A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer

Jason B. Nikas, Janet T. Lee, Elizabeth D. Maring, Jill Washechek-Aletto, Donna Felmlee-Devine, Ruth A. Johnson, Thomas C. Smyrk, Patrick S. Tawadros, Lisa A. Boardman, Clifford J Steer

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


An important determinant of the pathogenesis and prognosis of various diseases is inherited genetic variation. Single-nucleotide polymorphisms (SNPs), variations at a single base position, have been identified in both protein-coding and noncoding DNA sequences, but the vast majority of millions of those variants are far from being functionally understood. Here we show that a common variant in the gene MTHFR [rs1801133 (C>T)] not only influences response to neoadjuvant chemoradiotherapy in patients with rectal cancer, but it also influences recurrence of the disease itself. More specifically, patients with the homozygous ancestral (wild type) genotype (C/C) were 2.91 times more likely (291% increased benefit) to respond to neoadjuvant chemoradiotherapy {95% CI: [1.23, 6.89]; P=0.0150} and 3.25 times more likely (325% increased benefit) not to experience recurrence of the disease {95% CI: [1.37, 7.72]; P=0.0079} than patients with either the heterozygous (C/T) or the homozygous mutation (T/T) genotype. These results identify MTHFR as an important genetic marker and open up new, pharmacogenomic strategies in the treatment and management of rectal cancer.

Original languageEnglish (US)
Pages (from-to)3231-3240
Number of pages10
JournalAmerican Journal of Cancer Research
Issue number10
StatePublished - 2015


  • Genetic variation
  • MTHFR single nucleotide polymorphism
  • Personalized medicine
  • Rectal cancer
  • Recurrence of rectal cancer
  • Response to chemoradiotherapy


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