title: A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer.
abstract: 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.
authors.affiliation: Genomix Inc. Minneapolis, MN, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Nikas
authors.affiliation: Department of Surgery, University of Minnesota Minneapolis, MN, USA.
authors.forename: Janet T
authors.initials: JT
authors.lastname: Lee
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota Minneapolis, MN, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Maring
authors.affiliation: Department of Gastroenterology & Hepatology, Mayo Clinic Rochester, MN, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Washechek-Aletto
authors.affiliation: Department of Gastroenterology & Hepatology, Mayo Clinic Rochester, MN, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Felmlee-Devine
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Johnson
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Department of Surgery, University of Minnesota Minneapolis, MN, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tawadros
authors.affiliation: Department of Gastroenterology & Hepatology, Mayo Clinic Rochester, MN, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Boardman
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota Minneapolis, MN, USA ; Department of Medicine, University of Minnesota Minneapolis, MN, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Steer
keywords: MTHFR single nucleotide polymorphism; Rectal cancer; genetic variation; personalized medicine; recurrence of rectal cancer; response to chemoradiotherapy