tag:blogger.com,1999:blog-6235733697979948062.post6650029441809259236..comments2024-03-19T00:33:30.191-07:00Comments on our brain tumor cocktails and stories: The methylenetetrahydrofolate reductase (MTHFR) variant c.677C>T influences overall survival of patients with glioblastoma multiformeStephen Whttp://www.blogger.com/profile/00777652648990108253noreply@blogger.comBlogger8125tag:blogger.com,1999:blog-6235733697979948062.post-83707188975565460472017-01-24T23:54:00.840-08:002017-01-24T23:54:00.840-08:00https://clinicaltrials.gov/ct2/show/NCT01891747
A...https://clinicaltrials.gov/ct2/show/NCT01891747<br /><br />A Phase I/II Study of High-dose L-methylfolate in Combination With Temozolomide and Bevacizumab in Recurrent High Grade GliomaStephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-50433144225347142292017-01-21T10:41:53.261-08:002017-01-21T10:41:53.261-08:00Of course it's also possible a person could in...Of course it's also possible a person could inherit one variant of the MTHFR gene (c.677C>T for example) from one parent, and a different variant (for example c.1298A>C) from the other parent. I'm not sure whether your testing was looking for other variants besides c.677C>T.Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-32661991834510576522017-01-21T10:26:13.135-08:002017-01-21T10:26:13.135-08:00You're saying he is heterozygous for the varia...You're saying he is heterozygous for the variant, meaning he has one copy of the normal C allele and once copy of the variant T allele. His MTHFR activity would therefore not be as impaired as someone homozygous for the variant (having 2 copies of the mutant T allele). <br /><br />An individual homozygous for the 677C>T variant (having two copies of the impaired T allele) is much more likely to have clinical complications than someone heterozygous for the variant (having one impaired T allele and one normal C allele). In a case like this (such as your brother's case) the normal C allele could compensate for the impaired activity of the T allele. This is also reflected in the GBM retrospective study in which patients homozygous for the 677C>T variant (two copies of the T allele, or TT or T/T genotype) had worse median survival, but patients heterozygous for the variant (only one copy of the impaired T allele, or CT, or C/T genotype) had median survival similar to patients without the variant (two copies of the normal C allele, or CC genotype).<br /><br />In short, I'd expect L-methylfolate supplementation to be more important for someone with two mutant T alleles (homozygous for the variant) than someone with only one mutant T allele (heterozygous for the variant).<br /><br />"Homozygous mutations often increase methylfolate requirements compared with heterozygous mutations."<br />http://www.mthfrtreatment.com/Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-74867154405933591452017-01-20T23:32:01.054-08:002017-01-20T23:32:01.054-08:00He has the C/T variant, "greatly reduced acti...He has the C/T variant, "greatly reduced activity" or heterozygous" phenotype. The common 677C to T genetic variant has reduced catalytic activity and is associated with a low tissue concentration of folate. The resulting impairment of DNA methylation could then affect many physiologic processes. Hyperhomocysteinemia is not an uncommon finding and is known to lead to DNA hypomethylation and altered gene expression, many can be corrected by administration of folate. Anonymoushttps://www.blogger.com/profile/17975914286433675214noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-70624529995715557942017-01-20T23:20:19.950-08:002017-01-20T23:20:19.950-08:00Mine was the C/C "normal" and his was th...Mine was the C/C "normal" and his was the C/T "greatly reduced activity" phenotype. Anonymoushttps://www.blogger.com/profile/17975914286433675214noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-72838716645246511122017-01-20T21:37:10.594-08:002017-01-20T21:37:10.594-08:00Also note that L-methylfolate is the same thing as...Also note that L-methylfolate is the same thing as 5-methyltetrahydrofolate (5-MTHF) which was discussed in the previous post (click on the 5-MTHF label from the labels menu). This molecule is the normal end product of the MTHFR enzyme, which converts 5,10-methyleneTHF to 5-MTHF. I'm not aware of anyone on the blog taking L-methylfolate (5-MTHF) supplements as part of their GBM cocktail, but perhaps there is someone out there that has.Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-38364455737123918892017-01-20T21:17:45.935-08:002017-01-20T21:17:45.935-08:00Was he heterozygous or homozygous for the MTHFR c....Was he heterozygous or homozygous for the MTHFR c.677C>T variant (was the variant found in only one or both copies of the gene)? The study shows that the greatest impact on survival is for patients homozygous for the c.677C>T variant (TT genotype). If only one copy of the gene was thus affected (CT genotype), median survival was the same as for those without the variant (CC genotype).Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-82094017962228807032017-01-20T20:08:06.438-08:002017-01-20T20:08:06.438-08:00There was some discussion of this same study here:...There was some discussion of this same study here:<br /><br />http://btcocktails.blogspot.com/2015/08/what-is-folinic-acid.html#comment-formStephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.com