Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

Thomas, Fabienne; Motsinger‐Reif, Alison A.; Hoskins, Janelle M.; Dvorak, Anne; Roy, Snigdha; Alyasiri, A.; Myerson, Robert J.; Fleshman, James W.; Tan, Benjamin; McLeod, Howard L.

doi:10.1038/bjc.2011.442

Cited by 49 publications

(42 citation statements)

References 48 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SNP-based toxicity risk has been studied using both candidate gene and genome-wide association approaches [95,96]. To date, the use of SNPs as mucositis risk predictors has been evaluated in a relatively small number of studies [95,[97][98][99][100][101]. Most of these studies are not confirmed and are predominantly associated with metabolic pathways of a small number of drugs.…”

Section: Advances In Mucosal Injury Risk Predictionmentioning

confidence: 99%

Emerging evidence on the pathobiology of mucositis

Al‐Dasooqi

Sonis

Bowen

et al. 2013

Support Care Cancer

168

View full text Add to dashboard Cite

Background Considerable progress has been made in our understanding of the biological basis for cancer therapyinduced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. Methods Panel members reviewed the biomedical literature on mucositis pathobiology published between January 2005 and December 2011.Results Recent research has provided data on the contribution of tissue structure changes, inflammation and microbiome changes to the development of mucositis. Additional research has focused on targeted therapyinduced toxicity, toxicity clustering and the investigation of genetic polymorphisms in toxicity prediction. This review paper summarizes the recent evidence on these aspects of mucositis pathobiology. Conclusion The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity.

show abstract

Section: Advances In Mucosal Injury Risk Predictionmentioning

confidence: 99%

Emerging evidence on the pathobiology of mucositis

Al‐Dasooqi

Sonis

Bowen

et al. 2013

Support Care Cancer

168

View full text Add to dashboard Cite

show abstract

“…9, 11, 14, 16–21 However, few studies have examined this association in patients with rectal cancer. 22, 23 …”

Section: Introductionmentioning

confidence: 99%

Gene polymorphisms predict toxicity to neoadjuvant therapy in patients with rectal cancer

Duldulao

Lee

Nelson

et al. 2012

Cancer

View full text Add to dashboard Cite

Background Toxicity from neoadjuvant chemoradiation therapy (NT) increases morbidity and limits therapeutic efficacy in patients with rectal cancer. Our objective was to determine whether specific polymorphisms in genes associated with rectal cancer response to NT correlate with NT-related toxicity. Methods One hundred thirty-two patients with locally advanced rectal cancer were treated with NT followed by surgery. All patients received 5-fluorouracil (5-FU) and radiation (RT), and 80 patients also received modified FOLFOX-6 (mFOLFOX-6) chemotherapy. Grade ≥3 adverse events (AEs) that occurred during 5-FU/RT and 5-FU/RT+mFOLFOX-6 were recorded. Pretreatment biopsies and normal rectal tissue were collected from all patients. DNA was extracted and screened for 22 polymorphisms in 17 genes associated with response to NT. Polymorphisms were correlated with treatment-related Grade ≥3 AEs. Results Overall 27 of 132 (20%) patients had Grade ≥3 AEs; 24 of 132 (18%) patients had Grade ≥3 AEs during 5-FU/RT, 9 of 80 (11%) patients had Grade ≥3 AEs during mFOLFOX-6, and 6 (5%) patients had Grade ≥3 AEs during both 5-FU/RT and mFOLFOX-6. Polymorphisms in XRCC1, XPD, and TP53 were associated with Grade ≥3 AEs during NT (p<0.05). Specifically, the XRCC1 Q399R and XPD K751Q polymorphisms were associated with increased toxicity to 5-FU/RT (p<0.05), and the TP53 R72P polymorphism was associated with increased toxicity to mFOLFOX-6 (p=0.008). Conclusion Specific polymorphisms in XRCC1, XPD, and TP53 are associated with increased toxicity to NT in rectal cancer. Polymorphism screening may help tailor treatment for patients by selecting therapies with the lowest risk of toxicity thus increasing patient compliance.

show abstract

“…We reviewed the titles and abstracts of all the 146 articles and excluded 80; full texts and data integrity were also reviewed and 59 articles were further excluded. Finally, seven clinical cohort studies with a total of 815 CRC patients met our inclusion criteria for qualitative data analysis (Marcuello et al, 2006;Ruzzo et al, 2008;Braun et al, 2009;Glimelius et al, 2011;Thomas et al, 2011;Budai et al, 2012;van Huis-Tanja et al, 2013). Publication years of the eligible studies ranged from 2006 to 2013.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Currently, common polymorphisms (1298 A > C and 677 C/T) in the MTHFR gene have been reported to be closely associated with the toxicity and clinical responses of irinotecan-based chemotherapy in CRC patients (Glimelius et al, 2011;van HuisTanja et al, 2013). Nevertheless, contradictory results were also reported in many other studies (Braun et al, 2009;Thomas et al, 2011). Therefore, we performed this metaanalysis to evaluate the effects of common polymorphisms in the MTHFR gene on the toxicity and clinical responses of irinotecan-based chemotherapy in CRC patients.…”

Section: Introductionmentioning

confidence: 97%