong in my family and I KNEW it wasn't BRCA1 or BRCA2 but I KNEW I was at high risk. I bloody knew it, and I was right. (I always am. Sometimes people think I am not right, but I am always proven right in the end my friends, always. True.) I know lots and lots of young women in a similar position to me - breast cancer diagnoses but no BRCA fault. No BRCA fault is not necessarily good news  and does not necessarily mean a cancer was "just one of those random things" - you can still be at high risk from a fault in another gene such as PALB2 and I am living proof of that. I intend to advocate for women and families at risk of hereditary breast and ovarian cancer (HBOC) where no BRCA fault has been identified. I am going to advocate for these women to have access to increased surveillance, and preventive options such as surgery. It can mean the difference between life and death.

I would love to hear from you if:

• If you have a PALB2 mutation too! I don't know anyone else with one yet!
• If you have a strong family history of breast and ovarian cancer but, after genetic testing, have no BRCA1, BRCA2 (or other such as P53, CHEK2) mutation identifiable in your family.

My own cancer treatment is my priority for now, but as soon as I can I will be collating information about PALB2 and translating it in to plain English, for myself and for anyone else who'd find it useful.

And tonight I am going out with a friend and I am going to have a drink and make a toast to SCIENCE!

Incredible. Just incredible.