COMT genotype associated with treatment related cognitive deficits (chemobrain)!

[Lani]

Seems a simple saliva test can tell whether one has the Val gene variation associated with chemobrain development

Might help those deciding whether or not to have chemo when benefit questionable

Hopefully in the future they might be able to tell which chemoagents cause/do not cause specific chemobrain associated with specific gene variations of COMT

ABSTRACT: Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors
[Cancer]

Background: Recent attention has focused on the negative effects of chemotherapy on the cognitive performance of cancer survivors. The current study examined modification of this risk by catechol-O-methyltransferase (COMT) genotype based on evidence in adult populations that the presence of a Val allele is associated with poorer cognitive performance.

Methods: Breast cancer survivors treated with radiotherapy (n = 58), and/or chemotherapy (n = 72), and 204 healthy controls (HCs) completed tests of cognitive performance and provided saliva for COMT genotyping. COMT genotype was divided into Val carriers (Val+; Val/Val, Val/Met) or COMT-Met homozygote carriers (Met; Met/Met).

Results: COMT-Val+ carriers performed more poorly on tests of attention, verbal fluency, and motor speed relative to COMT-Met homozygotes. Moreover, COMT-Val+ carriers treated with chemotherapy performed more poorly on tests of attention relative to HC group members who were also Val+ carriers.

Conclusions: The results suggest that persons treated with chemotherapy for breast cancer who also possess the COMT-Val gene are susceptible to negative effects on their cognitive health. This research is important because it strives to understand the factors that predispose some cancer survivors to more negative quality-of-life outcomes.

[SoCalGal]

Lani I want to give this info to a local doc who would be interested. Where is the info from? Do you have a link/site?
Thanks so very much!! Flori

[Jackie07]

Hi Flori,

I think this is it:

Cancer. 2010 Nov 8. [Epub ahead of print]
Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors.

Small BJ, Rawson KS, Walsh E, Jim HS, Hughes TF, Iser L, Andrykowski MA, Jacobsen PB.
School of Aging Studies, University of South Florida, Tampa, Florida.
Abstract

BACKGROUND: Recent attention has focused on the negative effects of chemotherapy on the cognitive performance of cancer survivors. The current study examined modification of this risk by catechol-O-methyltransferase (COMT) genotype based on evidence in adult populations that the presence of a Val allele is associated with poorer cognitive performance.
METHODS: Breast cancer survivors treated with radiotherapy (n = 58), and/or chemotherapy (n = 72), and 204 healthy controls (HCs) completed tests of cognitive performance and provided saliva for COMT genotyping. COMT genotype was divided into Val carriers (Val+; Val/Val, Val/Met) or COMT-Met homozygote carriers (Met; Met/Met).
RESULTS: COMT-Val+ carriers performed more poorly on tests of attention, verbal fluency, and motor speed relative to COMT-Met homozygotes. Moreover, COMT-Val+ carriers treated with chemotherapy performed more poorly on tests of attention relative to HC group members who were also Val+ carriers.
CONCLUSIONS: The results suggest that persons treated with chemotherapy for breast cancer who also possess the COMT-Val gene are susceptible to negative effects on their cognitive health. This research is important because it strives to understand the factors that predispose some cancer survivors to more negative quality-of-life outcomes. Cancer 2010. © 2010 American Cancer Society.

PMID: 21061339 [PubMed - as supplied by publisher]

[imdavidson]

Lani and Jackie,

Thanks so much for the information and for all of the resources you provide on this forum.

As you may know, I try to stay pretty current on this topic of "chemo brain," but for some reason, I never received a press release on this particular study so I'm really grateful to you for mentioning it here.

I read the abstract and then contacted the lead author who very kindly sent me the full-text of the article which includes a discussion section about the limitations of the study. And there are several. Still, the research looks promising and so I asked him these questions:

1) Are you recommending that cancer patients request this test prior to starting treatment?

2) If so, should they and their doctors make treatment decisions based on the outcome of this test?

And this was his response: "I do not think that it is appropriate for persons to be tested for the COMT genotype. As you will see in the Discussion of our paper, we specifically indicate that we do not believe that our results should alter clinical treatment practices, but they do provide information concerning the nature of cognitive deficits among persons who have been treated for breast cancer."

So even though this type of test is not yet a reliable predictor of who will experience cognitive impairment, it still moves the science forward. That's good news.

And by the way, there have been other studies that have looked at how genetic alleles affect cognitive function in cancer patients. One that we discuss at length in our book was by Sloan-Kettering researcher Tim Ahles. He and his team found that people who carry an allele called, "E4" may be at higher risk for developing both Alzheimer's disease and cognitive problems from chemotherapy. Those findings also are still experimental and require further study.

All the best,

Idelle Davidson

[Lani]

I think the answer is always "we can't at this time recommend this be done in a
clinical setting" because they have not yet done prospective clinical trials in a large population to validate their findings"

Even once that is accomplished, and it takes years, they are hesitant to say that clinical procedure should be changed as malpractice suits are based on "standard of care"

"gold standards" change slowly.

The test is not widely available, has not be validated as accurate between labs and hasn't be validated in a large population as giving information sufficiently accurately to change treatment protocols.

EVEN if this turns out to be a wonderful biomarker for prevention of chemobrain, they have to look at what the alternatives are ie, whether it will alter treatment--and as their are no non-chemo containing regimens yet approved for her2+ bc it will probably take until there are (and then some) for these findings to change the way her2+ bc is treated

I hope some trials for non-chemo based regimens, which have to compare the new regimen vs. chemo+ one targeted treatment regimen will measure their patients COMT levels of those in both regimens to see if those who otherwise might have been predisposed to chemo brain got to avoid it by having the purely targeted regimen

Such trials will be costly (two targeted agents) and take time..perhaps in the meantime they will get to understand more about whether all chemos' chemobrain are related this gene or only some. If the chemo culprit is also being used vs other cancers, maybe the answer will come from research into people being treated for those.

[Jackie07]

In the meanwhile, exercise, exercise, exercise...

I'm glad researchers are paying attention to the cognitive issues. Seems the cause of many health problems can now be traced down to the genetic level.

My late Mother-in-law and several of her female cousins living in the same community all developed cognitive problems in their late 70's. They share the same body type, life style, and similar health problems. Everyone passed away around their 82nd birthday - including her mother and her uncle... [Alcohol and/or tabaco use and diabetes status did not seem to make any difference.]

[imdavidson]

You're so right. Even if this test and others like it eventually become the gold standard in identifying who will experience cognitive problems, there's still the issue of "what's the alternative," since there may not be, as you said, cognitively safe drug choices anyway.

But on the positive side, such a test may help validate what people are going through and it may help patients' families understand what's going on so that they're more accepting.

And about exercise, I'm right with you on that!

[imdavidson]

Lani, I was trying to contact you but you're not set up to receive messages. Is there a way to reach you? Perhaps you could message me?