Germline PKHD1 mutations are protective against colorectal cancer

Hum Genet. 2011 Mar;129(3):345-9. doi: 10.1007/s00439-011-0950-8. Epub 2011 Jan 28.


The autosomal recessive polycystic kidney disease (ARPKD) gene, PKHD1, has been implicated in the genesis or growth of colorectal adenocarcinoma, as a high level of somatic mutations was found in colorectal tumor tissue. To determine whether carriers of a single PKHD1 mutation are at increased risk of colorectal carcinoma, we assessed the prevalence of the commonest European mutation, T36M. First, we assayed a European cohort of ARPKD patients and found T36M was responsible for 13.1% of mutations. We then investigated two European cohorts with colorectal adenocarcinoma versus two control cohorts of similar age and gender. Screening for the most common PKHD1 mutation, T36M, we detected 15:3,603 (0.42%) controls versus 1:3,767 (0.027%) colorectal cancer individuals, indicating that heterozygous PKHD1 mutations are not a risk factor and are protective (p=0.0002). We also show that the carriage rate for PKHD1 mutations in the European population is higher than previous accepted at 3.2% (1:31 genomes).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Aged
  • Cohort Studies
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Female
  • Germ-Line Mutation*
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Receptors, Cell Surface / genetics*
  • Whites / genetics


  • PKHD1 protein, human
  • Receptors, Cell Surface