PURPOSE: Locally advanced rectal cancer is currently treated with pre-surgical radiotherapy and chemotherapy. Approximately one-half of patients obtain a relevant shrinkage/disappearance of tumour, with major clinical advantages. The remaining patients, in contrast, show no benefit and possibly need alternative treatment. To provide the best therapeutic option for each individual patient, predictive markers have been widely researched. This review was undertaken to evaluate recent progress made in this field. METHODS: A systematic literature search was performed using PubMed and Scopus database, focused on germ line gene polymorphisms as biomarkers and response and toxicity as outcomes. Because an exhaustive previous review was available describing findings up to 2008, we restricted our analysis to the last 5 years. RESULTS: Ten original research articles were found, reporting promising results for some candidate genes in drug metabolism (TYMS, MTHFR), DNA repair (XRCC1, OGG1, CCND1) and inflammation (SOD2, TGFB1)/immunity (IL13) pathways, but with no firm conclusion. All the studies had small sample size and were defined as exploratory. This review highlights pivotal molecular, clinical, genetic and statistical issues in the investigation of genetic polymorphisms as outcome predictors for rectal cancer and offers suggestions for future development. CONCLUSIONS: What emerges is a clear need for new proposals, especially in view of the increasing evidence for tumour-host and gene-gene interactions during anticancer treatment, together with stronger adherence to proper methodological requirements.
PURPOSE: Locally advanced rectal cancer is currently treated with pre-surgical radiotherapy and chemotherapy. Approximately one-half of patients obtain a relevant shrinkage/disappearance of tumour, with major clinical advantages. The remaining patients, in contrast, show no benefit and possibly need alternative treatment. To provide the best therapeutic option for each individual patient, predictive markers have been widely researched. This review was undertaken to evaluate recent progress made in this field. METHODS: A systematic literature search was performed using PubMed and Scopus database, focused on germ line gene polymorphisms as biomarkers and response and toxicity as outcomes. Because an exhaustive previous review was available describing findings up to 2008, we restricted our analysis to the last 5 years. RESULTS: Ten original research articles were found, reporting promising results for some candidate genes in drug metabolism (TYMS, MTHFR), DNA repair (XRCC1, OGG1, CCND1) and inflammation (SOD2, TGFB1)/immunity (IL13) pathways, but with no firm conclusion. All the studies had small sample size and were defined as exploratory. This review highlights pivotal molecular, clinical, genetic and statistical issues in the investigation of genetic polymorphisms as outcome predictors for rectal cancer and offers suggestions for future development. CONCLUSIONS: What emerges is a clear need for new proposals, especially in view of the increasing evidence for tumour-host and gene-gene interactions during anticancer treatment, together with stronger adherence to proper methodological requirements.
Authors: Thomas Armstrong; Graham Packham; Lindsay B Murphy; Adrian C Bateman; John A Conti; David R Fine; Colin D Johnson; R Christopher Benyon; John P Iredale Journal: Clin Cancer Res Date: 2004-11-01 Impact factor: 12.531
Authors: Huixiao Hong; Lei Xu; Jie Liu; Wendell D Jones; Zhenqiang Su; Baitang Ning; Roger Perkins; Weigong Ge; Kelci Miclaus; Li Zhang; Kyunghee Park; Bridgett Green; Tao Han; Hong Fang; Christophe G Lambert; Silvia C Vega; Simon M Lin; Nadereh Jafari; Wendy Czika; Russell D Wolfinger; Federico Goodsaid; Weida Tong; Leming Shi Journal: PLoS One Date: 2012-09-07 Impact factor: 3.240
Authors: M Gusella; S Giacopuzzi; L Bertolaso; A Zanoni; E Pezzolo; Y Modena; D Menon; P Paganin; J Weindelmayer; G Crepaldi; G De Manzoni; F Pasini Journal: Pharmacogenomics J Date: 2016-03-01 Impact factor: 3.550