Germline PKHD1 mutations are protective against colorectal cancer

Christopher J. Ward, Yanhong Wu, Ruth A. Johnson, John R. Woollard, Eric J. Bergstralh, Mine S. Cicek, Jason Bakeberg, Sandro Rossetti, Christina M. Heyer, Gloria M. Petersen, Noralene M. Lindor, Stephen N. Thibodeau, Peter C. Harris, Vicente E. Torres, Marie C. Hogan, Lisa A. Boardman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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).

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalHuman genetics
Issue number3
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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