Human Genetics

, Volume 129, Issue 3, pp 345–349

Germline PKHD1 mutations are protective against colorectal cancer

Authors

    • Division of Nephrology and HypertensionMayo Clinic
  • Yanhong Wu
    • Department of Laboratory Medicine and PathologyMayo Clinic
  • Ruth A. Johnson
    • Department of Laboratory Medicine and PathologyMayo Clinic
  • John R. Woollard
    • Division of Nephrology and HypertensionMayo Clinic
  • Eric J. Bergstralh
    • Division of Biomedical Statistics and InformaticsMayo Clinic
  • Mine S. Cicek
    • Department of Laboratory Medicine and PathologyMayo Clinic
  • Jason Bakeberg
    • Division of Nephrology and HypertensionMayo Clinic
  • Sandro Rossetti
    • Division of Nephrology and HypertensionMayo Clinic
  • Christina M. Heyer
    • Division of Nephrology and HypertensionMayo Clinic
  • Gloria M. Petersen
    • Division of Health Science ResearchMayo Clinic
  • Noralene M. Lindor
    • Department of Medical GeneticsMayo Clinic
  • Stephen N. Thibodeau
    • Department of Laboratory Medicine and PathologyMayo Clinic
  • Peter C. Harris
    • Division of Nephrology and HypertensionMayo Clinic
  • Vicente E. Torres
    • Division of Nephrology and HypertensionMayo Clinic
  • Marie C. Hogan
    • Division of Nephrology and HypertensionMayo Clinic
  • Lisa A. Boardman
    • Division of Gastroenterology and HepatologyMayo Clinic
Short Report

DOI: 10.1007/s00439-011-0950-8

Cite this article as:
Ward, C.J., Wu, Y., Johnson, R.A. et al. Hum Genet (2011) 129: 345. doi:10.1007/s00439-011-0950-8

Abstract

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).

Copyright information

© Springer-Verlag 2011