Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer.
Br J Cancer
; 105(11): 1654-62, 2011 Nov 22.
Article
in En
| MEDLINE
| ID: mdl-22045187
ABSTRACT
BACKGROUND:
There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study.METHODS:
The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed.RESULTS:
MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C-1298C) and diplotypes (CA-TA and TA-TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response.CONCLUSION:
MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rectal Neoplasms
/
Methylenetetrahydrofolate Reductase (NADPH2)
/
Fluorouracil
/
Antimetabolites, Antineoplastic
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2011
Document type:
Article
Affiliation country:
United States