NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

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Kobe
Posts: 27
Joined: Wed Mar 01, 2017 10:29 am

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby Kobe » Wed Jun 14, 2017 7:29 am

I'm trying to gather as much information as I can. I love the idea of 6 treatments instead of 12. I also know fear jumps into the equation pretty fast so I'm trying to get the facts together so I can talk with my oncologist. I'm Stage 2bT4N0M0 and being treated at University of Connecticut Medical Center.

The article seems to only mention FOLFOX or CAPOX - not sure about 5-FU. Does anyone have information on 5-FU with this study?

behconsult - Do you happen to have links to any of the research articles you read? Where are you being treated? Did you do FOLFOX or 5-FU?

LPL - what are SNP's

kfgardella - my T4 sounds similar to yours and that's what put me in the higher risk category. I had 45 clear lymph nodes and clear margins with surgery. Where are you getting treated? I'd love to hear more details about how the discussion/decision went with your oncologist if you're okay sharing. Were you doing 5-FU or FOLFOX?

Thanks everyone :)

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LPL
Posts: 312
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby LPL » Wed Jun 14, 2017 8:15 am

Kobe wrote:
LPL - what are SNP's

Here is an explanation https://ghr.nlm.nih.gov/primer/genomicresearch/snp
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

Kobe
Posts: 27
Joined: Wed Mar 01, 2017 10:29 am

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby Kobe » Wed Jun 14, 2017 10:47 am

Thanks LPL - I'll read the article. It will be helpful to have that understanding when I get the results from 23andme

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LPL
Posts: 312
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby LPL » Wed Jun 14, 2017 2:06 pm

Hi Kobe, if this (your 23andme result) feels Interesting to you, and you have questions after getting your results. (You will need to now how to search your raw data to find SNPs of interest).
I'm here if I can be of assistance.
Kind regards /L
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

Kobe
Posts: 27
Joined: Wed Mar 01, 2017 10:29 am

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby Kobe » Wed Jun 14, 2017 2:44 pm

That's great - thanks. I just mailed it in on Monday so it will be a little while before I get the results.

Kobe
Posts: 27
Joined: Wed Mar 01, 2017 10:29 am

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby Kobe » Thu Jul 20, 2017 8:35 am

Hi LPL,

I got my 23andme results back and I just ran the raw data through livewello.com to interpret it. Livewello is interesting and for $20 the raw data gets read but to see everything you have to buy the premium subscription of $60 a year. I didn't know that when I paid the $20. There is data for 5-FU but its part of the subscription.

If you can share any information about which SNP's are useful so I can search them that would be great. This is a whole new language to learn :)

Thanks, Kobe

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LPL
Posts: 312
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby LPL » Thu Jul 20, 2017 9:27 am

Hi Kobe,
:wink: How did you know that I was just looking in to this for you today (have had family visiting for a week but they left this morning).
Have also found recent papers that was not published when I searched DH's 23andme raw data last year.
I will post later today (I hope) with a summary.
Yes genetics is for sure a new world with it's own language! You know how to search the raw data?
Kind regards /L
Last edited by LPL on Sat Jul 22, 2017 5:23 am, edited 1 time in total.
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

User avatar
LPL
Posts: 312
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby LPL » Thu Jul 20, 2017 11:29 am

Hi again Kobe,

I am pretending that you know how to search your raw data and how to interpret.

Disclamer: Please know that I am not an expert but this below is how I interpret what I have read.

Will start with this paper that I found the other day,
From (Sep 2016) Capecitabine Therapy and DPYD Genotype
https://www.ncbi.nlm.nih.gov/books/NBK3 ... rt=classic
It has info about 3 important DPYD SNPs and & rsid# are included. All 3 of them can be found in my 23andme raw data !
Direct link to a table in the paper https://www.ncbi.nlm.nih.gov/books/NBK3 ... objectonly

These are the SNPs
DPYD*2A rs3918290 Alleles G or A Risk allele A Note: 23andme Alleles C or T - Risk allele T*

DPYD*13 rs 55886062 Alleles T or G Risk allele G Note: 23andme Alleles A or C - Risk allele C*

(2846A>T) rs 67376798 Alleles A or T Risk allele T Note: 23andme Alleles A or T - Risk allele A*
("Note that the "A>T" term in the name used in the literature for this SNP can be confusing, since the gene is in reverse orientation to the chromosome strand on the reference genome." https://www.snpedia.com/index.php/Rs67376798
Plus see below
*

* = “Genes are read (transcribed) in either the forward or reverse direction, as numbered along the chromosome. If a new build comes along that flips a large segment of a chromosome, the gene direction will change. As a result, at different times, as well as in different publications or different databases, the same SNP can be defined as being on the forward (plus) or as being on the reverse (minus) strand. In terms of the nucleotides for that SNP, the pairing of A with T, and C with G, in the DNA double helix means that an A on the plus strand by definition is a T on the minus strand, and vice versa, and a C on the plus strand means a G on the minus strand (and vice versa).” “Companies follow their own protocols, which are often different. 23andMe currently reports all genotype data based on the plus strand of GRCh37, whether or not dbSNP defined the SNP as being on the plus strand (in that build or any other build); they explain this for their customers … here (https://customercare.23andme.com/hc/en- ... -Genotypes ).
This often leads to confusion since a 23andMe customer may see a genotype in their raw data that will not match the genotypes defined by dbSNP, in SNPedia, or in their Promethease report. This will most often happen when the StabilizedOrientation is minus. In these cases, the alleles need to be "flipped" to match:
A->T
T->A
C->G
G->C
” Reference: https://www.snpedia.com/index.php/Orientation

Links to Snpedia for these 3 SNPs for more research reading/info about them:
https://www.snpedia.com/index.php/Rs3918290
https://www.snpedia.com/index.php/Rs55886062
https://www.snpedia.com/index.php/Rs67376798
-------------

Here is another recent paper from 2017 that mention 5 SNPs, the first 3 are the same as the above. I have not looked/found rsid# for the last two yet.
Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe
https://bmcmedgenomics.biomedcentral.co ... 017-0283-0
For 5-FU toxicity, the frequency of DPYD*2A is low in all populations. It is almost non-existent in African-American and Japanese populations, and has frequency of 0.91% and 0.47% in Dutch and German populations respectively [26].”
“For 5-FU, 23andMe tests only for the *2A variant, but as 23andMe state on their website, further variants in the gene are associated with 5-FU toxicity. For example, recent studies have shown that DPYD*13, rs67376798, c.1679 T > G and c.1236G > A/HapB3 are also associated with 5-FU toxicity [28, 29, 30].



Kind regards /L
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

User avatar
LPL
Posts: 312
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: NEWS from ongoing ASCO 2017: shorter chemo for stage III OK

Postby LPL » Fri Jul 21, 2017 8:03 am

To Kobe,

Added info about the 2017 paper Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe that I linked to in my previous post.
That paper had a Reference (#30) a systematic review and meta-analysis of individual patient data, published in The Lancet Dec 2015. The summary of that review is:
DPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines.

So from reading that 2015 review plus the 2016 paper I linked to before Capecitabine Therapy and DPYD Genotype
- my interpretation is that these 4 SNPs are the most important:
DPYD*2A rs3918290
DPYD*13 c.1679T>G rs5588606
c.2846A>T rs67376798
these 3 above are mentioned in my previous post
plus
c.1236G>A/HapB3 that has the rsid# rs56038477
Note: Unfortunately My 23andme raw data says for rs56038477: “not genotyped”.
[I found the rs56038477 on this testing Lab’s web site (Their DPYD panel include 5 SNPs with rsid# info - 4 of them can be found in my 23andme raw data.]

Kobe, you mentioned MTHFR before. If you find it interesting to read more about that (and other genes) in connection with chemo side effects – this 2017 paper says: “Toxicity prevention of capecitabine-based chemotherapies may be improved by additional biomarkers linked to the regulation of DPD expression, such as miR-27a and more specifically MIR27A rs895819 polymorphism [39], or to polymorphisms in other genes related to capecitabine pharmacology, such as MTHFR, CDA, TYMS or ENOSF1 [40,41,42] that have been shown to be associated with capecitabine toxicity.

This was the info I had - I hope it can be of use for you.
Disclamer: Please remember that I am not an expert ! Just sharing my own notes with you.
Kind Regards /L
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets


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