Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability

Abstract

The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.

Pharmacogenetic Predictors of Outcome in Patients with Stage II and III Colon Cancer Treated with Oxaliplatin and Fluoropyrimidine-Based Adjuvant Chemotherapy

“…In accordance with our data, some studies show a negative effect on survival or response for the 677T allele (13,37). However, other authors show no influence of MTHFR rs1801133 C>T genotype (12,26,38,39) and others again show a positive effect of the T allele (11,37,40). Our results are not consistent with in vitro findings that suggest that patients with the T/T genotype would have reduced MTHFR activity compared with those with C/C and C/T genotypes, potentiating the antitumoral activity of fluoropyrimidines.…”

“…More recently, the necessary interactions between tumor and host in the oncological process have raised questions about how the individual genomic biology influences cancer progression and response to chemotherapy, consequently generating a great amount of critical data. In the last few years, several genetic polymorphisms within genes involved in the metabolism, transport, and detoxification of fluoropyrimidines and oxaliplatin have been considered in an attempt to optimize treatment in patients with colon cancer (10)(11)(12)(13)(14)(15)(16)(17)(18), but, up to now, their clinical applications remain limited. Furthermore, numerous variants have been identified in genes related to the DNA-repair complex, angiogenesis, and other relevant pathways that may alter their expression and/or activity, thereby causing interindividual differences in tumor recurrence capacity and chemoresistance (18)(19)(20)(21)(22).…”

Red blood cell folate and plasma folate are not associated with risk of incident colorectal cancer in the Women's Health Initiative observational study

“…An additional limitation is that we were not able to assess whether the lack of associations observed in the WHI would be modified by genetic variation in folate metabolizing enzymes ( e.g ., methylenetetrahydrofolate reductase). At least one recent study shows an important relationship between methylenetetrahydrofolate reductase variation and CRC risk . Further research pooling data and specimens from large cohort studies is needed to have sufficient power to address the question.…”

“…At least one recent study shows an important relationship between methylenetetrahydrofolate reductase variation and CRC risk. 41 Further research pooling data and specimens from large cohort studies is needed to have sufficient power to address the question. Finally, as with all observational studies, residual confounding may have occurred from variables that were either unmeasured or measured with poor precision in the WHI-OS.…”

MTHFR polymorphisms in primary varicose vein disorder

“…The second MTHFR polymorphism A1298C lies in the C-terminal end of the enzyme, the S-adenosylmethionine regulatory domain, and may result in a decrease of 40% in enzyme activity of the variant genotype ( Weisberg et al, 2002 ). Both polymorphisms have been found to be implicated in colon cancer risk and the response to 5-FU chemotherapy, since MTHFR is implicated in the FU metabolism ( Fernández-Peralta et al, 2010 , Delgado-Plasencia et al, 2013 ). Also, these polymorphisms have been previously implicated in thrombotic disease ( Milio et al, 2008 , Wilmanns et al, 2011 ).…”