Topic: Genetics - The elephant in the room???

Just thought i'd put up a post to sound our everyones views on the possible genetic determinents of Cholangiocarcinoma.

Does anyone have any knowledge on this?

Are Physicians talking about possible genetic "causes" of cc?

What information do physicians need to know in order to investigate possible genetic causes (family history etc etc)

What are the possible barriers to discussing genetics...how real are they e.g. fears over insurance cover, ethical issues over the use of genetic discoveries etc etc?

Frogspawn

Re: Genetics - The elephant in the room???

Frogspawn,
From my previous posting you know I favor the probability of a genetic connection.  However, the doctors (and I have discussed this with several) all seem to think there is not. 
Karen

Wishing all God's blessings!

Re: Genetics - The elephant in the room???

Hi Frogspawn,
Interesting that you should bring this up.  the gastrointerologist I saw at Emory Crawford Long is interested in the genectics side of things.  He was interested that my father had been exposed to asbestos in the 1950's while he was in the Navy.  My father died in 2000 from mesothelioma.   Dr. Martinez said it would not be improbable that there was a connection if my Dad's DNA had been altered by his exposure to asbestos (I was born in 1965).
However, as a child I also played in creeks and streams that were more than likely contaminated with PCB's.   I have not pursued this though.
Is there any history of asbestos exposure in either of your parents?

- Suzanne

4 (edited by Frogspawn Sat, 06 Sep 2008 09:35:00)

Re: Genetics - The elephant in the room???

Look at the literature relating to mismatch repair genes these are implicated in cc but cc doesnt get much airtime because these gene defects usually manifest themselves through causing other types of cancer (mainly colon).

Apparently there are known to be 5 of these mismatch repair genes which are capable of mutating.

Of my generation and my fathers generation the spread is as follows

sister Hysterectomy
brother 1 49 died cc
brother 2 ok

Father died cc 69
Uncle died cc mid to late 50's
Uncle 2 died pancreatic cancer mid to late 50's

I only mention this to show that cholangiocarcinoma isn't always rare in familial cancers and we can't be the only ones!! This looks like a pretty high incidence of cc to me. Although there are other instances of colon cancer (and some of these people had colon cancer as well) these instances of Cholangiocarcinoma are PRIMARY cancers...not secondaries.

http://ctd.mdibl.org/
This website links genes to diseases...and looks quite clever. If you know of a gene that is associated with cc then you can find out exactly how. Also links chemicals to genes and diseases as well.

The environment gene interaction thing is very interesting...no specific info on my dad but you never know... his father died of colon cancer so the mutation  (whenever it took place) occurred before then..

Sorry to hear about your pop.

Re: Genetics - The elephant in the room???

From cancer.net

Hepatobilliary cancers comes third on the list for commonality...

What are the estimated cancer risks associated with Muir-Torre syndrome?

General cancer risks for people with Muir-Torre syndrome

Colorectal cancer  80%
Stomach cancer  11% to 19%
Hepatobiliary tract  2% to 7%
Urinary tract  4% to 5%
Small bowel (intestines)  1% to 4%
Brain or central nervous system  1% to 3%
Skin cancer increased risk

Cancer risks for women with Muir-Torre syndrome

Endometrial cancer  20% to 60%
Ovarian cancer  9% to 12%

6 (edited by JeffG Mon, 08 Sep 2008 17:36:46)

Re: Genetics - The elephant in the room???

Frogspawn... I have read along the way of all my researching, some articles about genetic involvement with cancer.  The discussion or debate is out there but I haven't seen that much information flowing.  I personally feel it certainly plays a role in some cancers, any cancers if the predisposition is there.  From conception to enviornmental and anytime in between. We could have a missing gene to begin wth, Gene interaction and loss due to other diseases, or enviornmental causation.  I'm far from being a science guru, I think we all have the genes suseptable for cancerous growth, and many variables surround us that are triggers for different types.  Well, that's about all my thoughts in this scientific realm.  I certainly believe genetic and enviornmental interaction should be investigated.  You have sparked my interest in this area again.  Thanks for the link ,I'll be checking it out.

Cheerio,
Jeff G.

Take it to the Limit,One More Time! (Eagles)

Re: Genetics - The elephant in the room???

Thanks Jeff.

As you can tell i'm no expert. Genetics is interesting isn't it? Nature, nurture and everything in between is involved... What is the mutation, what causes the mutation, how can we repair the mutatation...?

Mismatch repair genes are an interesting topic... With some of the websites the language is hard to understand and not so accessible for simpletons like myself...but some of them have some very good reviews that are vaguely comprehensible with a bit of time and effort.

With Torre Muir syndrome it is believed there is significant under reporting because not a lot of physicians know anything about it so they never identify it when problems occur...

Personally i also think that my own familys experience of hepato billiary problems suggests that the 2-7% represents under reporting... if we can change that then it could get more people interested in examining causes and possible cures for cc.

Most importantlly, if nothing else, if more people identify a genetic issue it can help them to help and their relatives get better screening and aid early detection.

You know (more than most i guess) that with current medical knowledge and technology that by the time the itching, yellow eyes, loss of appetite and weight loss comes, things have very often progressed too far to do anything too meaningful to help the majority (present company excepted!!)...and what we are left with is chemo, radiotherapy and some other relatively new techniques...none of which involve a cure.

My hope is that, at least for those with a genetic "cause" they give themselves time, through screening,  to get in there early an do something about it!!

Thanks for your interest in the topic. How are you doing?

Frogspawn

8 (edited by JeffG Tue, 09 Sep 2008 11:53:11)

Re: Genetics - The elephant in the room???

Hi Frogspawn,   Thanks for asking.  I'm holding my own, staying busy with home projects, and popping my morphine.  About five more weeks or sooner I'll decide my next course of action.  I have been putting weight back on since sticking to the 3 a day Ensure plus meals.  At least my rings aren't sliding off my fingers anymore.  Now if I can get my pants to do the same. Ha!  Also my attitude has been pretty good since practicing EFT.
You know genetics is interesting, like you said when it's in laymans terms.  I associate it mostly with Down Syndrome.  My friend had a baby with it.  Just one, in this case just part of one extra #21 chromosone causes this syndrome.  It's possible I have a missing link, as my Dad was involved in the testing of the nuclear bomb (hot Area) and got contaminated prior to my conception.  Shortly after he had cancer in his upper arm and radiation sickness from what iv'e been told.  His arm, well they did not leave much meat.  The whole bicept area had to be cleared.  Then later on down the road he developed on  both leg calves severe itchy raw type rash that never went away . Just kept treating it with something.  I pushed him to apply for disability and they interviewd him and said no relation.  then 8 years later it became public about location ,date , and time of testing and entitlement should be applied for.  But he was so stubborn and having already gone through the process, he ignored it and just pressed on with life.  Well, I better put on the brakes, rolling along here. 
God Bless,
Jeff G.

Take it to the Limit,One More Time! (Eagles)

9 (edited by Frogspawn Thu, 11 Sep 2008 07:09:18)

Re: Genetics - The elephant in the room???

My Dad used to take those meal in a drink things... i tried one. They taste like they have got lots of iron in them...yuck!

Would be good if we could get a doctor to do a post on the genetics side of things. I am trying to get somone in the UK to do something...i'll let you know how i get on...

(Your mention of the nuclear testing is something i've not heard of before...but i noticed someone else mentioned it on this site as well) Thanks for the info as will definitely investigate! Thanks.

Re: Genetics - The elephant in the room???

I also am interested in the possiblity of a genetic link. My husband passed away 9-2-08 of this terrible disease after only 7 weeks.  Our sons questioned the possiblity & the doctors for the most part seem to feel there is no genetic connection. However none of their answer were a firm NO. We feel there could be a link & would be interested in anything anyone can come up with on this subject.

Thanks,
Darla

"One Day At A Time"

All of my comments and suggestions are just my opinions and are not a substitute for professional medical advice.   You should always seek the advice of your physician or other qualified health care providers.

Re: Genetics - The elephant in the room???

Darla i saw your post in the introductions section. So desperately sad. I know you will feel like you have been robbed. I want you to  know that i am thinking of you right now and praying for help for you to get through the bad feelings you will be going through at the moment.

There are a number of people on this site who look like they have some king of familial cancer issue. There are some good explanantions on the publicly available health sites... medline... cancer.net. etc about the different possible genetic conditions.

In the UK we have regional genetics centres with genetics counsellors though you have to be referred to them by a GP or other consultant. There are some criteria called the amsterdam criteria that they use to decide whether it is worth doing a genetic test. I think they have something similar in the US...?

Frogspawn

Re: Genetics - The elephant in the room???

Thanks Frogspawn. 

I do appreciate your kind words & support. Everyone here is so helpful & caring. We are all going through this in different ways & need all the help & support we can get. I am hoping I can also help others that come here as, unfortunately, I now can honestly say that I know what they are going through as so am I. I will keep checking into the genetic side of this. Thanks for the info.

Darla

"One Day At A Time"

All of my comments and suggestions are just my opinions and are not a substitute for professional medical advice.   You should always seek the advice of your physician or other qualified health care providers.

Re: Genetics - The elephant in the room???

As far as genetics go, I'm the only one in my extended family to have any GI cancer.  There is breast cancer in the maternal side of my family, so I always figured I'd be fighting that eventually.

Re: Genetics - The elephant in the room???

Hi Lisa...thanks for your post.

The fact that they are different types of cancers does not necessarily mean that it is not genetic. Faulty mismatch repair genes are assocaited with lots of different types of cancers including GI, hepato billiary, colon, urinary...see figures above.

Re: Genetics - The elephant in the room???

Hi everyone,
The discussion of CC being hereditary is an interesting one. But also a subject that didnot have enough research yet. A lot of oncologists in Holland think the chance of getting cancer might be hereditary. And I tend to agree, looking at my husbands background. His mother kicked off two different types of cancer, before she died on asbestos cancer. Both her brothers died on prostate cancer and two of their sons also had cancer.
On the other hand, what can one do with this knowledge? Not much, I believe. Talking to our oldest son about this and trying to get him to eat healthier, he answered with a smile "I rather live 60 years with a lot of fun, than 80 years with a lot of restrictions". As you might guess, he is a junkfood eater.
Anyway, on our anti-cancer diet my Peter is doing quite well. We will have the results of today's bloodtest on Wednesday. The last bloodtest was not an improvement, but also not worse. The coughing (metastases to the lungs) remains.
Wishing you all the best, Iris.

Re: Genetics - The elephant in the room???

Hi Iris

Good to hear that the fight goes on! Your hubby and his family (yourself included) look like you have suffered a lot.

When the metastses spread it is quite upsetting isn't it? The coughing is so distressing...you wish you could do something to help them cope! My brother had them in the bottom of his lungs too.

I  think you should say to your kids that even if they dont want to change their diets...at least it could help with sccreening..getting things early would help especcially with cc and help them prolong the lives they are enjoying!!

Glad you tried though...good on you!

17 (edited by jules Mon, 13 Oct 2008 02:28:24)

Re: Genetics - The elephant in the room???

frogspawn,

I think you are onto something here.  My Dad's uncle died from 'liver' cancer.   That was some time ago, and the circumstances are vague, I'm guessing it was cc.  (My Dad died from cc 23/9/2007)

I went to my gp about this and I was referred to a genetic consultant who was dismissive.  I do not feel reassured.  So little is known about this disease how can they be so sure?

I did come across a clinical trial in Switzerland asking for blood relatives of cc patients to trial some type of screening - If I recall correctly it involved taking samples of the cells lining the bile duct for testing - I think it was called brush cytology - or something like that.. I will try to dig it out.

surely if we are wanting to make some progress towards a cure/early diagnosis then this needs to be taken seriously.  Thankyou for your informative postings on this subject.

18 (edited by Frogspawn Mon, 20 Oct 2008 09:24:25)

Re: Genetics - The elephant in the room???

Thanks Jules

If you don't mind me asking did they offer you genetic screening? IT would be interesting to hear from you the rationale for their dismissive attitude...(if you feel you can share).

In the UK they have a laborious preparation process before they will actually do the test... they want  to make sure that you don't have any mental health issues if you are found to have a genetic predisposition.

I believe both my surviving brother and sister have got "The Dodgy Gene" and some of their children... so they are taking the necessary precautions and getting involved in screening programmes... though for some reason they seem to want to focus colonoscopies, gastroscopies rather than anything else...

I have seen a Swiss piece of research conducted on Torre Muir Syndrome... which looked at genetics. IT was quite interesting because they downplayed the incidence of cc... i tried to get them to think a little more about it but don't know if that had any impact... IF you can add anything on what you have seen that would be good.

One other thing i have noticed is that Surgeons don't seem to be that interested in the genetics side of things... have you noticed that???

Re: Genetics - The elephant in the room???

Marions piece of info on genomics looks interesting so i think i will have a look into that as well!

Re: Genetics - The elephant in the room???

My husband was diagnosed with cc and then when they attempted the whipple procedure they found another tumor on the pancreas that didn't show up in any of the tests.  He has 3 people on his mothers side that died of pancreatic cancer.   His doctor has said that it's probably genetic for my husband.  It's definitely a subject that should be researched and talked about.

Re: Genetics - The elephant in the room???

When my mom was seen at MD Anderson for cc, they sent her for genetic counceling. My maternal grandmother had pre-cancerous polyps in her colon, and Her mother died of colon cancer. They told us that the family may have Lynch Syndrome. This gene mutation causes colon, liver, cc, and ovarian cancers.  They are testing her biopsy slides for this. We should know more when she goes back to Houston in January.

Re: Genetics - The elephant in the room???

Suzannegm wrote:

Hi Frogspawn,
Interesting that you should bring this up.  the gastrointerologist I saw at Emory Crawford Long is interested in the genectics side of things.  He was interested that my father had been exposed to asbestos in the 1950's while he was in the Navy.  My father died in 2000 from mesothelioma.   Dr. Martinez said it would not be improbable that there was a connection if my Dad's DNA had been altered by his exposure to asbestos (I was born in 1965).
However, as a child I also played in creeks and streams that were more than likely contaminated with PCB's.   I have not pursued this though.
Is there any history of asbestos exposure in either of your parents?

Holy Cow! I could have written this! My grandfather died of lung cancer in 1986 believed to be caused by asbestos exposure. Of his 7 children, 4 (maybe 5, not sure on 1) have been diagnosed with cancer. Three of those have passed away as a result. My father survived colon cancer in 1995 and was diagnosed with CC in late October. Of  his remaining 3 siblings, one is in her 80s and appears to have dodged it, the other is the youngest, and okay so far and the one I am unsure, but I think he has had malignant colon or bladder polyps removed.

I have a number of digestive problems: had my appendix removed and my gall bladder removed and still suffer from pain that has been tentatively diagnosed as biliary dyskinesia. My only sibling has irritable bowel syndrome.

I have long thought, as many on here do, that some folks' cells have a propensity to mutate to cancer and others do not. I guess two people could be exposed to exactly the same thing and have different outcomes.

I HATE this disease.

23 (edited by Frogspawn Wed, 07 Jan 2009 17:24:39)

Re: Genetics - The elephant in the room???

Robyn... I think Torre Muir syndrome is probably an old term... i think that my families problem is probably classified now as Lynch Type II syndrome... I think that a number of these syndromes actually involve mutations in a number of the same "mismatch repair" genes that mean that mutated cells aren't repaired by the body as they should be. My surviving brother is a carrier of the gene as is my sister. Apparently the genetic condition is autosomal dominant which means that each child of a carrier has a fifty fifty chance of inheriting... I pray for a negative test for your mum but the strength to bear a positive one.

As suzanne and walk have mentioned maybe there could be an environmental component that can trigger the gene fault...'

Walk, if i was your sibling, with a family history like that, i'd be down to the doctors for a colonoscopy (i'm not a doctor by the way!)

Re: Genetics - The elephant in the room???

I do have a colonoscopy and other check ups regularly . All of this cancer business and discussion has put a nagging into my head to go to the doctor for a once-over in the near future.

My question is: are there certain blood tests that I should ask for? tumor markers, etc?

Re: Genetics - The elephant in the room???

Very interesting discussion going on here! Thanks to all for sharing!
My Dad, who was recently diagnosed with unresectable intrahepatic cc (Nov.3), is a 5-year colon cancer survivor.  I also question the potential impact of environmental factors. My husband's grandfather (also local) died of cc in 98' (long time farmer), and another gal on the board just lost her husband to cc (about 20 miles up the road).  This region in our town of upstate NY is proving to be a an 'unofficial', cancer cluster- including cancers of all kinds.

-Tess