Genetics & Rheumatoid Disease: More Complicated Than Cancer? | Rheumatoid Arthritis Warrior

Genetics & Rheumatoid Disease: More Complicated Than Cancer?

No one wants complicated answers, of course. But some answers are complicated, with multiple layers or causes. Like Rheumatoid Disease and childhood hearing loss. Instead of differing experiences of patients being  suspect, they should be valuable clues to answers we all seek.
DJ & Kelly shadow

Answers and more questions

The past few months have been a slow process of diagnosis with my son Roo’s hearing. This is not the first time I’ve walked this road, but each time it was different. A few years back, when Roo was only a toddler, his older brother and sister had CT scans evaluated by a specialist who finally put a name to their hearing loss, Mondini syndrome: an incomplete cochlea. It was good to have an answer.

Much later that I learned Mondini syndrome is not “just deafness” any more than Rheumatoid is just arthritis. It was good to have more complete answers that explained more of our experiences.

And now, I’m learning more. And have more questions.

People ask about a gene for Rheumatoid Disease, but it’s not that simple

Fifty to sixty percent of the risk of Rheumatoid Disease (RD) is considered genetic. RAW has discussed genetic links to RD several times (click here) including a guest series by Dr. Robert West covering some basic issues on genetics and genomics. But I had a revelation last week during a conversation with one of Roo’s doctors, a geneticist trying to help figure out what is happening with his hearing.

The most obvious clinical aspect of Mondini syndrome is a partially formed cochlea, but Roo’s cochlea looks fine. So it’s possible that Roo has something else wrong inside of his cochlea, or that he has a normal cochlea, but a large vestibular aqueduct (another of the three findings described by Mondini in 1791). How does this relate to Roo’s family history?

The doctor offered new information:

  • There may be multiple causes of Mondini syndrome; all Mondini is not necessarily caused by the same gene
  • Scientists now believe some of them could lead to milder hearing loss
  • A particular genetic combination could contribute to Mondini in one person, but a different type of hearing loss in another person
  • Some genes that can cause Mondini may cause problems in other organs also

My mind quickly made a comparison to RD. In an article on Rheumatoid biomarkers I’d read last summer:

“In cancer,” says Robinson, “a single genetic biomarker can completely guide treatment because that single gene is causing the disease. In contrast, RA appears to be polygenic — we believe that 10 or 20 or more genes may work together to cause susceptibility to the disease.”[1] (See note below.)

It makes sense that we are not all the same.

We don’t know enough, it’s complicated, and patients must be believed

The most important thing I’ve learned is how little we know – how little doctors know. At about eleven months of age, my son DJ had his first audiogram. As I watched him through a window in the soundproof booth, I could tell the results were not good. But nothing could prepare me for the young audiology assistant’s words: “He needs hearing aids, Mom. And you should get genetic counseling before you have another baby.” Courtesy aside, neither she nor any doctor we’ve seen could tell us how or why my children lost their hearing.

It has often been believed that Mondini hearing loss is congenital (some medical websites still claim that) – that children are born with Mondini due to an “insult” in the 7th week of gestation. But with large vestibular aqueduct syndrome (LVAS), it’s been recognized that hearing loss occurs later, which is how it happened with my three kids.[2] We can point to specific events that were likely triggers to the progression of hearing loss in the older two. I’m uncertain about Roo’s trigger because the loss occurred slowly and with fluctuation. Like Rheumatoid Disease, the cause of deafness is much more complicated than people imagine, including multiple genetic combinations and various environmental triggers that are scarcely understood. Answers will come for RD in the same way they are beginning to come for LVAS and Mondini: by considering what patients actually experience.

Rheumatoid Awareness Day is just a week away – February 2.

This year patients and organizations across the U.S. and in other countries are observing the second ever awareness day for RD. For updates on RPF sponsored Awareness Day events – click here. If you have a blog of any kind, please join our special blog carnival – What Would Rheumatoid Awareness Mean to You?

Recommended reading

FOOTNOTES
1 Worley S. Will Biomarkers Be Next Leap Forward in RA? Managed Care [Internet]. 2013 Aug [cited 2014 Jan 26]. Available from: http://www.managedcaremag.com/archives/2013/8/will-biomarkers-be-next-leap-forward-ra
2 Bauman N. Large Vestibular Aqueduct Syndrome (LVAS). Center for Hearing Loss Help [Internet]. 2002 Jun [cited 2014 Jan 26]. Available from: http://www.hearinglosshelp.com/articles/lvas.htm

EDIT 12:22pm: My good friend and colleague Robert West has taken strong exception to the views of Dr. Robinson quoted in this article. As a genetics professor, Dr. West states that cancer and RD are both polygenic. Although Dr. Robinson is a well qualified Stanford professor, I’m not able to spend the time necessary today to investigate his statement. The point of this post, that discovering causes, triggers, treatments, and cures is very complex, remains the same. I have invited Dr. West to elaborate on the comments page and I hope that discussion will continue, with the aim being to increase awareness of the complexity of RD and the need for increased research.

Kelly O'Neill Young

Kelly O'Neill (formerly Kelly Young) has worked over 10 years as an advocate helping patients to be better informed and have a greater voice in their healthcare. She is the author of the best-selling book Rheumatoid Arthritis Unmasked: 10 Dangers of Rheumatoid Disease. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. She is the president of the Rheumatoid Patient Foundation. Through her writing and speaking, she builds a more accurate awareness of rheumatoid disease (RD) aka rheumatoid arthritis (RA) geared toward the public and medical community; creates ways to empower patients to advocate for improved diagnosis and treatment; and brings recognition and visibility to the RA patient journey. In addition to RA Warrior, she writes periodically for newsletters, magazines, and websites. There are over 60,000 connections of her highly interactive Facebook page. You can also connect with Kelly by on Twitter or YouTube, or LinkedIn. She created the hashtag: #rheum. Kelly is a mother of five, longtime home-schooler, NASA enthusiast, and NFL fan. She has lived over thirteen years with unrelenting RD. See also https:/rawarrior.com/kelly-young-press/

10 thoughts on “Genetics & Rheumatoid Disease: More Complicated Than Cancer?

  • January 27, 2014 at 8:42 am
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    I was diagnosed with RA 2010 was on research for
    Awhile then taken off put on enbrel then taken
    Off and put on humira. They took DNA test but
    I was not given the results. Also I do not
    Know what medicine I was given. I walk on tread
    Mill at the YMCA 3 miles 3 times a week. I get
    Out of breath but keep going, legs hurt, but it
    Okay because it took a long time for doctors
    To find it and it took a naturalpath to know what
    To look for. Why??? I went from August. 2009
    To January 2010 finally went to natural path and
    Fifteen minutes had results. There is so much to
    This story so walking May or may not be the best
    Thing but mind over matter hope it keeps working
    For me.

    Reply
  • January 27, 2014 at 11:06 am
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    This is one of the more frustrating issues of being a PRD – that it’s complicated and we don’t have answers. Symptoms and how you feel are a reality, you learn to deal with them, however difficult it may be. When you search for solid answers, there are few. You ask a question and get a list of possibilities, conflicting answers, a shrug of the shoulders or just simply ignored. It’s like throwing a stack of papers in the air, waiting for them to fall and then being told to pick one.

    I am so glad we are pushing forward with the patient story. So glad to have a Foundation that represents and speaks for me, the patient. Hopefully, one day.

    Reply
  • January 27, 2014 at 11:54 am
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    Kelly, you’re simply amazing !!! Truly amazing !!! As a professional in the field of deafness and a fellow RD sufferer, I am continually amazed at your keen intellect coupled with tremendous compassion.

    May you have a blessed and productive 2014. May you find a combination of treatments that improves your quality of life as we all wait for a cure !!!!

    We are all graced with your care and continued commitment. Thank you for working with us, the medical community, and the public, tirelessly, for a better understanding and treatment of RD

    xo
    Sally

    Reply
  • January 27, 2014 at 12:08 pm
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    I’ve often thought that there has been a rather specific pattern to how my disease “flares” and how it has progressed. Through patient stories here and via an online support group I am in, I have found that my progression/symptoms/general story and patterns mirrors a just a few peoples experiences. While the debilitating pain is universal to all peoples experiences, there seems to be only a few people that experience things the same way I do. When I read these I usually exclaim “Yes, exactly!”

    Reply
  • January 27, 2014 at 4:14 pm
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    I recently participated in a research study through the local university, and one of the questions they asked was who else in my family had rheumatoid disease. I told them no one. They asked who else had an auto-immune issue. I told them no one. Nothing. I am one of those with absolutely no family history that we can trace back to the last several generations. (Of course when I first started asking my aunts and uncles, I was told “Oh yeah, grandma had that in her hip! Lol!) I am convinced that at 48, mine was brought on by hormonal changes, and I am hopeful that when those calm down, maybe my disease will go into remission. In cases though where it is genetic, it seems like we should be able to find the cause, and then the cure. We need to keep pushing for research! Thanks for your efforts Kelly!!

    Reply
  • January 27, 2014 at 4:30 pm
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    Kelly,
    I don’t have an issue with the vast majority of the content in this post, but as a regular RA Warrior reader, and also a geneticist by training, it’s only fair to warn you that the title you’ve chosen is inconsistent with the entire state of current cancer genetics. In this post, you’ve relied on a single comment made by a Stanford rheumatologist, who does himself a disservice by broadcasting his lack of familiarity with present-day cancer biology and genetics.

    The statement made by Dr. Robinson, also found in reference 1 is: “In cancer, a single genetic biomarker can completely guide treatment because that single gene is causing the disease.” But in fact, cancer is a very heterogeneous disease, both within and between patients, whether of the same tissue origin or not. About the only example of a cancer being due to single gene is that of chronic myelogenous leukemia (CML), which in almost every patient carrying this disease involves a fusion between BCR and ABL genes. As a single gene cancer, it’s highly treatable, by one of the very first magic bullet drugs on the market, Gleevec. But CML is the exception, not the rule, and as more and more cancers have been studied, most recently by genomic technologies, it’s clear that most cancers have multiple “driver” genes responsible for their tumor-causing behavior. Worse, they can mutate continually during their lifetime, meaning primary and metastatic cells may differ genetically, creating havoc for oncologists trying to treat them.

    I provide only a single reference to illustrate this point, but it is a gold-standard example of similar findings made by multitudinous labs around the world over the past decade:

    “Discovery and saturation analysis of cancer genes across 21 tumour types” by Eric Lander and colleagues, NATURE 505: 495 – 501. In the following sentence one can gain an appreciation of the significant heterogeneity in cancer types:

    “A total of 334 gene x tumour-type pairs were found by our analysis to
    be significantly mutated. These 334 pairs involve 224 distinct genes.
    The number of genes detected per tumour type varied considerably
    (range of 1–58), with 7 types having fewer than 10 genes and 2 (breast
    and endometrial) having more than 30 (Fig. 2, Supplementary Fig. 5
    and Table 1). The specific genes differed substantially across tumour
    types, although some pairs of tumour types showed clear similarity,
    such as lung squamous cancer and head and neck squamous cancer.”

    The bottom line is that, given such vast genetic heterogeneity, the vast majority of cancer patients will require a completely individualized approach to their treatment, making personalized medicine in oncology a very distant dream.

    That said, your present title “Genetics & Rheumatoid Disease: More Complicated Than Cancer” is inaccurate at best, and one which most, if not all, oncologists (as well as cancer patients) would find insulting. To be sure, RA genetics is complex; I’ve written about it as you’ve cited, both as a guest post at RA Warrior and on my own blog (http://bit.ly/1f3FbLg). But by almost any scientist’s definition of “complicated”, RA is not more complicated than cancer; both rely on a full understanding of human biology, physiology, and genetics. In fact, the exact opposite might be true. If funding at the level of cancer biology had been provided to rheumatologists to solve RA, we may have found by now that RA genetics is LESS complicated than cancer. At this point, both are complex, so to make any such comparison is really unjustified and futile.

    Perhaps the most disturbing fact to come out of this post is that a rheumatologist employed at a world-class academic medical research institution would make such an erroneous statement to begin with, with its concomitant ramifications on the RD community.

    – Bob

    Reply
    • May 13, 2014 at 4:33 pm
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      If you can not convince anyone with clear precise logic baffle them with bull shit. Right doc.

      Reply
  • February 5, 2014 at 11:53 am
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    It shouldn’t be “Us versus Them”. Both RA an CA are terrible, debilitating diseases. Both deserve research and attention to ways of predicting predisposition to development and finding treatments that actually help.

    Reply
  • March 28, 2014 at 11:25 am
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    As the youngest of 6 children, it’s taken a long time to learn that at least 3 of us have had autoimmune diseases: brother with psoriatic arthritis, sister with fibromyalgia, and my own rheumatoid arthritis. At least 5 of us didn’t/don/t tolerate statin drugs….and there’s more. At the very least, I hope our children and grandchildren will be met with some concern, perhaps getting earlier care for the possible genetic issues.

    Reply
  • May 13, 2014 at 4:31 pm
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    Has anyone ever wondered why doctors can cure nothing. Not a thing. they can give antibiotics to fight infections but other than that they cure absolutely nothing. A few of the conditions they can not cure and there are hundreds more. Alzheimers, arthritis,migraines,heart disease,cancer,ibs,chrons,parkinsons,diabetes,osteoporosis,and many many more like aids,etc.Why is it that they treat everything while curing nothing. Is it the fact that a cured patient is a former patient.

    Reply

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