Pharmacogenetic Analysis in Neoadjuvant Chemoradiation for Rectal Cancer: High Incidence of Somatic Mutations and their Relation with Response

Balboa, Emilia; Duran, Goretti; Lamas, María Jesús; Caamaño, Antonio Gómez; Celeiro-Muñoz, Catuxa; López, Rafael; Carracedo, Ángel; Barros, Francisco

doi:10.2217/pgs.10.51

Cited by 32 publications

(25 citation statements)

References 83 publications

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“…We excluded three studies in which the data could not be estimated and whose authors were unreachable (Monzo et al, 2007;McLeod et al, 2010;Lee et al, 2013). Another additional study was excluded because patients were treated without oxaliplatin-based chemotherapy (Moreno et al, 2006) and patients in one study were treated with chemoradiotherapy (Balboa et al, 2010). By contrast, one article consisted of two independent studies, and studies included in this article were treated as separate studies (MartinezBalibrea et al, 2008).…”

Section: Search Results and Study Selectionmentioning

confidence: 99%

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Qian

Liu²,

Pei³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups.

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Section: Search Results and Study Selectionmentioning

confidence: 99%

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Qian

Liu²,

Pei³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…This is the first study investigating the role of pharmacogenetics in 5-FU toxicity in rectal cancer while two studies have already looked at the influence of these genetic markers on drug response (Terrazzino et al , 2006; Balboa et al , 2010). Terrazzino et al (2006) showed that patients with the MTHFR 667T–1298A haplotype had a lower tumour regression rate compared with other haplotypes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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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.

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“…If the gene mutation associated with poor DNA-repair ability, which should lead to increased sensitivity to irradiation, and may be increase radiotherapy efficacy, even though could be induced radiotherapy toxicity. Several studies assessed the impact of DNA repair gene polymorphisms on radiotherapy efficacy, especially XRCC-family genes (XRCC1 and XRCC3) and ERCCfamily genes (ERCC1 and ERCC2) polymorphisms (Balboa et al, 2010). Although there are many studies reported that XRCC1, XRCC3, ERCC1 and ERCC2 genes common polymorphisms influence on individual differences of therapeutic efficacy of radiotherapy for rectal cancer, but the results are often not unified (Balboa et al, 2010;Lamas et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies assessed the impact of DNA repair gene polymorphisms on radiotherapy efficacy, especially XRCC-family genes (XRCC1 and XRCC3) and ERCCfamily genes (ERCC1 and ERCC2) polymorphisms (Balboa et al, 2010). Although there are many studies reported that XRCC1, XRCC3, ERCC1 and ERCC2 genes common polymorphisms influence on individual differences of therapeutic efficacy of radiotherapy for rectal cancer, but the results are often not unified (Balboa et al, 2010;Lamas et al, 2012). For example, Lamas et al found X-ray-repair-cross complementing 1 (XRCC1) rs25487 was significantly associated with the response of radiotherapy in rectal cancer while other studies presented not consistent (Balboa et al, 2010;Cecchin et al, 2010;Grimminger et al, 2010;Lamas et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Guo

Yang²,

Pei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: : A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

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Pharmacogenetic Analysis in Neoadjuvant Chemoradiation for Rectal Cancer: High Incidence of Somatic Mutations and their Relation with Response

Cited by 32 publications

References 83 publications

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

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

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

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