Germline PKHD1 mutations are protective against colorectal cancer

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

Research output: Contribution to journalArticle

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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).

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalHuman Genetics
Volume129
Issue number3
DOIs
StatePublished - Mar 2011

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Germ-Line Mutation
Colorectal Neoplasms
Mutation
Autosomal Recessive Polycystic Kidney
Adenocarcinoma
Mutation Rate
Genome
Growth
Population
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Germline PKHD1 mutations are protective against colorectal cancer. / Ward, Christopher J.; Wu, Yanhong; Johnson, Ruth A.; Woollard, John R.; Bergstralh, Eric J.; Cicek, Mine; Bakeberg, Jason; Rossetti, Sandro; Heyer, Christina M.; Petersen, Gloria M; Lindor, Noralane Morey; Thibodeau, Stephen N; Harris, Peter C; Torres, Vicente; Hogan, Marie C; Boardman, Lisa Allyn.

In: Human Genetics, Vol. 129, No. 3, 03.2011, p. 345-349.

Research output: Contribution to journalArticle

Ward CJ, Wu Y, Johnson RA, Woollard JR, Bergstralh EJ, Cicek M et al. Germline PKHD1 mutations are protective against colorectal cancer. Human Genetics. 2011 Mar;129(3):345-349. https://doi.org/10.1007/s00439-011-0950-8
Ward, Christopher J. ; Wu, Yanhong ; Johnson, Ruth A. ; Woollard, John R. ; Bergstralh, Eric J. ; Cicek, Mine ; Bakeberg, Jason ; Rossetti, Sandro ; Heyer, Christina M. ; Petersen, Gloria M ; Lindor, Noralane Morey ; Thibodeau, Stephen N ; Harris, Peter C ; Torres, Vicente ; Hogan, Marie C ; Boardman, Lisa Allyn. / Germline PKHD1 mutations are protective against colorectal cancer. In: Human Genetics. 2011 ; Vol. 129, No. 3. pp. 345-349.
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