Human Genetics

, Volume 129, Issue 3, pp 345–349

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
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

Authors and Affiliations

  • Christopher J. Ward
    • 1
  • Yanhong Wu
    • 3
  • Ruth A. Johnson
    • 3
  • John R. Woollard
    • 1
  • Eric J. Bergstralh
    • 4
  • Mine S. Cicek
    • 3
  • Jason Bakeberg
    • 1
  • Sandro Rossetti
    • 1
  • Christina M. Heyer
    • 1
  • Gloria M. Petersen
    • 5
  • Noralene M. Lindor
    • 6
  • Stephen N. Thibodeau
    • 3
  • Peter C. Harris
    • 1
  • Vicente E. Torres
    • 1
  • Marie C. Hogan
    • 1
  • Lisa A. Boardman
    • 2
  1. 1.Division of Nephrology and HypertensionMayo ClinicRochesterUSA
  2. 2.Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA
  3. 3.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  4. 4.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  5. 5.Division of Health Science ResearchMayo ClinicRochesterUSA
  6. 6.Department of Medical GeneticsMayo ClinicRochesterUSA