Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis

Pharmacogenomics J. 2016 Jun;16(3):249-65. doi: 10.1038/tpj.2015.46. Epub 2015 Jun 30.


Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Chemotherapy, Adjuvant
  • Chi-Square Distribution
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Genetic Association Studies
  • Genotype
  • Germ-Line Mutation*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Neoadjuvant Therapy*
  • Odds Ratio
  • Pharmacogenomic Variants*
  • Phenotype
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Risk Factors
  • Thymidylate Synthase / genetics
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics


  • Biomarkers, Tumor
  • KRAS protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • TYMS protein, human
  • Thymidylate Synthase
  • Proto-Oncogene Proteins p21(ras)