caa a22 4500 445861622 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00439-011-0950-8 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0950-8 Germline PKHD1 mutations are protective against colorectal cancer [Elektronische Daten] [Christopher Ward, Yanhong Wu, Ruth Johnson, John Woollard, Eric Bergstralh, Mine Cicek, Jason Bakeberg, Sandro Rossetti, Christina Heyer, Gloria Petersen, Noralene Lindor, Stephen Thibodeau, Peter Harris, Vicente Torres, Marie Hogan, Lisa Boardman] 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). Springer-Verlag, 2011 Ward Christopher Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Wu Yanhong Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut Johnson Ruth Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut Woollard John Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Bergstralh Eric Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA aut Cicek Mine Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut Bakeberg Jason Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Rossetti Sandro Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Heyer Christina Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Petersen Gloria Division of Health Science Research, Mayo Clinic, Rochester, MN, USA aut Lindor Noralene Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA aut Thibodeau Stephen Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut Harris Peter Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Torres Vicente Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Hogan Marie Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut Boardman Lisa Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA aut Human Genetics Springer-Verlag 129/3(2011-03-01), 345-349 0340-6717 129:3<345 2011 129 439 https://doi.org/10.1007/s00439-011-0950-8 text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0950-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ward Christopher Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Wu Yanhong Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Johnson Ruth Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Woollard John Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Bergstralh Eric Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Cicek Mine Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Bakeberg Jason Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Rossetti Sandro Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Heyer Christina Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Petersen Gloria Division of Health Science Research, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Lindor Noralene Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Thibodeau Stephen Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 700 1- Harris Peter Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Torres Vicente Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Hogan Marie Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA aut NATIONALLICENCE 700 1- Boardman Lisa Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/3(2011-03-01), 345-349 0340-6717 129:3<345 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer